The number of men ages 35-49 who father children has increased 40 percent since 1980 while the number of fathers under 30 has fallen 20 per cent

Research finds sperm quality drops, genetic problems rise as men age
Sabin Russell, Chronicle Medical Writer

Tuesday, June 6, 2006


With a lineup of Bay Area men at their disposal, Lawrence Livermore scientists have deflated yet another cherished male fantasy -- that sperm quality resists the ravages of age.

In fact, the genetic quality of sperm deteriorates as time goes by.

The Livermore analysis of sperm samples from men ages 22-80 found a gradual but steady increase in the percentage of genetic mutations over time, raising the risk of infertility and of fathering children with genetic abnormalities.

Until now, men had some reason to think their sperm could stand the test of time: Sperm are generated continuously in the testes from sexual maturity through old age. A woman's supply of eggs, on the other hand, is produced before birth. Because the eggs age with her, the risk for some chromosomal anomalies such as Down syndrome linked to egg defects increase with a pregnant woman's age.

The study found that although an older man's sperm does not increase the likelihood of Down syndrome, other genetic conditions such a dwarfism can be passed on with greater frequency by older men.

"There is a reproductive consequence to delaying fatherhood,'' said Andrew Wyrobek, a senior staff biophysicist at the Livermore National Laboratory, and lead author of the study published today in the Proceedings of the National Academy of Sciences.

It is an issue of increasing relevance as men as well as women defer parenthood to a later age in the United States. The number of men ages 35-49 who father children has increased 40 percent since 1980, according to Wyrobek, while the number of fathers under 30 has fallen 20 percent. .................................



Co-lead author Barbara Eskenazi said: "We know that women have a biological time clock. Our research suggests that men too have a biological time clock - only it is different. Men seem to have a gradual rather than an abrupt change in fertility and in the potential to produce viable healthy offspring."


But it found a steady increase in the amount of broken DNA strands as the age of the subjects increased. This genetic damage can translate into fertility problems, pregnancy failures and an increase in some genetic diseases.

As the men aged, the researchers found that the number of genetic mutations that can cause dwarfism increased in the sperm with the age of the men -- at a rate of about 2 percent per year.

Wyrobek stressed that, although the trend toward genetic deterioration with age was clear, there were disparities in sperm quality among the men within each age group. Even in the oldest cohort, there were some men with few genetic mutations in their sperm, while others had multiple abnormalities.

Michael Moore's "Sicko" and the dire state of US healthcare

News Conference
William Maher and John Graham, two men who traveled with Moore to Cuba to receive medical care for health problems related to their work at ground zero, on Friday at a news conference criticized the U.S. health care system. At the news conference, held by Rep. Jose Serrano (D-N.Y.), the men said they traveled to Cuba after they were unable to receive care in the U.S.

Maher noted that many workers have died from injuries and illnesses related to their work at ground zero. "For those who are still suffering, hopefully we can get the help to them that they have not been able to get," he said. Graham, a disabled carpenter who has been uninsured since 2005, spoke of his difficulties receiving treatment in the U.S. for lung and kidney problems, injuries to his esophagus and stomach, and other ailments. He said that since receiving treatment in Cuba, "I know a lot more about my medical condition now than I did before."

Serrano said at the news conference that ground zero workers have "health conditions that have cost them employment, health conditions that have put them in difficult family situations, health conditions that have totally changed their lives forever." He added, "Our government... talks about how much we respect them" but we have, "in fact, ignored them" (Hayasaki, Los Angeles Times, 5/26).

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There are images of patients dumped back on the streets of Los Angeles by local hospitals. In the most controversial segment, Moore takes Sept. 11 workers with respiratory problems to Cuba to receive care that eluded them at home. And he takes on politicians who accept millions from insurers and drug manufacturers.

Moore's team approached a number of California health and consumer groups, including the nurses association, the Foundation for Taxpayer and Consumer Rights and Health Access California, for individual stories about patients who were denied care or otherwise suffered at the hands of insurers, pharmaceutical companies or other health business interests.

"Rumor is they literally had hundreds, if not thousands, of stories to go through," said Anthony Wright, executive director of Health Access California, a consumer advocacy group.

Wright, whose group supports universal health care, said he hopes the movie draws attention to insurance industry practices that should be reformed or made illegal. For example, he pointed to lawsuits against Blue Cross of California and other insurers by consumers who were retroactively denied coverage after submitting claims.

THE AGE OF THE FATHER KEN BIRNBAUM IS OF GREAT CONCERN 63 is MUCH TOO OLD BECAUSE OF SPERM DNA MUTATIONS FOR ONE THING

60-Year-Old Woman Who Just Gave Birth To Twin Boys Says, “Age Has Been Redefined”


The psychologist who gave birth to twin boys at age 60 said Thursday she was on a mission to let women know they have choices.

“It’s really basically about women and empowerment,” Frieda Birnbaum told NBC’s “Today” show.

Frieda Birnbaum, who underwent in-vitro fertilization last year at a South African clinic that specializes in older women, gave birth by Caesarean section on Tuesday at Hackensack University Medical Center.

“I don’t feel like I went through a lot of trauma during delivery or even through the process of being pregnant,” Frieda Birnbaum said.

The hospital said she was the nation’s oldest mother of twins.

“Age has been redefined,” Frieda Birnbaum said.

She and her husband, Ken, a New York City attorney, have been married for 38 years and have three other children — sons ages 33 and 6 and a daughter, 29.

The couple wanted another child closer in age to their youngest son, and Frieda Birnbaum’s husband said it was his idea for his wife to become pregnant instead of adopting.

“I couldn’t be happier about the way it worked out,” Ken Birnbaum told “Today.”

Their daughter has said she worries about Frieda Birnbaum taking care of the twins when they’re in their teens and she’s in her late 70s — concerns dismissed by Frieda Birnbaum on Thursday.

“I hope I’m a role model for my daughter, that when she gets older that she can make her own decisions based on who she is rather than what society dictates,” she said. (I think biology has something to do with it too…not just society!)

She said that people who consider new motherhood at her age inappropriate “need to get ready for what’s coming up in our society.”

The couple plan to take their sons home on Saturday.

(I may catch a lot of slack for this, but I think a woman choosing to have a child at 60 is incredibly selfish. I could see adopting at 60 a little differently, but for her to go out of her way to insist on having a child at 60 is bizarre. Sorry, but how is having children at 60 female empowerment!? It is simply female insanity! Women are not meant to have children at 60, as her having to go to a South African clinic for in-vitro fertilization attests.)

Oh well…..congratulations!

Source

"A DIRECT CAMPAIGN FOR FATHERS TO COMPLETE THEIR FAMILIES BEFORE THE AGE OF 35 MAY HAVE AN EFFECT IN THE PREVENTION OF DOMINANT MUTATIONS SPAIN '88

Am J Med Genet. 1988 Dec;31(4):845-52. Links
Prevalence of dominant mutations in Spain: effect of changes in maternal age distribution.Martinez-Frias ML, Herranz I, Salvador J, Prieto L, Ramos-Arroyo MA, Rodriguez-Pinilla E, Cordero JF.
Estudio Colaborativo Espanol de Malformaciones Congenitas (ECEMC), Facultad de Medicina, Universidad Complutense, Madrid, Spain.

We studied the birth prevalence of autosomal dominant mutations in Spain and estimated how a decrease in maternal age distribution may lead to reduction in dominant mutations. The data were collected by the Estudio Colaborativo Espanol de Malformaciones Congenitas from April, 1976, to December, 1985. Among 553,270 liveborn infants monitored during the period, 66 infants with autosomal dominant conditions were identified. These included Apert, Crouzon, Hay-Wells, Treacher-Collins, Robinow, Stickler, Adams-Oliver, and the blepharophimosis syndromes, achondroplasia, cleidocranial dysostosis, and thanatophoric dysplasia. The overall rate of autosomal dominant conditions was 1.2 per 10,000 liveborn infants. Thirteen (20%) had an affected relative, and 52 (79%) had a negative family history. One case was excluded because of insufficient family data. The rate of autosomal dominant mutations was 0.9 per 10,000 liveborn infants, or 47 per 1 million gametes. A reduction in the maternal age distribution of mothers age 35 years and older from the current 10.8% to 4.9%, as in Atlanta, Georgia, would reduce the rate of Down syndrome in Spain by 33% and through a change in parternal age distribution may lead to a reduction in dominant mutations of about 9.6%. This suggests that a public health campaign to reduce older maternal age distribution in Spain may also lead to a reduction in dominant mutations and emphasizes the potential that a direct campaign for fathers to complete their families before age 35 years may have a small, but measurable, effect in the primary prevention of dominant mutations.

PMID: 3239577 [PubMed - indexed for MEDLINE]

THESE HEART DEFECTS INCREASE WITH PATERNAL AGE VSD VENTRICULAR SEPTAL DEFECTS, ATRIAL SEPTAL DEFECTS AND PATENT DUCTUS ARTERIOSUS

Teratology

Volume 50, Issue 1 , Pages 80 - 84
Published Online: 8 Jun 2005

Paternal age and the risk of congenital heart defects
Andrew F. Olshan, Ph.D. 1 2 *, Patricia G. Schnitzer 1, Patricia A. Baird 3
1Department of Epidemiology, School of Public Health, University of North, Carolina, Chapel Hill, North Carolina 27599
2University of North Carolina Birth Defects Center, Chapel Hill, North Carolina 27599
3Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada


*Correspondence to Andrew F. Olshan, Department of Epidemiology, CB# 7400 McGarvran-Greenberg Hall, Unversity of North Carolina, Chapel Hill, NC 27599

Abstract
The effect of paternal age on the risk of birth defects among affspring is less well studied than the effect of maternal age, with few comprehensive epidemiologic studies having been conducted. Advanced paternal age has been shown to be associated with an increase in new dominant mutations that result in particular congenital anomalies. The relationship between paternal age more common birth defects, for example, cardiac defects, has not been as extensively evaluated. Therefore, a total of 4, 110 cases of congenital heart defects was identified from the British Columbia Health Surveillance Registry. Matched controls were obtained from the birth files of British Columbia for the years 1952-1973. Prevalence odds ratios for paternal age, adjusted for maternal age and other factors, were estimated for 8 cardiac defect groups.
A suggestive general pattern of increasing risk with increasing age among cases (excluding chromosomal anomalies) relative to controls was found for ventricular septal defects (VSD), atrial septal defects (ASD), and patent ductus arteriosus (PDA). In addition, an increased risk among men younger than 20 yr was found for VSD and ASD. These findings are consistent with the results of some previous epidemiologic studies. Based on the results of the study it is estimated that for cardiac defects such as VSD, approximately 5% of cases may be due to advanced paternal age (>35yr), Possibly through dominant mutations. © 1994 Wiley-Liss, Inc.



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Received: 22 March 1994; Accepted: 23 March 1994
Digital Object Identifier (DOI)

33.7 mean age in maternal grandfathers at birth of mother of studied boys with DUCHENNES MUSCULAR DYSTROPHY 29.5 mean age in controls

WHERE WERE YOU JERRY LEWIS ON THIS ALL THOSE YEARS YOU COULD HAVE DONE SOME GOOD BY WARNING MEN TO FATHER BEFORE 33.


Am J Med Genet. 1980;7(1):27-34. Links
Frequency of new mutants among boys with Duchenne muscular dystrophy.Bucher K, Ionasescu V, Hanson J.
Haldane's rule states that one-third of the cases of an X-linked recessive lethal should represent new mutations. This rule is derived under the assumptions that there is equilibrium between mutation and selection, that mutation rates in ova and sperm are equal, and that heterozygous and homozygous normal women have the same fitness. To test this rule for Duchenne muscular dystrophy (DMD), we have examined the mothers of 55 boys with DMD (16 familial and 39 isolated cases) and classified them as carriers or noncarriers on the basis of measures of ribosomal protein synthesis (RPS). Of the 55 mothers, only nine (16.4%) are classified as noncarriers, a figure significantly different from the expected one-third. When the analysis is limited to the 39 mothers of isolated cases, 23.1% (9/39) are classified as noncarriers, still significantly different than expected under Haldane's rule. Violation of any of the assumptions under which Haldane's rule is derived could lead to deviations from the expected one-third new mutants. We find the most likely explantation to be a higher male than female mutation rate. This is supported also by the finding that maternal grandfathers in whom a mutation occurred had higher mean age at birth of the carrier daughter (33.7 +/- 1.6) than did the general population or intrapedigree controls (29.5 +/- 1.3).

SPERM DONORS CUT-OFF AGE IS 35TH BIRTHDAY AT THIS CRYOBANK, S. AFRICAN BANK CUT-OFF 30TH BIRTHDAY, ARE THEY AWARE ?

Donor Standards

Our donors are recruited from the Northwest US. Most of our donors are either starting, currently involved with, or have finished their higher education at the time of their participation in our donor program. All donors are between 18 and 35 years of age in order to minimize age related genetic abnormalities. All donors are frozen in very limited quantities in order to guarantee that the number of pregnancies created from any one donor are limited. We stop further sales to new clients at 10 reported successes. Although all donor histories are reviewed to provide you with donors that should give you a great chance of concieving a healthy and normal baby, there is of course no way to guarantee such an outcome. As all donor family histories will present with their own unique positive and negative attributes, we encourage all clients to review donor information thoroughly prior to purchase and use of specimens.

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MORE SCHIZOPHRENIA IN OFFSPRING AT 35 AND ABOVE IS FOUND IN ALL STUDIES

1: Eur Psychiatry. 2007 Jan;22(1):22-6. Epub 2006 Dec 4. Links
Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring.Wohl M, Gorwood P.
INSERM U675, 16 rue Henri Huchard 75018 Paris, France.
BACKGROUND: A link between older age of fatherhood and an increased risk of schizophrenia was detected in 1958. Since then, 10 studies attempted to replicate this result with different methods, on samples with different origins, using different age classes. Defining a cut-off at which the risk is significantly increased in the offspring could have an important impact on public health. METHODS: A meta-analysis (Meta Win) was performed, assessing the mean effect size for each age class, taking into account the difference in age class references, and the study design. RESULTS: An increased risk is detected when paternal age is below 20 (compared to 20-24), over 35 (compared to below 35), 39 (compared to less than 30), and 54 years old (compared to less than 25). Interestingly, 35 years appears nevertheless to be the lowest cut-off where the OR is always above 1, whatever the age class reference, and the smallest value where offspring of fathers below or above this age have a significantly different risk of schizophrenia. CONCLUSION: No threshold can be precisely defined, but convergent elements indicate ages below or above 35 years. Using homogeneous age ranges in future studies could help to clarify a precise threshold.

AN INCREASING INCIDENCE OF SPORADIC WILM'S TUMOR WITH INCREASING PATERNAL AGE WAS FOUND

1: Br J Cancer. 1993 Apr;67(4):813-8. Links
Wilms' tumour and parental age: a report from the National Wilms' Tumour Study.Olson JM, Breslow NE, Beckwith JB.
Department of Biostatistics, University of Washington, Seattle 98195.

Age distributions of parents at birth of patients registered in the National Wilms' Tumour Study were compared to those of the general population. An increasing incidence of sporadic Wilms' tumour with increasing paternal age was found, with a relative risk of 2.1 of tumour in children of fathers over 55 compared to children of fathers younger than 20. A similar effect for maternal age was found, with a relative risk of 1.4 in children of mothers over 40 compared to children of mothers younger than 20. The maternal age effect was much weaker among patients registered later in the study; in the later, more completely ascertained cohort, paternal age appears to be the major contributor to the parental age effect. Little difference in paternal age distribution was found between patients with bilateral and unilateral tumour and between male and female patients. In contrast, patients with reported associated congenital anomalies, patients with evidence of nephrogenic rests, and patients with early or late age-of-onset of tumour had parents who were, on average, substantially older than the remainder. These findings lend support to the idea that many Wilms' tumours result from new germline mutations. Further, the histologic composition of such tumours may be sufficiently distinct as to provide a valuable diagnostic indicator of the etiology of these tumours.

PMID: 8385980 [PubMed - indexed for MEDLINE]

DEREK FISHER'S DAUGHTER OPERATED ON FOR RETINOBLASTOMA -

The procedure went well, although subsequent treatment awaits Tatum. The Jazz beat the Golden State Warriors in overtime, with her father making a key contribution that will long be remembered in the team's playoff lore.


Tatum, the little daughter of Utah Jazz point guard Derek Fisher has been diagnosed with a type of cancer called retinoblastoma

It is being reported that the little 10-month-old daughter of Utah Jazz point guard Derek Fisher is in hospital with a very serious medical condition.

Tatum Fisher has recently been diagnosed with a type of cancer known as retinoblastoma, which is a cancer of the eye. Treatment options include, removal of the eye, or a combination of chemotherapy and surgery.

The little girl's condition was first identified by her mother who noticed a weird reflection of light coming from her eye. A few doctor visits and a pediatrician visit later the family learned of the troubling diagnosis.

Doctors at New York Presbyterian Hospital performed a procedure on the baby girl in which they injected chemotherapy drugs directly into the tumor hoping to shrink it. If three such surgeries do not shrink the tumor to the point where it can be removed, then the little girl will lose her eye altogether.

“My wife and I definitely plan to try and help as many people as we can,” Fisher said. “I don’t know how we’ll be able to at this point. If there’s a treatment out there, they should be able to get it. Some people can’t afford to get it. Some people don’t have the resources.

"They've done nine cases," Fisher said. "(In) one case the child's arterial structure wasn't strong enough, but the other eight kids that had the treatment, all of their tumors have reduced in size."

Twin brother of Tatum, little Drew Fisher was also examined for signs of the condition however he is perfectly healthy.

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Parental age in retinoblastoma
Journal Human Genetics
Publisher Springer Berlin / Heidelberg
ISSN 0340-6717 (Print) 1432-1203 (Online)
Issue Volume 20, Number 1 / MarcFeingold1 and Jean Frézal1

(1) Unité de Recherche de Génétique Médicale (I.N.S.E.R.M.-h, 1973
Category Short Communications
DOI 10.1007/BF00280877
Pages 59-62
Subject Collection Biomedical and Life Sciences
SpringerLink Date Tuesday, November 30, 2004



Short Communications
Parental age in retinoblastoma
Catherine Pellié1, Marie-Louise Briard1, Josué U 12), Hôpital des Enfants Malades, 149, rue de Sèvres, 75730 Paris Cedex 15
Received: 12 June 1973

Summary In a review of information on 444 patients with sporadic retinoblastoma, a correlation with increased fathers'age was demonstrated and no correlation with was found in the unilateral form. These data favor the hypothesis that the bilateral form is caused by a germinal mutation and the unilateral form is due to somatic mutations.


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1: Int J Epidemiol. 2001 Dec;30(6):1428-37. Links
Comment in:
Int J Epidemiol. 2001 Dec;30(6):1438-9.
Case-control study of parental age, parity and socioeconomic level in relation to childhood cancers.Dockerty JD, Draper G, Vincent T, Rowan SD, Bunch KJ.
Childhood Cancer Research Group, Department of Paediatrics, University of Oxford, 57 Woodstock Road, Oxford OX2 6HJ, UK.

BACKGROUND: Parental ages, parity, and social class have been found in some studies to be associated with particular childhood cancers. Further investigation is warranted because of conflicting findings, biases, and the need to test specific hypotheses. METHODS: A case-control study was conducted (England and Wales, ages 0-14 years). Cases were ascertained from the National Registry of Childhood Tumours, and were born and diagnosed during 1968-1986. Birth record controls were matched 1:1 to cases on date of birth, sex and area. Information on variables of interest for both groups came from birth records. In all, 10 162 pairs could contribute to matched analyses. RESULTS: The odds ratio (OR) for retinoblastoma resulting from assumed new germ cell mutations among children of fathers aged > or =45 years was 3.0 (95% CI : 0.2-41.7). The risk of childhood acute lymphoblastic leukaemia (ALL) was significantly higher among children of older mothers and fathers, and significant trends with increasing mothers' (P < 0.001) and fathers' (P = 0.002) ages were found. There was a strong and significant protective effect of increasing parity on risk of childhood ALL. The adjusted OR for parity of > or =5 (versus 0) was 0.5 (95% CI : 0.3-0.8). Children in more deprived communities had a lower risk of ALL; but this was not significant after confounders were allowed for. There was no significant effect of social class based on parental occupation on ALL risk, but the numbers were small in those analyses. CONCLUSIONS: The associations between ALL and parental ages did not disappear when children with Down syndrome were excluded, suggesting an additional explanation beyond known links. The strong ALL association with parity may be because of an unknown


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1: Ophthalmic Epidemiol. 2000 Dec;7(4):285-91. Links
Parental age in Indian patients with sporadic hereditary retinoblastoma.Sivakumaran TA, Ghose S, Kumar H, A S, Kucheria K.
Division of Genetics, Department of Anatomy, Dr. Rajendra Prasad Centre for Ophthalmic Science, All India Institute of Medical Sciences, New Delhi, India.

There is a consistent correlation between sporadic hereditary retinoblastoma and parental age. It has been proven beyond doubt that the birth rank is correlated with parental age. In the present study, a test for the effect of birth rank was performed in order to assess the risk of developing retinoblastoma with increased parental age. The study of the effect of birth rank showed a significant association between sporadic retinoblastoma (bilateral and unilateral) and late para, indicating that fresh germline mutations must have taken place in some of the sporadic cases. An investigation of the effect of birth rank on familial cases, obtained from published papers and our own series, showed that familial retinoblastoma is significantly associated with early para, suggesting early parental age. Further analysis of the mean paternal and maternal ages of sporadic cases (bilateral and unilateral) showed that the mean paternal age of sporadic bilateral (sporadic hereditary) cases was higher than that of sporadic unilateral cases (p<0.05). No such correlation was seen with mean maternal age. Thus, the present study shows that a high paternal age may be associated with sporadic bilateral (sporadic hereditary) retinoblastoma.

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1: Am J Ophthalmol. 1990 Dec 15;110(6):605-9. Links
Parental age in sporadic hereditary retinoblastoma.DerKinderen DJ, Koten JW, Tan KE, Beemer FA, Van Romunde LK, Den Otter W.
Department of Pathology, Academisch Ziekenhuis Utrecht, The Netherlands.Of 104 children with sporadic hereditary retinoblastoma born between 1945 and 1970, we studied the age of their parents at the birth and compared this age with the mean age of parents at the birth of their children during the same period in The Netherlands. The mean age of fathers at the birth of their children with sporadic hereditary retinoblastoma (33.7 years) was significantly higher than the mean age of fathers at the birth of their children in the general population (32.5 years) (P less than .05, one sided). Similarly, the mean age of mothers at the birth of their children with sporadic hereditary retinoblastoma (31.2 years) was significantly higher than the mean age of mothers at the birth of their children in the general population (29.5 years) (P less than .05, one sided). We further analyzed this parental age factor by measuring the relative risk of age groups and comparing the incidence of sporadic hereditary retinoblastoma in the various parental age groups with the incidence of sporadic hereditary retinoblastoma in the total population. Mothers 35 years of age or older had a relative risk of 1.7 to have a child with sporadic hereditary retinoblastoma compared with mothers in the population in general (P = .006, one sided). Similarly, fathers 50 years of age or older had a relative risk of 5.0 to have a child with sporadic hereditary retinoblastoma compared with fathers in the population in general (P = .04, one sided). No parental age effect was found in children with nonhereditary retinoblastoma. We conclude that a high paternal and a high maternal age are significant risk factors for sporadic hereditary retinoblastoma.


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Br J Cancer. 1993 Apr;67(4):813-8. Links
Wilms' tumour and parental age: a report from the National Wilms' Tumour Study.Olson

WILM'S TUMOR INCIDENCE INCREASES WITH INCREASING PATERNAL AGE


JM, Breslow NE, Beckwith JB.
Department of Biostatistics, University of Washington, Seattle 98195.

Age distributions of parents at birth of patients registered in the National Wilms' Tumour Study were compared to those of the general population. An increasing incidence of sporadic Wilms' tumour with increasing paternal age was found, with a relative risk of 2.1 of tumour in children of fathers over 55 compared to children of fathers younger than 20. A similar effect for maternal age was found, with a relative risk of 1.4 in children of mothers over 40 compared to children of mothers younger than 20. The maternal age effect was much weaker among patients registered later in the study; in the later, more completely ascertained cohort, paternal age appears to be the major contributor to the parental age effect. Little difference in paternal age distribution was found between patients with bilateral and unilateral tumour and between male and female patients. In contrast, patients with reported associated congenital anomalies, patients with evidence of nephrogenic rests, and patients with early or late age-of-onset of tumour had parents who were, on average, substantially older than the remainder. These findings lend support to the idea that many Wilms' tumours result from new germline mutations. Further, the histologic composition of such tumours may be sufficiently distinct as to provide a valuable diagnostic indicator of the etiology of these tumours.

PMID: 8385980 [PubMed - indexed for MEDLINE]

GENETIC RISK FACTORS EATING DISORDERS PATERNAL AGE INVOLVED?

Source: Michigan State University
Date: May 12, 2007
More on: Mental Health Research, Nutrition Research, Disorders and Syndromes, Sleep Disorders, Obesity, Psychiatry

Genetic Risk Factors For Eating Disorders Discovered
Science Daily — Until recently, it was generally believed that eating disorders such as anorexia nervosa and bulimia nervosa resulted solely from environmental influences such as peer pressure and certain perceived expectations of society.



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But research at Michigan State University has found that there are genetic risk factors at work as well. The research of Kelly Klump, an MSU associate professor of psychology, published in the May issue of Psychological Medicine, indicates that the origin of eating disorders has biological roots, similar to how bipolar disorder and schizophrenia are thought to have biological causes.

Anorexia, Greater Maternal and Paternal Age at the Time of Birth

Psychosomatic Medicine Vol. 36, No. 1 (Jan.-Feb. 1974)
Anorexia Nervosa:
Demographic and Clinical Features in 94 Cases
KATHERINE A. HALMI, MD
A comprehensive chart study was made of numerous clinical and demographic features in 94
patients with anorexia nervosa. Unlike other large series, this survey included the pediatric age
group. A significantly greater maternal and paternal age at time of the patient's birth and a
greater incidence of both low and high birth weights compared with the general population was
found. A relatively high occurrence of premorbid feeding problems was present. Anxiety and
obsessive-compulsive traits were frequent premorbid symptoms. Precipitating events were
identified more frequently in patients with a greater age at onset of illness. Characteristic
behavior noted during the course of this illness is described.




The mothers' age at time of the patients'
birth was significantly greater (p < .001,
Kolmogorov-Smirnov goodness fit test)
than that for national control mothers (14)
or Iowa control mothers2 (Fig. 1). Also,
the fathers' age at the time of the patients'
birth was significantly greater (p < .05,
Kolmogorov-Smirnov goodness-of-fit test)
than that of national control fathers (15)
(Fig. 2). A significantly higher mothers'
age at the time of probands' birth compared
to that of Swedish control mothers
was also reported by Theander (1). Kay
and Leigh (11) did not analyze their data
statistically, but nonetheless stated that
youthfulness or advanced age of mothers
at the patients' birth appeared unimportant.


SUMMARY
Significant demographic characteristics
found in this survey of the hospital
records of 94 anorexia patients include a
greater maternal and paternal age at time
of the probands' birth and a greater
incidence of both low and high birth
weights than in the general population.
Unlike other large series of anorexia
nervosa patients, this survey included the
pediatric age group. This would explain
the relatively high incidence, 8%, of onset
of illness prior to age 10.

Germline Mutations FOR CENTRAL NERVOUS SYSTEM CANCERS THE EFFECT OF PATERNAL AGE WAS FOUND TO BE SIGNIFICANT

1: Curr Neurol Neurosci Rep. 2007 May;7(3):200-7.Update on the management of familial central nervous system tumor syndromes.Hottinger AF, Khakoo Y.
Departments of Neurology and Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Khakooy@mskcc.org.

Hereditary central nervous tumor syndromes are a varied group of conditions that include neurofibromatosis type 1 and 2, tuberous sclerosis, Von Hippel-Lindau disease, and Cowden, Turcot, and Gorlin syndromes. The responsible genes have been identified in most of these disorders. These genes typically act as tumor suppressor genes, maintain normal cellular function and homeostasis, and regulate cell growth and differentiation. Familial central nervous system tumors are mostly inherited as autosomal dominant traits and involve germline mutations. Neoplastic development occurs when a somatic mutation inactivates the second allele. These patients also present unique challenges for their management. This review highlights the clinical manifestations, molecular genetics, pathophysiology, and current treatment options of these disorders with a focus on neuro-oncologic manifestations of the diseases.

PMID: 17488585 [PubMed - in process]



1: Int J Epidemiol. 2006 Dec;35(6):1495-503. Epub 2006 Sep 28. Links
Parental age and risk of childhood cancers: a population-based cohort study from Sweden.Yip BH, Pawitan Y, Czene K.
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 171 77 Stockholm, Sweden.BACKGROUND: Frequent germ line cells mutations were previously demonstrated to be associated with aging. This suggests a higher incidence of childhood cancer among children of older parents. A population-based cohort study of parental ages and other prenatal risk factors for five main childhood cancers was performed with the use of a linkage between several national-based registries. METHODS: In total, about 4.3 million children with their parents, born between 1961 and 2000, were included in the study. Multivariate Poisson regression was used to obtain the incidence rate ratios (IRR) and 95% confidence interval (CI). Children <5 years of age and children 5-14 years of age were analysed independently. RESULTS: There was no significant result for children 5-14 years of age. For children <5 years of age, maternal age were associated with elevated risk of retinoblastoma (oldest age group's IRR = 2.39, 95%CI = 1.17-4.85) and leukaemia (oldest age group's IRR = 1.44, 95%CI = 1.01-2.05). Paternal age was significantly associated with leukaemia (oldest age group's IRR = 1.31, 95%CI = 1.04-1.66). For central nervous system cancer, the effect of paternal age was found to be significant (oldest age group's IRR = 1.69, 95%CI = 1.21-2.35) when maternal age was included in the analysis. CONCLUSION: Our findings indicate that advanced parental age might be associated with an increased risk of early childhood cancers.

WASSINK SAYS AGE IS NOT A FACTOR IN THIS FINDING OF A MUTATION'/ABNORMALITY IN THE FATHER'S SPERMATAGONIA-IS THIS TRUE?

"De novo point mutations in such genes could explain the advanced paternal age association that has been reported for autism13. There is no evidence, however, that the risk of a de novo CNV is related to the age of either parent
Arthur L. Beaudet in his paper, Nature Medicine - 13, 534 - 536 (2007)
doi:10.1038/nm0507-534
Autism: highly heritable but not inherited
Arthur L Beaudet

U-I researchers find genetic link to autism
Monday, May 7, 2007, 4:11 PM
By Darwin Danielson
University of Iowa researchers have found a genetic mutation that contributes to a brain disorder that inhibits a person's ability to communicate and develop social relationships. Dr. Thomas Wassink says the finding involving autism was part of a larger study of families which have children with the disorder.

Wassink says there was one family where they found "a piece of a chromosome missing in the middle of a really interesting gene, in two girls with autism from this family."

Wassink says they did further study to narrow down the gene mutation. Wassink says, "At some point in the embryonic development of the father, an abnormality occurred or a mutation arose in his primordial sperm cell." Wassink says the discovery of the mutation led to more research. He says the screened the gene, called "neurexin one," for mutations in about 400 other individuals with autism, but didn't find any additional mutations of the gene in people with autism. Wassink says it appears the mutations in the gene in this particular family are not a very common cause of autism.

Wassink says the exciting thing is that this is one of a groups of genes where mutations have been found in the proteins in the synapse that send messages between nerve cells. Wassink says this tells researchers that other genes and proteins in this particular synapse are worth looking at to screen for other mutations that might be related to autism.

Wassink says having a clue about where to look for the problem is important. He says there are well over 10,000 genes in the brain, and finding the right ones to look at is not easy. Wassink says this finding helps them look at a more specific set of genes. Wassink says the finding could eventually help with treatments for autism.

Wassink says it may indicate different types of medications to try in treating autism. Wassink, who is an associate professor of psychiatry, says this study does not show any link to an earlier study that indicated that the chances for autism increased with the age of the father. Wassink says age is not a factor in this finding.

ADVANCED PATERNAL AGE AND SOMETIMES ADVANCED MATERNAL AGE SEEMS TO RAISE THE RISK OF ACUTE LYMPHOBLASTIC LEUKEMIAS

HIG1: Nature. 2007 Apr 12;446(7137):758-64. Links
Comment in:
Nature. 2007 Apr 12;446(7137):739-40.
Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui CH, Relling MV, Evans WE, Shurtleff SA, Downing JR.
Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer.


Multivariable analyses showed a positive association between high paternal age (> or =35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96--2.31) but no association with maternal age


1: Br J Cancer. 2002 Feb 1;86(3):356-61. Links
Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study.Murray L, McCarron P, Bailie K, Middleton R, Davey Smith G, Dempsey S, McCarthy A, Gavin A.
Northern Ireland Cancer Registry, Department of Epidemiology and Public Health, The Queens University, Belfast, Riddel Hall, Stranmillis Road, Belfast BT9 5EE, UK. l.murray@qub.ac.uk

In a historical cohort study of all singleton live births in Northern Ireland from 1971-86 (n=434,933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (> or =35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96--2.31) but no association with maternal age. High birth weight (> or =3500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18--2.33). Children of mothers with a previous miscarriage or increased gestation (> or =40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29--0.80, and 0.67; 95% CI=0.48--0.94). Children born into more crowded households (> or =1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35-0.91 and 0.58; 95% CI=0.21-1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood. Copyright 2002 The Cancer Research Campaign

PMID: 11875699 [PubMed - indexed for MEDLINE]




Cancer Causes Control. 2002 Feb;13(1):15-25. Links
Birth characteristics, maternal reproductive history, hormone use during pregnancy, and risk of childhood acute lymphocytic leukemia by immunophenotype (United States).Ou SX, Han D, Severson RK, Chen Z, Neglia JP, Reaman GH, Buckley JD, Robison LL.
Department of Pediatrics, University of Minnesota, Minneapolis, USA. Xiao-Ou.Shu@mcmail.vanderbilt.edu

OBJECTIVE: To investigate the associations of birth characteristics and maternal reproductive factors with risk of childhood acute lymphoblastic leukemia (ALL) by immunophenotypic subtypes. METHODS: Data collected from a case-control study including 1842 ALL cases (age < 15 years) and 1986 individually matched controls were analyzed. Exposure information was obtained through telephone interviews of parents. RESULTS: Factors associated with risk of ALL from all subgroups combined included high birth weight (OR = 1.4, 95% CI = 1.1-1.8), high birth order (OR = 2.0, 95% CI = 1.3-3.0 for fourth-born child compared to first-born child). young maternal age (<20 compared to 25-29, OR = 1.4, 95% CI = 1.1-1.9), advanced paternal age (>39 compared to 25-29, OR = 1.4, 95% CI = 1.0-1.9), induced abortion prior to the index pregnancy (OR = 1.2, 95% CI = 1.0-1.4), and oral contraceptive use during the index pregnancy (OR = 1.5, 95% CI = 1.0-2.2) with children under the age of 2 (OR = 5.1, 95% CI = 1.0-24.7) being the predominantly affected group. Risk of early pre-B-cell ALL increased with advanced paternal age (OR = 1.7, 95% CI = 1.1-2.7) and high birth order (OR = 2.0, 95% CI = 1.1-3.6), while risk of pre-B-cell ALL increased with both younger (OR = 3.4, 95% CI = 1.4-8.4) and advanced maternal age (OR = 2.6, 95% CI = 1.1-5.9). T-cell ALL was associated with high birth weight (OR = 2.4, 95% CI = 1.1-5.5) and history of induced abortion (OR = 2.4, 95% CI = 1.3-4.5). CONCLUSION: This study suggests that the association of ALL with birth characteristics and maternal reproductive factors varies with the immunophenotype of the ALL. Future studies are needed to better understand the effect of maternal hormone in the development of subtype of childhood ALL.

PMID: 11899114 [PubMed - indexed for MEDLINE]



1: Int J Epidemiol. 2006 Dec;35(6):1495-503. Epub 2006 Sep 28. Links
Parental age and risk of childhood cancers: a population-based cohort study from Sweden.Yip BH, Pawitan Y, Czene K.
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 171 77 Stockholm, Sweden.

BACKGROUND: Frequent germ line cells mutations were previously demonstrated to be associated with aging. This suggests a higher incidence of childhood cancer among children of older parents. A population-based cohort study of parental ages and other prenatal risk factors for five main childhood cancers was performed with the use of a linkage between several national-based registries. METHODS: In total, about 4.3 million children with their parents, born between 1961 and 2000, were included in the study. Multivariate Poisson regression was used to obtain the incidence rate ratios (IRR) and 95% confidence interval (CI). Children <5 years of age and children 5-14 years of age were analysed independently. RESULTS: There was no significant result for children 5-14 years of age. For children <5 years of age, maternal age were associated with elevated risk of retinoblastoma (oldest age group's IRR = 2.39, 95%CI = 1.17-4.85) and leukaemia (oldest age group's IRR = 1.44, 95%CI = 1.01-2.05). Paternal age was significantly associated with leukaemia (oldest age group's IRR = 1.31, 95%CI = 1.04-1.66). For central nervous system cancer, the effect of paternal age was found to be significant (oldest age group's IRR = 1.69, 95%CI = 1.21-2.35) when maternal age was included in the analysis. CONCLUSION: Our findings indicate that advanced parental age might be associated with an increased risk of early childhood cancers.

THE MUTATION OCCURRED IN SPERM CELLS OF A FATHER WHO DOES NOT HAVE AUTISM BOTH OF HIS DAUGHERS ARE AUTISTIC, THEY INHERITED A CHROMOSOME WITH MISSING

DNA
MY QUESTION WAS HOW DOES THE SCIENTIST KNOW THAT THIS MUTATION OCCURRED DURING THE FATHER'S GESTATION AND NOT LATER? HOW OLD WAS THE FATHER WHEN THE FIRST DAUGHTER WAS BORN? COULD THIS BE A PATERNAL AGE AND OR A TOXIC EXPOSURE THAT DAMAGED HIS SPERMATAGONIA?

Researchers Learn More About Genetic Mutation Linked To Autism


By the Press-Citizen


From the University of Iowa Health News Service
University of Iowa researchers have learned more about a genetic mutation that contributes to autism. The mutation occurred in sperm cells of a father, who does not have autism, but passed the condition on to two of his children.

The investigators now know more about how the mutation causes problems with a specific gene and are testing for additional mutations of the same gene in other people with autism. Dr. Thomas Wassink, associate professor of psychiatry in UI’s Carver Col-lege of Medicine, is presenting the findings today at the annual International Meeting for Autism Research in Seattle.

Earlier this year, UI researchers and collaborators were part of an international team that identified, among other findings, de-letions in a gene called neurexin 1, which caused the two cases of autism in one family. The UI researchers and collaborators in-cluded Wassink; Dr. Val Sheffield, UI professor of pediatrics and a Howard Hughes Medical Investigator; Kacie Meyer, a graduate student in Wassink’s laboratory; and former UI investigator Dr. Joseph Piven, now professor of psychiatry at the University of North Carolina and director of the UNC Neurodevelopmental Disorders Research Center.

"Genes with the most compelling evidence of causing autism appear to be components of a specific kind of neuronal connec-tion, or synapse, called the glutamate synapse. The gene neurexin 1 was the fourth of these genes to be identified, and it is a scien-tifically interesting mutation because it wasn’t found in either of the parents, who do not have autism," Wassink said.

Instead, the mutation is a germline mosaic — meaning the deletion occurred only in the father’s sperm cells when he himself was in gestation. As result, the father did not have autism, but his two children, both daughters, inherited from him a chromosome that was missing a small piece of DNA that contained neurexin 1. The daughters now have autism.

Because of this missing DNA, certain proteins cannot form that normally contribute to glutamate synapses and, by extension, normal development.

"Now, using this information, we can look in a very detailed way at this gene in other families and begin to understand what happens when this protein that is normally active in the brain is missing," Wassink said.

Knowing more about how the deletions function could eventually lead to the development of diagnostic and therapeutic tools for autism, a complex brain disorder that inhibits a person’s ability to communicate and develop social relationships and is often accompanied by extreme behavioral challenges. Autism spectrum disorders are diagnosed in one in 166 children in the United States, affecting four times as many boys as girls., .

The Father's Age a Potent Risk Factor for Autism

17, February 2007 On the EBD Blog

The average age of fatherhood is increasing in the US and in Western Europe. Some research shows that offspring of older fathers are at increased risk for diseases and conditions (Bray et al., 2006). Some experts predict an upswing in cases of schizophrenia will accompany the increasing average paternal age. “The actual percentage of cases with paternal germ line-derived schizophrenia in a given population will depend on the demographics of paternal childbearing age, among other factors. With an upswing in paternal age, these cases would be expected to become more prevalent” (Malaspina et al., 2006). Approximately 25-33% of all cases of schizophrenia may be due to the father’s age at conception, according to Malaspina (2006). Malaspina sees a connection between advancing paternal age and neural functioning difficulties in people with autism and with schizophrenia. According to Tarin et al. (1998), there are well over 30 known conditions that the offspring of older fathers are more at risk for (see chart on paternal aging in the linked article).

The diagnosis of autism is increasing in the US and elsewhere (Centers for Disease Control, 2006). In a population study of 1990 through 1999, a total of 669,995 children, Atladóttir and colleagues (2007) reported increased diagnosese of autism, Torrette Syndrome, and hyperkinetic disorder. Is there a connection between increased cases of disorders such as autism and increased average paternal age? Psychiatrist Michael Craig Miller (2006), editor of the Harvard Mental Health Letter is convinced there is. Although a connection between the two would be corelational (not causal), the relationship encourages examination of the possibility that something related to paternal age (e.g. mutations in gametes) may contribute to the occurrence of autism. If there is a potential causal relationship, the new study by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network would provide a valuable opportunity to test the hypothesis.

Observations of a connection between advanced paternal age and difficulties for offspring go way back. Earlier research looking for a link between maternal age and autism also found the average paternal age (34) was much higher than the average age in the general population (Gillberg, 1980). Geneticist James F. Crow (1997) cites Wilhelm Weinberg (1862-1937) as noticing, during his 42 years of medical practice and helping 3,500 births, that the mutation rate might be a function of paternal age. Crow said, the evidence suggested that the greatest mutational health hazard in the population is fertile old men.

A study by Reichenberg et al. (2006) found a strong connection between cases of autism and advancing paternal age. Reichenberg and colleagues, who found more autism as paternal age increased, also found that the ratio of girls to boys in this cohort was 1:1, suggesting that this was a special subset of autism, maybe de novo rather than familial autism.

What might be the mechanism that produces higher rates of disorders among children of older fathers? The DNA in a 20 year-old male has been copied approximately100 times but in a 50 year-old father it has been copied over 800 times. Singh and colleagues (2003) studied differences in the sperm of older and younger men. Men over age 35 have sperm with lower motility and more highly damaged DNA in the form of double-strand breaks. The older group also had fewer apoptotic cells, an important discovery. (Apoptosis is form of cell death that protects the parent organism from problems or that permits differentiation, as in resorption of a tadpole’s tail.) A really key factor that differentiates sperm from other cells in the body is that they do not repair their DNA damage, as most other cells do. As a result, the only way to avoid passing DNA damage to a child is for the damaged cells to undergo apoptosis, a process that the study indicates declines with age. Singh is quoted in Science Blog (Sullivan, 2002) as explaining that, “In older men, the sperm are accumulating more damage, and those severely damaged sperm are not being eliminated.”

For links to most sources please go to the EBD blog
Sources

The following list of sources is for works cited in this document or for other studies finding a connection between age of fathers at conception and various disorders. Access to some of the Web-based resources may be limited because of the policies of the publishers.

Atladóttir, H. O., Parner, E. T., Schendel, D., Dalsgaard, S., Thomsen, P. H., & Thorsen, P. (2007). Time trends in reported diagnoses of childhood neuropsychiatric disorders. Arch Pediatr Adolesc Med., 161, 193-198. Link

Brown et al. (2002): Paternal age and risk of schizophrenia in adult offspring. Am J Psychiatry, 159, 1528-1533. Link

Bray, I., Gunnell, D., & Smith, G. D. (2006). Advanced paternal age: How old is too old? Journal of Epidemiology and Community Health, 60, 851-853. Link

Burd et al., (1999). Prenatal and perinatal risk factors for autism. J. Perinatal. Med., 27, 441-450. Link

Byrne, M., Agerbo, E., Ewald, H., Easton, W. W., & Mortensen, P. D. (2003). Parental age and risk of schizophrenia, A case control study. Arch Gen Psychiatry, 60, 673-678. Link

Centers for Disease Control, (2006). How common are Autism Spectrum Disorders (ASD)? Link

Centers for Disease Control. (2002). Prevalence of the Autism Spectrum Disorders (ASDs) in multiple areas of the United States, 2000 and 2002. Atlanta, GA: Author. Link

Crow, J. F. (1997). The high spontaneous mutation rate: Is it a health risk? Proc. Natl. Acad. Sci. USA, 94, 8380-8386. Link

Dalman, C., & Allebeck, D. (2002). Paternal age and schizophrenia: Further support for an association. Am J Psychiatry, 159, 1591-1592. Link

Gillberg, C. (1980). Maternal age and infantile autism. J. Autism and Developmental Disorders, 10, 293-297. Link

Lauritsen M. B., Pedersen, C. B., & Mortensen, P. B. (2005) Effect of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. J. Child Psychology and Psychiatry, 46, 963-971. Link

Miller, M. C. (2006) A new key to Autism. Aetna IntelliHealth, September 25. Link

Malaspina, D., et al. (2001): Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry, 58, 361-367. Link

Malaspina, D. (2006). In session with Dolores Malaspina, MD, MSPH: Impact of childhood trauma on psychiatric illness (interview by N. Sussman). Primary Psychiatry, 13(7), 33-36. Link

Malaspina, D. (2006). Schizophrenia risk and the paternal germ line. Schizophrenia Research Forum. Link

Rasmussen, F. (2006) Paternal age, size at birth, size in young adulthood&mdashrisk factors for schizophrenia. Eur Journal of Endocrinology, 155 Suppl 1:S65-69. Link

Reichenburg, A., Gross, R., Weiser, M. Bresnahan, M., Silverman, J. Harlap, S., et al. (2006). Advancing paternal age and autism. Arch Gen Psychiatry, 63, 1026-1032. Link

Singh, N. P., Muller, C. H., & Burger, R. E. (2003). Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertility and Sterility, 80, 1420-1430. Link

Sipos, A., Rasmussen, R., Harrison, G., Tynelius, P., Lews, G., Leon, D. A., et al. (2004). Paternal age and schizophrenia: A population based cohort study. BMJ, 329, 1070. Link

Sullivan, B. J. (2002). Research reveals a cellular basis for a male biological clock. Science Blog, 2002-11-25 22:31. Link

Tarin, J. J., Brines, J., & Cano, A. (1998). Long-term effects of delayed parenthood. Human Reproduction, 13, 2371-2376. Link

Tsuchiya, K. J., Takagai, S., Kawai, M., Matsumoto, H., Nakamura, K., Minabe, Y., et al. (2005). Advanced paternal age associated with an elevated risk for schizophrenia in offspring in a Japanese population. Schizophrenia Research, 76, 337-342. Link

Wohl, M. & Gorwood, P. (2006). Paternal ages below or above 35 are associated with a different risk for schizophrenia in offspring. Eur. Psychiatry, Dec 1 [Epub ahead of print]. Link

Zammit, S., Allebeck, P., Dalman, C., Lundgerg, I., Hemming, T., Owen, M. J., et al. (2003). Paternal age and risk for schizophrenia. Br. J. Psychiatry, 183, 405-408. Link

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[…] may view the document, including references and links to many resources on this topic, by following this link or by clicking on the page in the side rail (look under the heading […]

Pingback by EBDblog » Paternal age–more — 21 February 2007 @ 3:08 pm

http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5601a1.htm

February 9, 2007 / 56(SS01);1-11

Prevalence of Autism Spectrum Disorders — Autism and Developmental Disabilities Monitoring Network, Six Sites, United States, 2000

Corresponding author: Catherine Rice, PhD, Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, CDC, 1600 Clifton Road, N.E., MS E-86, Atlanta, GA 30333. Telephone: 404-498-3860; Fax: 404-498-3550; E-mail: crice@cdc.gov.

http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5601a1.htm

Comment by Leslie Feldman — 21 February 2007 @ 7:36 pm

Dr. Narendra P.Singh suggested that I elaborate about what happens when the DNA in the primitive sperm making cells divides hundreds and hundreds of times as men age.

I will try.

Mutations arise with each cell division and the mutation rate increases with age. There are base substitutions and deletions and other copying errors. In a man of 45 there have been 770 cell divisions ancestral to a sperm. See James F. Crow’s paper, “The high spontaneous mutation rate: Is it a health risk? in the sources section of the paper.

MISSISSIPPI DOING A VITALLY IMPORTANT STUDY FOR THE WHOLE NATION

Advanced Grandparental Age as a Risk Factor for Autism
This study is currently recruiting patients.
Verified by University of Mississippi Medical Center April 2007

Sponsored by: University of Mississippi Medical Center
Information provided by: University of Mississippi Medical Center
ClinicalTrials.gov Identifier: NCT00464477


Purpose



The Division of Medical Genetics at the University of Mississippi Medical Center is recruiting parents of children with a pervasive developmental disorder (including autism, autistic spectrum disorder, PDD-NOS, Asperger syndrome, childhood disintegrative disorder, and Rett syndrome) to participate in a study to help determine potential causes of the increasing prevalence of these disorders. The study is being conducted using an anonymous on-line survey available to parents through a secure link.

The study consists of approximately 90 questions about the affected child, siblings, parents, and grandparents, which will take roughly 10-15 minutes to complete. Several families will also be invited to participate in a phone interview. Both the survey and the phone interview are conducted using a self-designated code to protect anonymity and patient privacy. No identifying information such as name, date of birth, address, or phone number will be asked. Only questions regarding the year of birth of family members will be asked.

Condition
Autistic Disorder
Pervasive Developmental Disorder
Asperger Syndrome
Childhood Disintegrative Disorder
Rett Syndrome


MedlinePlus related topics: Asperger's Syndrome; Autism; Mental Health; Rett Syndrome
Genetics Home Reference related topics: Rett syndrome

Study Type: Observational
Study Design: Natural History, Cross-Sectional, Random Sample, Retrospective Study

Official Title: Advanced Grandparental Age as a Risk Factor for Autism and Other Pervasive Developmental Disorders

Further study details as provided by University of Mississippi Medical Center:
Study start: March 2007; Expected completion: May 2007


Autism is a genetically heterogeneous entity. Although numerous studies have demonstrated a strong genetic basis, no clear etiology has been identified to date. Recently, two studies have demonstrated an increased risk of autism in children born to fathers over the age of 40. However, given the large male-to-female predominance of autism, it is likely that new mutations on the X chromosome account for a significant number of affected cases. Due to the maternal origin of the X chromosome in males, we hypothesize that advanced maternal-grandpaternal age may also be a risk factor for autism. Precedence for this theory exists with other X-linked disorders such as Duchenne muscular dystrophy and Rett syndrome. Additionally, it has been demonstrated that maternal psychiatric illness, but not paternal psychiatric illness, is more prevalent among parents of children with autism. Using anonymous surveys of families with autistic children, we seek to identify the ages of grandparents at the time the parents were born in order to determine if advanced maternal-grandpaternal age is associated with an increased risk for autism when adjusted for advanced maternal and paternal age. Additionally, we will seek out sister-pairs in order to identify any statistical significance between the ages of the maternal grandfather at delivery of each sister. If advanced maternal-grandpaternal age is, in fact, a risk factor, it would help direct molecular researchers towards genes on the X chromosome as potential etiologies for autism. Also, further study of potential mutagenic exposures in the environment of grandparents may help elucidate the reason for the increasing incidence of autism in recent decades.
Eligibility

Genders Eligible for Study: Both
Criteria
Inclusion Criteria:

Individuals of any age with autism, autistic disorder, autistic spectrum disorder, Asperger syndrome, pervasive developmental disorder, PDD-NOS, Rett syndrome, or Childhood disintegrative disorder
Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00464477

Omar Abdul-Rahman, MD 601-984-1900 OAbdulrahman@prevmed.umsmed.edu


United States, Mississippi
University of Mississippi Medical Center, Jackson, Mississippi, 39216, United States; Recruiting
Omar Abdul-Rahman, MD 601-984-1900 OAbdulrahman@prevmed.umsmed.edu



Study chairs or principal investigators

Omar Abdul-Rahman, MD, Principal Investigator, University of Mississippi Medical Center