Is there a paternal age effect for aneuploidy?

Cytogenet Genome Res. 2011;133(2-4):280-91. Epub 2011 Jan 6.

Is there a paternal age effect for aneuploidy?

Fonseka KG, Griffin DK.


Source

School of Biosciences, University of Kent, Canterbury, UK.


Abstract

Finding a positive association between paternal age and the incidence of aneuploidy is not difficult. A cursory analysis however reveals that any association is indirect, brought about by a close correlation between paternal age and maternal age. Approaches for dissecting out the confounding age effects of the mother has led to a lively exchange among epidemiologists, with perhaps a consensus for the absence of a paternal age effect, at least for trisomy 21. Molecular studies revealed the relatively minor contribution of paternal errors to trisomy, but even research on the paternally derived trisomies alone has been inconclusive; thus studies focussed directly on the sperm heads. Human-hamster fusion assays were superseded by FISH for establishing any possible link between age and the proportion of disomic sperm in an ejaculate. Despite innumerable microscope hours however, although convincing studies suggesting an age effect for disomies 1, 9, 18 and 21 and the sex chromosomes are in the literature, others failed to notice any association for these or other chromosomes. It is biologically plausible that chromosomal non-disjunction errors should increase with age. Male reproductive hormone production, testicular morphology and semen parameters all decline slowly with age and paternal age is implicated in congenital birth defects, such as achondroplasia and Apert syndromes and also linked to compromised DNA repair mechanisms. Despite several decades of epidemiological and molecular cytogenetic studies, however, we are still not close to a definitive answer of whether or not there is a paternal age effect for aneuploidy. In this review we conclude by questioning the efficacy of FISH because of difficulties in detecting nullisomy and because of evidence that the centromeres (from which most sperm-FISH probes are derived) cluster at the nuclear centre. Array-based approaches may well supersede FISH in addressing the question of a paternal age effect; for now, however, the jury is still out.

Copyright © 2011 S. Karger AG, Basel.

Parental Age and Autism Spectrum Disorders

Parental Age and Autism Spectrum Disorders

The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing.

The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing. In Canada, 11 per cent of first births now occur in women aged 35 and older, up from five per cent in 1987.

Photograph by: Thinkstock, canada.com


Men, and not just women, need to be aware of the "reproductive consequences" of postponing parenthood, new national guidelines on the risks of delayed child-bearing warn.


Though women especially should recognize that their "fecundity and fertility" starts to decline precipitously after 32, a man's semen quality and fertility also worsens with age, according to guidelines endorsed by the Society of Obstetricians and Gynaecologists of Canada.


In addition, babies born to fathers of "advanced paternal age" — defined as 40 and older at the time of conception — are at increased risk of genetic disorders, as well as schizophrenia, autism and some forms of cancer, according to the authors.


The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing. In Canada, 11 per cent of first births now occur in women aged 35 and older, up from five per cent in 1987.


If the trend holds, society can expect to spend more on intensive care, special care nurseries and community services for children born to older parents who may have developmental, hearing, speech or language problems, the authors say.


Read more: http://www.canada.com/health/Postponing+parenthood+could+have+serious+consequences+warns+study/6007363/story.html#ixzz1jjrwcZMI

Mol Autism. 2010 Feb 22;1(1):2. Paternal age increases the risk for autism in an Iranian population sample.

Mol Autism. 2010 Feb 22;1(1):2.
Paternal age increases the risk for autism in an Iranian population sample.
Sasanfar R, Haddad SA, Tolouei A, Ghadami M, Yu D, Santangelo SL.
SourceDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA. ssantangelo@pngu.mgh.harvard.edu.

Abstract
BACKGROUND: Autism is a neurodevelopmental disorder which is known to have a strong genetic component and is most likely oligogenic. However, the necessary role of environmental factors has been well documented. Prior research suggests that parental characteristics, such as age and level of education, may be associated with a risk of autism. Parental age has been shown to be associated with many disorders, such as schizophrenia, childhood cancer and fetal death. However, results from studies of parental age and autism are inconsistent.

METHODS: In the present study, we investigated the association of autism with parental age in 179 autism cases and 1611 matched cohort children from Iran. Each case was matched with nine cohort controls on parental education, sex, order of birth, consanguineous marriage, urbanism and province of residence. The Cox regression model was used to carry out conditional logistic regression on the matched data.

RESULTS: There was a significant association between higher paternal age, but not maternal age, and an increasing risk of autism. An analysis of the combined effect of parental age and education also revealed that parents with higher education had an increased risk of having autistic children, with a dose-response effect of parental age.

CONCLUSIONS: This study, which is the first epidemiological study of autism in Iran, provides evidence of the association of paternal age and risk of autism.

PMID: 20678245 [PubMed] PMCID: PMC2907564Free PMC Article

Maternal and Paternal Age are Jointly Associated with Childhood Autism in Jamaica.

Autism Dev Disord. 2012 Jan 10. [Epub ahead of print]
Maternal and Paternal Age are Jointly Associated with Childhood Autism in Jamaica.
Rahbar MH, Samms-Vaughan M, Loveland KA, Pearson DA, Bressler J, Chen Z, Ardjomand-Hessabi M, Shakespeare-Pellington S, Grove ML, Beecher C, Bloom K, Boerwinkle E.
SourceDivision of Epidemiology, Human Genetics, and Environmental Sciences (EHGES), School of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, 77030, USA, Mohammad.H.Rahbar@uth.tmc.edu.

Abstract
Several studies have reported maternal and paternal age as risk factors for having a child with Autism Spectrum Disorder (ASD), yet the results remain inconsistent. We used data for 68 age- and sex-matched case-control pairs collected from Jamaica. Using Multivariate General Linear Models (MGLM) and controlling for parity, gestational age, and parental education, we found a significant (p < 0.0001) joint effect of parental ages on having children with ASD indicating an adjusted mean paternal age difference between cases and controls of [5.9 years; 95% CI (2.6, 9.1)] and a difference for maternal age of [6.5 years; 95% CI (4.0, 8.9)]. To avoid multicollinearity in logistic regression, we recommend joint modeling of parental ages as a vector of outcome variables using MGLM.

PMID: 22230961 [PubMed - as supplied by publisher]