Association Of Paternal Age Research Articles

Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies

Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged ≥50 years were 2.2 times (95% confidence interval: 1.26-3.88: P=0.006) more likely to have autism than offspring of men aged ≤29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.

Case–control analysis of paternal age and trisomic anomalies

ObjectivesTo determine whether older paternal age increases the risk of fathering a pregnancy with Patau (trisomy 13), Edwards (trisomy 18), Klinefelter (XXY) or XYY syndrome.DesignCase–control: cases with each of these...

Paternal age increases the risk for autism in an Iranian population sample

BackgroundAutism 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.MethodsIn 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.ResultsThere 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.ConclusionsThis study, which is the first epidemiological study of autism in Iran, provides evidence of the association of paternal age and risk of autism.

Association of Paternal Age and Risk for Major Congenital Anomalies From the National Birth Defects Prevention Study, 1997 to 2004

The objective of this study was to examine the associations between paternal age and birth defects of unknown etiologies while carefully controlling for maternal age. By using 1997 to 2004 data from the National Birth Defects Prevention Study, we fit logistic regression models with paternal and maternal age as continuous variables while adjusting for demographic and other factors. Elevated odds ratios (ORs) for each year increase in paternal age were found for cleft palate (OR. 1.02, 95% confidence interval [95% CI], 1.00-1.04), diaphragmatic hernia (OR, 1.04; 95% CI, 1.02-1.06), right ventricular outflow tract obstruction (OR, 1.03; 95% CI, 1.01-1.04), and pulmonary valve stenosis (OR, 1.02, 95% CI, 1.01-1.04). At younger paternal ages, each year increase in paternal age correlated with increased odds of having offspring with encephalocele, cataract, esophageal atresia, anomalous pulmonary venous return, and coarctation of the aorta, but these increased odds were not observed at older paternal ages. The effect of paternal age was modified by maternal age for gastroschisis, omphalocele, spina bifida, all orofacial clefts, and septal heart defects. Our findings suggest that paternal age may be a risk factor for some multifactorial birth defects.

Association of Paternal Age and Risk for Major Congenital Anomalies From the National Birth Defects Prevention Study, 1997 to 2004

Association of Paternal Age and Risk for Major Congenital Anomalies From the National Birth Defects Prevention Study, 1997 to 2004

Paternal age and reproduction

Due to various sociological factors, couples in developed countries are increasingly delaying childbearing. Besides ethical, economical and sociological issues, this trend presents us with several complex problems in reproduction. Although it is well-known that maternal age has a negative effect on fertility and increases the risk of adverse outcome during pregnancy and in offspring, the paternal influence on these outcomes is less well researched and not well-known. We performed a systematic search of PubMed, and retrieved original articles and review articles to update our previous survey in this journal. This review highlights the link between male age and genetic abnormalities in the germ line and summarizes the knowledge about the effects of paternal age on reproductive function and outcome. Increasing paternal age can be associated with decreasing androgen levels, decreased sexual activity, alterations of testicular morphology and a deterioration of semen quality (volume, motility, morphology). Increased paternal age has an influence on DNA integrity of sperm, increases telomere length in spermatozoa and is suggested to have epigenetic effects. These changes may, at least in part, be responsible for the association of paternal age over 40 years with reduced fertility, an increase in pregnancy-associated complications and adverse outcome in the offspring. Although higher maternal age can be an indication for intensive prenatal diagnosis, including invasive diagnostics, consideration of the available evidence suggests that paternal age itself, however, provides no rationale for invasive procedures.

Investigation of factors associated with paternal nondisjunction of chromosome 21

Previous studies on relatively small samples of individuals with trisomy 21 caused by paternally derived errors have shown that: (1) advanced paternal age is not a risk factor for chromosome 21 nondisjunction (NDJ), (2) absence of recombination, but not the location of recombination is associated with paternal NDJ and (3) there is an excess of males among live-births with paternally derived trisomy 21. An excess of males is also observed among all individuals with trisomy 21. Using 128 families that had a child with trisomy 21 due to a paternally derived error, we examined: paternal age, recombination and the male/female sex ratio. We genotyped STRs along 21q to identify the origin of the error and the location of recombination on the paternal chromosome. Results showed that 32% of paternal meiotic errors occurred in meiosis I (MI) and 68% in meiosis II (MII). We confirmed the lack of a paternal age association with either type of error (mean paternal age for controls, MI, and MII errors: 31.3 +/- 6.6, 32.2 +/- 6.3, 30.6 +/- 6.5, respectively). However, contrary to previous findings, we did not find altered patterns of recombination among paternal MI or MII errors. We found an increased male/female sex ratio among paternal (1.28, 95% CI: 0.68-1.91) and maternal (1.16, 95% CI: 1.02-1.33) meiotic errors. While the sex ratio among individuals with paternal errors was not statistically significant, these findings suggest that selection against female fetuses with trisomy 21 may contribute to the excess of males observed among all individuals with trisomy 21.

Reply to Herlihy and Halliday

We thank the authors for their comments on our paper. They query as to why we do not mention paternal age as a possible explanation for the increase in prevalence of Klinefelters compared to XYY and XXX. We agree that it may be a partial explanation, but we do not believe that there is a substantial body of evidence of an association of paternal age with the birth of a child with Klinefelters. Of the five studies referenced in a recent meta-analysis, only one study found a significant positive association between paternal age and Klinefelters.1

ICOS controls the pool size of effector-memory and regulatory T cells

<h3>Abstract</h3> <b>Objective</b> To investigate the association of paternal age at conception with the risk of offspring developing schizophrenia. <b>Design</b> A population based cohort study. <b>Setting</b> Sweden. <b>Subjects</b> 754 330 people born in Sweden between 1973 and 1980 and still alive and resident in Sweden at age 16 years. <b>Main outcome measures</b> Hospital admission with schizophrenia or non-schizophrenic, non-affective psychosis. <b>Results</b> After adjustment for birth related exposures, socioeconomic factors, family history of psychosis, and early parental death the overall hazard ratio for each 10 year increase in paternal age was 1.47 (95% confidence interval 1.23 to 1.76) for schizophrenia and 1.12 (0.98 to 1.29) for non-schizophrenic non-affective psychosis. This association between paternal age and schizophrenia was present in those with no family history of the disorder (hazard ratio for each 10 year increase in paternal age 1.60, 1.32 to 1.92), but not in those with a family history (0.91, 0.44 to 1.89) (P = 0.04 for interaction). <b>Conclusions</b> Advancing paternal age is an important independent risk factor for schizophrenia. The stronger association between paternal age and schizophrenia in people without a family history provides further evidence that accumulation of de novo mutations in paternal sperm contributes to the overall risk of schizophrenia.

Parental age and risk of acute lymphocytic leukaemia and embryonal tumours in the Piedmont Region, Italy

Relative risks (RRs) for maternal and paternal ages were estimated using log-binomial regression adjusting for sex and year of birth. Paternal and maternal age effects were mutually adjusted. Out of a population of more than 630000 children followedup from birth to age five, we observed 229 cases of ALL and 284 cases of embryonal tumours. Older maternal age was associated with ALL risk, irrespective of adjustment for paternal age (Table 1). Conversely, an apparent association with paternal age disappeared when maternal age was included in the model. Both maternal and paternal ages were independently associated with the risk of embryonal tumours, although the RR estimates were attenuated when both variables were introduced in the model. Subgroup analyses were carried out for cancer types with at least 30 observed cases. The strongest association of paternal age was found with embryonal tumours of the kidney (maternal age-adjusted RR for each 5-year increase in paternal age: 1.29, 95% confidence intervals: 0.98–1.68). In our study, ALLs were analysed separately since they are the most frequent type of tumour among children aged less than five. Other types of tumours were grouped and analysed together, under the assumption that parental age might have a stronger effect on tumours with an embryonal origin. Maternal age was associated with both leukaemia and embryonal tumour risk, whereas paternal age, which could relate to accumulation of germ cell mutations, 4 was associated with embryonal tumours only. Conflict of interest. None declared.

Association of paternal age with prevalence of selected birth defects

Unlike maternal age, the effect of paternal age on birth defect prevalence has not been well examined. We used cases from the Texas birth defect registry, born during 1996-2002, to evaluate the association of paternal age with the prevalence of selected structural birth defects. Poisson regression was used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) associated with paternal age for each birth defect, adjusting for maternal age, race/ethnicity, and parity. Relative to fathers ages 25-29 years, fathers 20-24 years of age were more likely to have offspring with gastroschisis (PR 1.47, 95% CI: 1.12-1.94), and fathers 40+ years old were less likely to have offspring with trisomy 13 (PR 0.40, 95% CI: 0.16-0.96). No association was seen between paternal age and prevalence of anencephaly and encephalocele. A selection bias was observed for the other birth defects in which cases of younger fathers were more often excluded from study. In studies of birth defect risk and paternal age, the source of information may affect the validity of findings.

Association of paternal age at birth and the risk of breast cancer in offspring: a case control study

BackgroundOlder paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea.MethodsHistologically confirmed breast cancer cases (n = 1,011) and controls (n = 1,011) with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration.ResultsThe risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025). The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged <30 years. This association was profound in breast cancer cases in premenopausal women (OR = 1.9, 95% CI = 1.12–3.26, for paternal aged ≥40 vs. <30) (p for trend = 0.031). Although the risk of breast cancer increased as maternal age increased up to the intermediate, and then reduced; the risks in women whose mother were aged 25–29, 30–34, and ≥35 yrs at birth compared to women whose mothers were aged <25 years, were 1.2, 1.4, and 0.8, respectively, the trend was not significant (p for trend = 0.998).ConclusionThese findings suggest that older paternal age increases the risk of breast cancer in their female offspring.

Paternal age and intelligence: implications for age-related genomic changes in male germ cells

A robust association between advancing paternal age and schizophrenia risk is reported, and genetic changes in the germ cells of older men are presumed to underlie the effect. If that is so, then the pathway may include effects on cognition, as those with premorbid schizophrenia are reported to have lower intelligence. There are also substantial genetic influences on intelligence, so de novo genetic events in male germ cells, which accompany advancing paternal age, may plausibly influence offspring intelligence. An association of paternal age with IQ in healthy adolescents may illuminate the mechanisms that link it to schizophrenia. We examined the association of paternal age and IQ scores using the Israeli Army Board data on 44 175 individuals from a richly described birth cohort, along with maternal age and other potential modifiers. A significant inverted U-shaped relationship was observed between paternal age and IQ scores, which was independent from a similar association of IQ scores with maternal age. These relationships were not significantly attenuated by controlling for multiple possible confounding factors, including the other parent's age, parental education, social class, sex and birth order, birth weight and birth complications. Overall, parental age accounted for approximately 2% of the total variance in IQ scores, with later paternal age lowering non-verbal IQ scores more than verbal IQ scores. We found independent effects of maternal and paternal age on offspring IQ scores. The paternal age effect may be explained by de novo mutations or abnormal methylation of paternally imprinted genes, whereas maternal age may affect fetal neurodevelopment through age-related alterations in the in-utero environment. The influence of late paternal age to modify non-verbal IQ may be related to the pathways that increase the risk for schizophrenia in the offspring of older fathers.

Paternal age and schizophrenia: a population based cohort study

Objective To investigate the association of paternal age at conception with the risk of offspring developing schizophrenia.Design A population based cohort study.Setting Sweden.Subjects 754 330 people born in Sweden between...

Secular trend and associated factors of twinning in Taiwan.

Delivery records of public hospitals and local health centers were analyzed to investigate the secular trend of multiple births from 1955 to 1990 in Taiwan. Twinning rates decreased gradually from the late 1950s to 1973, slightly increased and remained stable from 1974 to 1980, and then increased strikingly from 1981 to 1990. During the study period, MZ rates were consistently higher than DZ rates except in 1986 when a higher DZ rate was observed. The highest MZ rate of 7.7 per 1,000 deliveries was observed in 1985, while the highest DZ rate of 4.6 per 1,000 deliveries was observed in 1986. The triplet incidence rate also declined from the early 1960s to 1973 and then increased markedly from 1974 to 1990. A case-control study including 482 MZ and 252 DZ twin pairs and 1,496 singletons was carried out in four teaching hospitals in Taipei City between October 1985 and June 1989 to examine factors related to twinning. The zygosity of twin pairs was determined by sex, placentation and red blood cell antigens. Multiple logistic regression analysis showed that the higher the maternal age, the lower the MZ and DZ rates, while the higher the parity, the higher the rates. There was no association of paternal age or of maternal educational level with twinning rates.