Paternal age effect in psychosis mediated by mother’s genetic risk
MedWire News: The link between advanced paternal age (APA) and risk for non-affective psychosis (NAP) in offspring appears to be explained by genetic load in the mother, show results of a large Finnish cohort study.
The findings argue against the prevailing theory that accumulated de novo mutations in the paternal germline explain the APA-NAP link.
"Older fathers may be more likely to mate with women who have increased schizophrenia liability in the form of schizotypal (or other cluster A) personality traits, which would be more common than maternal schizophrenia," explain Brian Miller (Georgia Health Sciences University, Augusta, USA) and colleagues in the journal Schizophrenia Research.
In a previous study Miller et al found a significant linear increased risk for NAP in the offspring of older fathers, with no obvious cut-off point beyond which paternal age should be considered "advanced."
One hypothesis for these findings is elevated de novo mutations in the paternal germ line, while the possibility of epigenetic changes, such as imprinting or DNA methylation, has been proposed but not investigated.
Another hypothesis is that the association between APA and NAP may be due to delayed childbearing by fathers with increased liability for schizophrenia (eg, schizotypal or other cluster A personality traits).
APA may also be associated with an adverse psychosocial environment for offspring, thereby increasing schizophrenia risk, for example, through unwanted pregnancy and paternal death during childhood.
"The association between APA and family history of schizophrenia, which could provide insights into the mechanism of the 'APA effect,' has not been adequately explored," comment Miller et al.
They therefore examined the Finnish NAP Cohort, which includes all individuals with NAP born in Finland between 1950 and 1969 (n=13,712), and the Northern Finland 1966 Birth Cohort (NFBC), a general population birth cohort (n=10,224).
Binary logistic regression analysis revealed that having a mother with schizophrenia was significantly associated with APA in the Finnish NAP Cohort (odds ratio [OR] for linear trend=1.20) and in the NFBC 1966 sample (OR=1.14).
By contrast, there was no association between having a father with schizophrenia and APA.
Discussing the findings, the researchers note that in addition to increased genetic risk from the mother, assortative mating may contribute to the observed association between APA and maternal schizophrenia.
"Assortative mating, the tendency for mated pairs to be more similar for a given phenotypic trait than expected if mating occurred at random, has been shown for a variety of psychiatric conditions, including schizophrenia," they comment.
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By Andrew Czyzewski