Daniel A Briley | Search bioRxiv

bioRxiv2016

Genetic Influences on Hormonal Markers of Chronic HPA Function in Human Hair

Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the human biological stress response, with wide-ranging effects on physiological function and psychiatric health. In both humans and animals, cortisol is frequently studied as a biomarker for exposure to environmental stress. Relatively little attention has been paid to the possible role of genetic variation in heterogeneity in chronic cortisol, in spite of well-studied biological pathways of glucocorticoid function. Using recently developed technology, hair samples can now be used to measure accumulation of cortisol over several months. In contrast to more conventional salivary measures, hair cortisol is not influenced by diurnal variation or transient hormonal reactivity. In an ethnically and socioeconomically diverse sample of 1 070 child and adolescent twins and multiples from 556 unique families, we estimated genetic and environmental influences on hair concentrations of cortisol and its inactive metabolite, cortisone. We identified sizable genetic influences on cortisol that decrease with age, concomitant with genetic influences on cortisone that increase with age. Shared environmental influences on cortisol and cortisone were modest and, for cortisol, decreased with age. Twin-specific, non-shared environmental contributions to cortisol and cortisone became increasingly correlated with age. We find some evidence for sex differences in the biometric contributions to cortisol, but no strong evidence for main or moderating effects of family socioeconomic status on cortisol or cortisone. This study constitutes the first genetic study of hormone concentrations in human hair, and provides the most definitive characterization to-date of age and socioeconomic influences on hair cortisol.

Genetics↗

bioRxiv2016

Mega-analysis of 31,396 individuals from 6 countries uncovers strong gene-environment interaction for human fertility

Family and twin studies suggest that up to 50% of individual differences in human fertility within a population might be heritable. However, it remains unclear whether the genes associated with fertility outcomes such as number of children ever born (NEB) or age at first birth (AFB) are the same across geographical and historical environments. By not taking this into account, previous genetic studies implicitly assumed that the genetic effects are constant across time and space. We conduct a mega-analysis applying whole genome methods on 31,396 unrelated men and women from six Western countries. Across all individuals and environments, common single-nucleotide polymorphisms (SNPs) explained only ~4% of the variance in NEB and AFB. We then extend these models to test whether genetic effects are shared across different environments or unique to them. For individuals belonging to the same population and demographic cohort (born before or after the 20th century fertility decline), SNP-based heritability was almost five times higher at 22% for NEB and 19% for AFB. We also found no evidence suggesting that genetic effects on fertility are shared across time and space. Our findings imply that the environment strongly modifies genetic effects on the tempo and quantum of fertility, that currently ongoing natural selection is heterogeneous across environments, and that gene-environment interactions may partly account for missing heritability in fertility. Future research needs to combine efforts from genetic research and from the social sciences to better understand human fertility.\n\nAuthors SummaryFertility behavior - such as age at first birth and number of children - varies strongly across historical time and geographical space. Yet, family and twin studies, which suggest that up to 50% of individual differences in fertility are heritable, implicitly assume that the genes important for fertility are the same across both time and space. Using molecular genetic data (SNPs) from over 30,000 unrelated individuals from six different countries, we show that different genes influence fertility in different time periods and different countries, and that the genetic effects consistently related to fertility are presumably small. The fact that genetic effects on fertility appear not to be universal could have tremendous implications for research in the area of reproductive medicine, social science and evolutionary biology alike.

Genetics↗