RT Journal Article
SR Electronic
T1 Mega-analysis of 31,396 individuals from 6 countries uncovers strong gene-environment interaction for human fertility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 049163
DO 10.1101/049163
A1 Felix C. Tropf
A1 Renske M. Verweij
A1 Peter J. van der Most
A1 Gert Stulp
A1 Andrew Bakshi
A1 Daniel A. Briley
A1 Matthew Robinson
A1 Anastasia Numan
A1 Tõnu Esko
A1 Andres Metspalu
A1 Sarah E. Medland
A1 Nicholas G. Martin
A1 Harold Snieder
A1 S. Hong Lee
A1 Melinda C. Mills
YR 2016
UL http://biorxiv.org/content/early/2016/05/02/049163.abstract
AB 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.Authors Summary Fertility 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.