“GWAS on Birth Year Infant Mortality Rates Provides Evidence of Recent Natural Selection”, 2022-03-13 ():
Quantifying natural selection in human populations is a central topic in evolutionary biology and human genetics. Current studies to identify which single-nucleotide polymorphism has undergone selection suffer from limited sample sizes and large uncertainties in the timing of selection.
In this study, we advance the field by showing that a genome-wide association study (GWAS) on infant mortality rate can identify recent selection signals. Our study produces well-powered genome-wide maps for selection.
It replicates 2 selection signals that were detected in a previous study using ancient DNA, substantially improves the resolution on the timing of selection, and provides evidence for very recent selection during World War II. It also provides fundamental insights into how to interpret GWAS results.
Following more than a century of phenotypic measurement of natural selection processes, much recent work explores relationships between molecular genetic measurements and realized fitness in the next generation.
We take an innovative approach to the study of contemporary selective pressure by examining which genetic variants are “sustained” in populations as mortality exposure increases. Specifically, we deploy a so-called “regional GWAS” (genome-wide association study) that links the infant mortality rate (IMR) by place and year in the United Kingdom with common genetic variants among birth cohorts in the UK Biobank. These cohorts (born 1936–34197054ya) saw a decline in IMR from above 65 to under 20 deaths per 1,000 live births, with substantial subnational variations and spikes alongside wartime exposures.
Our results show several genome-wide statistically-significant loci, including LCT and TLR10/1/6, related to area-level cohort IMR exposure during gestation and infancy. Genetic correlations are found across multiple domains, including fertility, cognition, health behaviors, and health outcomes, suggesting an important role for cohort selection in modern populations.
…Genetic Correlation with 50 Complex Traits: We next examined genetic correlation (40) between birth year IMR and a set of 50 traits widely assessed as outcomes of selection processes (Figure 5 & Dataset S4).
Among known target traits of selection (10), we found a statistically-significant correlation with vitamin D but found null results on hair and skin color. Our results are consistent with other approaches showing correlations with genetics of fertility (age at first birth) but do not find effects for number of children ever born, age at menarche, or age at menopause. Recall that Sanjak et al 11 reported inconsistent findings between reproductive success and age at menarche (positive) and age at menopause (negative), which the authors label as “less explicable” than other results; as a comparison, we obtained null results for these 2 traits. Similar to earlier findings (6, 8), we show correlations with EA and cognition, but we extend this finding by showing these results are driven by the direct-EA component and not by the indirect-EA component mediated by family environment (ie. genetic nurture), using methods in Wu et al 41, suggesting that the selection pressure more directly applies to the child’s genetics on education rather than parental behavior that affects their children’s education. The difference in these findings suggest a broader need for caution when examining the genetic correlation findings, as we cannot decouple parental and child genetics in these results. We also find relationships with anthropometrics, like Sanjak et al 11, but substantially extend our domains of interest to show findings for cardiovascular disease, tobacco use, and a variety of mental health conditions. The null findings on birth weight are suggestive that studies linking birthweight to insults akin to those prevailing during the 1930s and 1940s in the United Kingdom are likely capturing the deleterious effects of the disease environment (and accompanying wartime conditions) during that time, versus the differential survival of pregnancies (42, 43).