Abstract
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 between 1936 and 1970) 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 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.