GWAS on birth year infant mortality rates provides evidence of recent natural selection

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 examin...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 119; no. 12; p. e2117312119
Main Authors Wu, Yuchang, Furuya, Shiro, Wang, Zihang, Nobles, Jenna E, Fletcher, Jason M, Lu, Qiongshi
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 22.03.2022
Subjects
Biological Sciences
Birth
Cognition
Exposure
Fertility
Genetic diversity
Genetic variance
Genome-wide association studies
Genome-Wide Association Study
Genomes
Humans
Infant Mortality
Infant, Newborn
Infants
Natural selection
Polymorphism, Single Nucleotide
Populations
Selection, Genetic
Social Sciences
United Kingdom > UK
recent natural selection
infant mortality
regional GWAS
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Summary: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.
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Author contributions: J.E.N., J.M.F., and Q.L. designed research; Y.W. performed research; Y.W., S.F., and Z.W. analyzed data; and Y.W., S.F., J.E.N., J.M.F., and Q.L. wrote the paper.
Edited by Dalton Conley, Princeton University, Princeton, NJ; received September 20, 2021; accepted February 7, 2022
1J.M.F. and Q.L. contributed equally to this work.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2117312119