Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706.
Center for Demography of Health and Aging, University of Wisconsin-Madison, Madison, WI 53706.
Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2117312119. doi: 10.1073/pnas.2117312119. Epub 2022 Mar 14.
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.
在对自然选择过程进行了一个多世纪的表型测量之后，最近的许多工作都在探讨分子遗传测量与下一代实际适应度之间的关系。我们通过研究随着死亡率暴露的增加哪些遗传变异在人群中“持续存在”，从而对当代选择压力进行了创新性的研究。具体来说，我们采用了一种所谓的“区域 GWAS”（全基因组关联研究），将英国各地区和年份的婴儿死亡率（IMR）与英国生物银行中出生队列的常见遗传变异联系起来。这些队列（出生于 1936 年至 1970 年之间）的 IMR 从每千例活产 65 例以上下降到 20 例以下，与战时暴露相关的死亡率有很大的国家内部差异和波动。我们的研究结果显示了几个全基因组显著的基因座，包括 LCT 和 TLR10/1/6，这些基因座与妊娠期和婴儿期的区域队列 IMR 暴露有关。在包括生育能力、认知、健康行为和健康结果在内的多个领域都发现了遗传相关性，这表明在现代人群中，队列选择起着重要作用。
