Distinct genetic architecture in the tails of complex traits

Data processing UKB genotype data The UKB is a prospective cohort study of approximately 500,000 participants recruited across the United Kingdom from 2006 to 2010 (ref. 18 ). Phenotype data of anthropometric, biological and lifestyle measures were collected at baseline and in follow-up surveys, with further linkage to health and disease record data. The genetic dataset consists of 488,377 samples genotyped at 805,426 SNPs. To define population ancestries, 4-means clustering analysis was conducted on the first two principal components of the genotype data. Ancestries were then defined according to the country of birth (field ID: 20115) of the majority of individuals in the cluster, resulting in 461,931 European, 11,074 South Asian, 7,935 African, 2,585 West Asian and 2,550 East Asian individuals, and 1,619 individuals in clusters for which there was no majority country of birth. Subsequent to clustering, standard QC procedures were applied independently to each ancestry cluster. SNPs with a minor allele frequency (MAF) 0.02 or Hardy–Weinberg equilibrium test P 0.044) 41 . After these QC steps, 411,948 unrelated individuals remained, of whom 387,472 were of European ancestry. The European ancestry cluster included 18,340 individuals with repeated measures that were set aside, as well as 24,476 individuals of multiple non-European ancestries for replication analyses. This resulted in up to 369,132 unrelated individuals of European ancestry for the primary POPout analyses. …