Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases

TLDR

Clinical measurements can be viewed as useful intermediate phenotypes to promote understanding of complex human diseases. The study aimed to uncover the genetic basis of 58 quantitative traits in 162,255 Japanese individuals through a genome‑wide association study. We performed a GWAS on 58 quantitative traits in 162,255 Japanese participants. The analysis uncovered 1,407 trait‑associated loci, including 679 novel ones, and, by integrating 32 additional Japanese GWAS, revealed extensive pleiotropy, genetic correlations, and cell‑type specificity linking clinical measurements to complex diseases, thereby demonstrating that genetic signals from clinical traits can recapture disease relevance and illuminate unknown etiologies.

Abstract

Clinical measurements can be viewed as useful intermediate phenotypes to promote understanding of complex human diseases. To acquire comprehensive insights into the underlying genetics, here we conducted a genome-wide association study (GWAS) of 58 quantitative traits in 162,255 Japanese individuals. Overall, we identified 1,407 trait-associated loci (P < 5.0 × 10-8), 679 of which were novel. By incorporating 32 additional GWAS results for complex diseases and traits in Japanese individuals, we further highlighted pleiotropy, genetic correlations, and cell-type specificity across quantitative traits and diseases, which substantially expands the current understanding of the associated genetics and biology. This study identified both shared polygenic effects and cell-type specificity, represented by the genetic links among clinical measurements, complex diseases, and relevant cell types. Our findings demonstrate that even without prior biological knowledge of cross-phenotype relationships, genetics corresponding to clinical measurements successfully recapture those measurements' relevance to diseases, and thus can contribute to the elucidation of unknown etiology and pathogenesis.