Genetic diversity fuels gene discovery for tobacco and alcohol use

23andMe Research Team, The Biobank Japan Project

研究成果: ジャーナルへの寄稿学術誌査読

80 被引用数 (Scopus)

抄録

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

本文言語英語
ページ(範囲)720-724
ページ数5
ジャーナルNature
612
7941
DOI
出版ステータス出版済み - 12月 22 2022

!!!All Science Journal Classification (ASJC) codes

  • 一般

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