Tuesday Dec 20, 2022
Lead Story: Genetic diversity fuels gene discovery for tobacco and alcohol use
Genetic diversity fuels gene discovery for tobacco and alcohol use
Nature
This study leverages global genetic diversity across 3.4 million individuals from four major clines of global ancestry 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. The authors found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the associated variants 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.