Home > Genetic diversity fuels gene discovery for tobacco and alcohol use.

Saunders, Gretchen R B and Wang, Xingyan and Chen, Fang and Jang, Seon-Kyeong and Liu, Mengzhen and Wang, Chen and Gao, Shuang and Jiang, Yu and Khunsriraksakul, Chachrit and Otto, Jacqueline M and Addison, Clifton and Akiyama, Masato and Albert, Christine M and Aliev, Fazil and Alonso, Alvaro and Arnett, Donna K and Ashley-Koch, Allison E and Ashrani, Aneel A and Barnes, Kathleen C and Barr, R Graham and Bartz, Traci M and Becker, Diane M and Bielak, Lawrence F and Benjamin, Emelia J and Bis, Joshua C and Bjornsdottir, Gyda and Blangero, John and Bleecker, Eugene R and Boardman, Jason D and Boerwinkle, Eric and et al, . (2022) Genetic diversity fuels gene discovery for tobacco and alcohol use. Nature, 612, pp. 720-724. doi: 10.1038/s41586-022-05477-4.

External website: https://www.nature.com/articles/s41586-022-05477-4

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 injury. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries. 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.

Item Type
Publication Type
International, Open Access, Article
Drug Type
Alcohol, Tobacco / Nicotine
Intervention Type
Screening / Assessment
7 December 2022
Identification #
doi: 10.1038/s41586-022-05477-4
Page Range
pp. 720-724

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