小柯机器人

美国明尼苏达大学Scott Vrieze等研究人员合作发现，遗传多样性推动烟草和酒精使用的基因发现。2022年12月7日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员利用来自全球四大群体（约21%为非欧洲人）340万个体的全球遗传多样性，为发现和精确定位与烟草和酒精使用相关的基因组位点提供了线索。研究人员通过祖先明确的全基因组关联研究告知这些位点的功能，并评估多基因风险的遗传结构和预测能力。研究人员发现，样本量和遗传多样性的增加改善了基因座的识别和精细绘图的分辨率，3823个相关变体（来自2143个基因座）中的大部分在不同血统维度上显示出一致的效应大小。然而，在一个血统中开发的多基因风险评分在其他血统中表现不佳，这突出表明继续需要增加不同血统的样本量来实现多基因预测的任何潜在好处。

据介绍，烟草和酒精的使用是可遗传的行为，分别与全世界15%和5.3%的死亡有关，主要是因为疾病和伤害的风险广泛增加。这些物质的使用遍及全球，但全基因组关联研究主要集中在欧洲血统的个体上。

附：英文原文

Title: Genetic diversity fuels gene discovery for tobacco and alcohol use

Author: Saunders, Gretchen R. B., Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M., Addison, Clifton, Akiyama, Masato, Albert, Christine M., Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K., Ashley-Koch, Allison E., Ashrani, Aneel A., Barnes, Kathleen C., Barr, R. Graham, Bartz, Traci M., Becker, Diane M., Bielak, Lawrence F., Benjamin, Emelia J., Bis, Joshua C., Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R., Boardman, Jason D., Boerwinkle, Eric, Boomsma, Dorret I., Boorgula, Meher Preethi, Bowden, Donald W., Brody, Jennifer A., Cade, Brian E., Chasman, Daniel I., Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H., Choquet, Hlne, Cole, John W., Cornelis, Marilyn C., Cucca, Francesco, Curran, Joanne E., de Andrade, Mariza, Dick, Danielle M., Docherty, Anna R., Duggirala, Ravindranath, Eaton, Charles B., Ehringer, Marissa A., Esko, Tnu, Faul, Jessica D., Silva, Lilian Fernandes, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I., Gabrielsen, Maiken E., Garrett, Melanie E., Gharib, Sina A., Gieger, Christian, Gillespie, Nathan, Glahn, David C., Gordon, Scott D., Gu, Charles C.

Issue&Volume: 2022-12-07

Abstract: 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 injury1,2,3,4. 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.

DOI: 10.1038/s41586-022-05477-4

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

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html