Diabetologia ( IF 8.4 ) Pub Date : 2024-09-30 , DOI: 10.1007/s00125-024-06277-3 Shuai Liu, Jingjing Zhu, Hua Zhong, Chong Wu, Haoran Xue, Burcu F. Darst, Xiuqing Guo, Peter Durda, Russell P. Tracy, Yongmei Liu, W. Craig Johnson, Kent D. Taylor, Ani W. Manichaikul, Mark O. Goodarzi, Robert E. Gerszten, Clary B. Clish, Yii-Der Ida Chen, Heather Highland, Christopher A. Haiman, Christopher R. Gignoux, Leslie Lange, David V. Conti, Laura M. Raffield, Lynne Wilkens, Loïc Le Marchand, Kari E. North, Kristin L. Young, Ruth J. Loos, Steve Buyske, Tara Matise, Ulrike Peters, Charles Kooperberg, Alexander P. Reiner, Bing Yu, Eric Boerwinkle, Quan Sun, Mary R. Rooney, Justin B. Echouffo-Tcheugui, Martha L. Daviglus, Qibin Qi, Nicholas Mancuso, Changwei Li, Youping Deng, Alisa Manning, James B. Meigs, Stephen S. Rich, Jerome I. Rotter, Lang Wu
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Aims/hypothesis
Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.
Methods
Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were applied to genome-wide association study summary statistics of 250,127 type 2 diabetes cases and 1,222,941 controls from different racial and ethnic populations.
Results
We identified three, 44 and one protein associated with type 2 diabetes risk in Asian, European and Hispanic/Latino populations, respectively. Meta-analysis identified 40 proteins associated with type 2 diabetes risk across the populations, including well-established as well as novel proteins not yet implicated in type 2 diabetes development.
Conclusions/interpretation
Our study improves our understanding of the aetiology of type 2 diabetes in diverse populations.
Data availability
The summary statistics of multi-ethnic type 2 diabetes GWAS of MVP, DIAMANTE, Biobank Japan and other studies are available from The database of Genotypes and Phenotypes (dbGaP) under accession number phs001672.v3.p1. MESA genetic, proteome and covariate data can be accessed through dbGaP under phs000209.v13.p3. All code is available on GitHub (https://github.com/Arthur1021/MESA-1K-PWAS).
Graphical Abstract
中文翻译：
鉴定与不同种族和民族人群中 2 型糖尿病风险相关的蛋白质
目标/假设
多项研究报告了欧洲人群中特定蛋白质与 2 型糖尿病风险之间的关联。为了更好地了解蛋白质在不同人群的 2 型糖尿病病因学中所发挥的作用，我们使用跨越四个种族和民族的遗传仪器进行了一项大型蛋白质组关联研究：亚洲人；西班牙裔/拉丁裔；和欧洲的。
方法
Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were applied to genome-wide association study summary statistics of 250,127 type 2 diabetes cases and 1,222,941 controls from different racial and ethnic populations.
结果
我们在亚洲、欧洲和西班牙/拉丁裔人群中分别鉴定了 3 种、44 种和 1 种与 2 型糖尿病风险相关的蛋白质。荟萃分析确定了 40 种与人群中 2 型糖尿病风险相关的蛋白质，包括已确定的蛋白质以及尚未与 2 型糖尿病发展相关的新型蛋白质。
结论/解释
我们的研究提高了我们对不同人群 2 型糖尿病病因学的了解。
数据可用性
MVP、DIAMANTE、Biobank Japan 等研究的多种族 2 型糖尿病 GWAS 汇总统计可从基因型和表型数据库 (dbGaP) 获取，登录号为 phs001672.v3.p1。 MESA 遗传、蛋白质组和协变量数据可以通过 phs000209.v13.p3 下的 dbGaP 访问。所有代码均可在 GitHub (https://github.com/Arthur1021/MESA-1K-PWAS) 上获取。
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