Identification of proteins associated with type 2 diabetes risk in diverse racial and ethnic populations.

IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia 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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引用次数: 0

Abstract

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 ).

Abstract Image

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鉴定不同种族和民族人群中与 2 型糖尿病风险相关的蛋白质。

目的/假设：有几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 型糖尿病病因中扮演的角色，我们使用基因工具对四个种族和民族群体进行了一项大型蛋白质组关联研究：方法：多种族动脉粥样硬化研究（MESA）的基因组和血浆蛋白质组数据涉及居住在美国的 182 名非洲人、69 名亚洲人、284 名西班牙裔/拉丁美洲人和 409 名欧洲人，我们利用这些数据建立了蛋白质预测模型，并使用了可能相关的顺式和反式 SNPs。这些模型被应用于对来自不同种族和民族的 250 127 例 2 型糖尿病病例和 1 222 941 例对照的全基因组关联研究汇总统计：结果：我们在亚裔、欧裔和拉美裔人群中分别发现了 3 种、44 种和 1 种与 2 型糖尿病风险相关的蛋白质。元分析确定了 40 种蛋白质与不同人群的 2 型糖尿病风险有关，其中包括已经证实的蛋白质以及尚未与 2 型糖尿病发病有关的新型蛋白质：我们的研究增进了我们对不同人群 2 型糖尿病病因的了解：MVP、DIAMANTE、Biobank Japan 和其他研究的多种族 2 型糖尿病 GWAS 的汇总统计数据可从基因型与表型数据库（dbGaP）获取，数据库登录号为 phs001672.v3.p1。MESA 基因、蛋白质组和协变量数据可通过 dbGaP 访问，登录号为 phs000209.v13.p3。所有代码均可在 GitHub ( https://github.com/Arthur1021/MESA-1K-PWAS ) 上获取。

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来源期刊

Diabetologia 医学-内分泌学与代谢

CiteScore

18.10

自引率

2.40%

发文量

193

审稿时长

1 months

期刊介绍： Diabetologia, the authoritative journal dedicated to diabetes research, holds high visibility through society membership, libraries, and social media. As the official journal of the European Association for the Study of Diabetes, it is ranked in the top quartile of the 2019 JCR Impact Factors in the Endocrinology & Metabolism category. The journal boasts dedicated and expert editorial teams committed to supporting authors throughout the peer review process.