2型糖尿病的遗传学:来自大规模研究的启示

IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Current Diabetes Reports Pub Date : 2022-05-01 Epub Date: 2022-03-19 DOI:10.1007/s11892-022-01462-3
Natalie DeForest, Amit R Majithia
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引用次数: 22

摘要

综述目的:2型糖尿病(T2D)是一种多因素、遗传性综合征,其特征是胰岛素分泌受损和胰岛素抵抗导致葡萄糖稳态失调。遗传关联研究已经成功地确定了数百个涉及疾病发病机制的许多基因的T2D风险位点。在这篇综述中,我们提供了近3年来最近的T2D遗传研究的概述,特别关注样本量和祖先多样性对遗传发现的影响,并讨论了遗传风险评分(GRS)用于T2D风险预测的最新工作和局限性。最近的发现:最近对T2D的大规模、多祖先遗传研究已经确定了500多个新的风险位点。标记这些新位点的遗传变异(即单核苷酸多态性(SNPs))通常比以前发现的位点具有更小的效应大小。包括来自不同祖先背景的样本显示,一些特定的祖先基因座被共同变异标记,但总体而言,大多数发现的基因座在祖先中是共同的。纳入常见变异GRS,即使有数百个基因座,也不会显著提高T2D风险预测,高于标准临床风险因素(如年龄和家族史)。T2D的常见变异关联研究目前已经确定了700多个T2D风险位点,其中一半是在过去3年发现的。这些最近的研究表明,包含祖先多样化的样本可以增强基因座发现,提高GRS用于T2D风险预测的准确性。然而,基于常见变异的GRS对标准临床危险因素的风险预测只有最低限度的提高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetics of Type 2 Diabetes: Implications from Large-Scale Studies.

Purpose of review: Type 2 diabetes (T2D) is a multifactorial, heritable syndrome characterized by dysregulated glucose homeostasis that results from impaired insulin secretion and insulin resistance. Genetic association studies have successfully identified hundreds of T2D risk loci implicating many genes in disease pathogenesis. In this review, we provide an overview of the recent T2D genetic studies from the past 3 years with particular focus on the effects of sample size and ancestral diversity on genetic discovery as well as discuss recent work on the use and limitations of genetic risk scores (GRS) for T2D risk prediction.

Recent findings: Recent large-scale, multi-ancestry genetic studies of T2D have identified over 500 novel risk loci. The genetic variants (i.e., single nucleotide polymorphisms (SNPs)) marking these novel loci in general have smaller effect sizes than previously discovered loci. Inclusion of samples from diverse ancestral backgrounds shows a few ancestry specific loci marked by common variants, but overall, the majority of loci discovered are common across ancestries. Inclusion of common variant GRS, even with hundreds of loci, does not substantially increase T2D risk prediction over standard clinical risk factors such as age and family history. Common variant association studies of T2D have now identified over 700 T2D risk loci, half of which have been discovered in the past 3 years. These recent studies demonstrate that inclusion of ancestrally diverse samples can enhance locus discovery and improve accuracy of GRS for T2D risk prediction. GRS based on common variants, however, only minimally enhances risk prediction over standard clinical risk factors.

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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
52
审稿时长
6-12 weeks
期刊介绍: The goal of this journal is to publish cutting-edge reviews on subjects pertinent to all aspects of diabetes epidemiology, pathophysiology, and management. We aim to provide incisive, insightful, and balanced contributions from leading experts in each relevant domain that will be of immediate interest to a wide readership of clinicians, basic scientists, and translational investigators. We accomplish this aim by appointing major authorities to serve as Section Editors in key subject areas across the discipline. Section Editors select topics to be reviewed by leading experts who emphasize recent developments and highlight important papers published over the past year on their topics, in a crisp and readable format. We also provide commentaries from well-known figures in the field, and an Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.
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