Genetics of Type 2 Diabetes: Implications from Large-Scale Studies.

Genetics of Type 2 Diabetes: Implications from Large-Scale Studies.
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DOI:
10.1007/s11892-022-01462-3
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发表时间:
2022-05
影响因子:
4.2
通讯作者:
Majithia, Amit R.
Majithia, Amit R.
中科院分区:
医学2区
文献类型:
--
作者:
DeForest, Natalie;Majithia, Amit R.

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2型糖尿病(T2D)是一种多因素遗传综合征,其特征是由胰岛素分泌受损和胰岛素抵抗引起的葡萄糖稳态失调。遗传关联研究已经成功地鉴定了数百个T2D风险位点,这些位点涉及疾病发病机制中的许多基因。在这篇综述中,我们提供了一个概述,最近的T2D遗传研究从过去的3年,特别侧重于样本量和祖先的多样性对遗传发现的影响,以及讨论最近的工作的使用和限制遗传风险评分(GRS)的T2D风险预测。最近的大规模多祖先T2D遗传研究已经确定了500多个新的风险位点。遗传变异(即,标记这些新基因座的单核苷酸多态性(SNP)通常具有比先前发现的基因座更小的效应大小。包含来自不同祖先背景的样本显示了一些祖先特异性基因座,其标记为常见变体,但总体而言,所发现的大多数基因座在祖先中是常见的。纳入常见变异GRS,即使有数百个基因座,也不会显著增加T2D风险预测超过标准临床风险因素,如年龄和家族史。T2D的常见变异关联研究现已确定了700多个T2D风险位点,其中一半是在过去3年中发现的。这些最近的研究表明,包括祖先不同的样本可以增强基因座发现,并提高GRS对T2D风险预测的准确性。然而,基于常见变异的GRS仅最低限度地增强了对标准临床风险因素的风险预测。
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 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.
DOI: 10.1002/gepi.22083
发表时间: 2017-12
影响因子: 2.1
作者:
Márquez-Luna C;Loh PR;South Asian Type 2 Diabetes (SAT2D) Consortium;SIGMA Type 2 Diabetes Consortium;Price AL
通讯作者: Price AL
评估18种常见遗传变异的综合遗传变异对2型糖尿病风险的综合影响。
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发表时间: 2008-11
期刊: Diabetes
影响因子: 7.7
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发表时间: 2010-02
期刊: Diabetes care
影响因子: 16.2
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