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非裔美国人 2 型糖尿病的变异水平遗传力估计。

Variant level heritability estimates of type 2 diabetes in African Americans.

机构信息

Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.

Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.

出版信息

Sci Rep. 2024 Jun 18;14(1):14009. doi: 10.1038/s41598-024-64711-3.

Abstract

Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.

摘要

2 型糖尿病(T2D)是由遗传和环境因素共同引起的,与心肾并发症和死亡率的增加风险相关。尽管非裔美国人(AA)受该疾病的影响不成比例,但在 T2D 的遗传研究中,他们的代表性严重不足,并且在这个种族群体中很少计算出遗传力的估计值。本研究使用全基因组关联研究(GWAS)数据,并结合来自 Reasons for Geographic and Racial Differences in Stroke(REGARDS)研究、Genetics of Hypertension Associated Treatments(GenHAT)研究和 Electronic Medical Records and Genomics(eMERGE)网络的约 19300 名 AA 参与者的表型数据,我们使用两种方法估计了狭义遗传力:连锁不平衡调整的亲缘关系(LDAK)和全基因组复杂性状分析(GCTA)。两种方法的研究水平遗传力估计值,在调整年龄、性别和遗传祖先后,范围从 18%到 34%不等。总的来说,与之前的估计相比,本研究缩小了该种族群体 T2D 遗传力的预期范围,同时为正在进行的遗传发现工作提供了非裔美国人 T2D 遗传基础的新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/401a/11189523/16b4d7c979d5/41598_2024_64711_Fig1_HTML.jpg

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