Utility of Diabetes Type-Specific Genetic Risk Scores for the Classification of Diabetes Type Among Multiethnic Youth
Utility of Diabetes Type-Specific Genetic Risk Scores for the Classification of Diabetes Type Among Multiethnic Youth
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DOI：
10.2337/dc20-2872
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发表时间：
2022-05-01
期刊：
影响因子：
16.2
通讯作者：
Dabelea, Dana
中科院分区：
文献类型：
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作者：
Oram, Richard A.;Sharp, Seth A.;Dabelea, Dana
目的遗传风险评分 (GRS) 有助于对欧洲白人成年人群的糖尿病类型进行分类。我们的目的是评估 GRS 在美国不同种族/民族的青少年糖尿病类型分类中的效用。研究设计和方法我们在青少年糖尿病研究研究中对 2,045 名个体生成了 1 型糖尿病 (T1D)(-) 和 2 型糖尿病 (T2D) 特异性 GRS。我们评估了按糖尿病自身抗体阳性或阴性 (DAA(+/-))、胰岛素敏感性 (IS) 或胰岛素抵抗 (IR) 以及自我报告的种族/民族（白人、黑人、西班牙裔等）分层的遗传风险分布。RESULTST1D 和 T2D GRS 是病因类型的强有力的独立预测因子。 T1D GRS 在 DAA(+)/IS 组中最高，在 DAA(-)/IR 组中最低，与 T2D GRS 呈反比关系。所有种族/族裔群体的歧视都相似，但分数分布存在差异。按组合遗传风险进行聚类显示，DAA(+)/IR 和 DAA(-)/IS 个体患 T1D 的可能性高于 T2D。在 DAA(-) 个体中，T1D 的遗传概率确定了最有可能进展为绝对胰岛素缺乏的个体。结论：在美国青年队列中，糖尿病类型特异性 GRS 是跨种族/族裔群体糖尿病类型的一致预测因子，但未来的工作需要考虑按血统划分的 GRS 分布差异。 T1D 和 T2D GRS 对于 DAA(-) 儿童的分类可能特别有用。
OBJECTIVEGenetic risk scores (GRS) aid classification of diabetes type in White European adult populations. We aimed to assess the utility of GRS in the classification of diabetes type among racially/ethnically diverse youth in the U.S.RESEARCH DESIGN AND METHODSWe generated type 1 diabetes (T1D)(-) and type 2 diabetes (T2D)-specific GRS in 2,045 individuals from the SEARCH for Diabetes in Youth study. We assessed the distribution of genetic risk stratified by diabetes autoantibody positive or negative (DAA(+/-)) and insulin sensitivity (IS) or insulin resistance (IR) and self-reported race/ethnicity (White, Black, Hispanic, and other).RESULTST1D and T2D GRS were strong independent predictors of etiologic type. The T1D GRS was highest in the DAA(+)/IS group and lowest in the DAA(-)/IR group, with the inverse relationship observed with the T2D GRS. Discrimination was similar across all racial/ethnic groups but showed differences in score distribution. Clustering by combined genetic risk showed DAA(+)/IR and DAA(-)/IS individuals had a greater probability of T1D than T2D. In DAA(-) individuals, genetic probability of T1D identified individuals most likely to progress to absolute insulin deficiency.CONCLUSIONSDiabetes type-specific GRS are consistent predictors of diabetes type across racial/ethnic groups in a U.S. youth cohort, but future work needs to account for differences in GRS distribution by ancestry. T1D and T2D GRS may have particular utility for classification of DAA(-) children.