4.0 Article

Analysis of Glucocorticoid-Related Genes Reveal CCHCR1 as a New Candidate Gene for Type 2 Diabetes

期刊

JOURNAL OF THE ENDOCRINE SOCIETY
卷 4, 期 11, 页码 -

出版社

ENDOCRINE SOC
DOI: 10.1210/jendso/bvaa121

关键词

corticosteroid; diabetes; genetics

资金

  1. Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources)
  2. Harvard University
  3. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1F32 DK115086-01A1, K24 DK110550, 1DP3 DK111906, 1R01 DK122586]
  4. Wagner Fellowship Fund
  5. Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]

向作者/读者索取更多资源

Glucocorticoids have multiple therapeutic benefits and are used both for immunosuppression and treatment purposes. Notwithstanding their benefits, glucocorticoid use often leads to hyperglycemia. Owing to the pathophysiologic overlap in glucocorticoid-induced hyperglycemia (GIH) and type 2 diabetes (T2D), we hypothesized that genetic variation in glucocorticoid pathways contributes to T2D risk. To determine the genetic contribution of glucocorticoid action on T2D risk, we conducted multiple genetic studies. First, we performed gene-set enrichment analyses on 3 collated glucocorticoid-related gene sets using publicly available genome-wide association and whole-exome data and demonstrated that genetic variants in glucocorticoid-related genes are associated with T2D and related glycemic traits. To identify which genes are driving this association, we performed gene burden tests using whole-exome sequence data. We identified 20 genes within the glucocorticoid-related gene sets that are nominally enriched forT2D-associated protein-coding variants. The most significant association was found in coding variants in coiled-coil a-helical rod protein 1 (CCHCR1) in the HLA region (P = .001). Further analyses revealed that noncoding variants near CCHCR1 are also associated with T2D at genome-wide significance (P = 7.70 x 10(-14)), independent of type 1 diabetes HLA risk. Finally, gene expression and colocalization analyses demonstrate that variants associated with increased T2D risk are also associated with decreased expression of CCHCR1 in multiple tissues, implicating this gene as a potential effector transcript at this locus. Our discovery of a genetic link between glucocorticoids and T2D findings support the hypothesis that T2D and GIH may have shared underlying mechanisms.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.0
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据