Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Division of Academic General Pediatrics, Child Development and Community Health, University of California at San Diego, San Diego, California, USA.
Pediatr Obes. 2021 Jul;16(7):e12765. doi: 10.1111/ijpo.12765. Epub 2020 Dec 30.
The genetic underpinnings of glycemic traits have been understudied in adolescent and Hispanic/Latino (H/L) populations in comparison to adults and populations of European ancestry.
To identify genetic factors underlying glycemic traits in an adolescent H/L population.
We conducted a genome-wide association study (GWAS) of fasting glucose (FG) and fasting insulin (FI) in H/L adolescents from the Santiago Longitudinal Study.
We identified one novel variant positioned in the CSMD1 gene on chromosome 8 (rs77465890, effect allele frequency = 0.10) that was associated with FI (β = -0.299, SE = 0.054, p = 2.72×10 ) and was only slightly attenuated after adjusting for body mass index z-scores (β = -0.252, SE = 0.047, p = 1.03×10 ). We demonstrated directionally consistent, but not statistically significant results in African and Hispanic adults of the Population Architecture Using Genomics and Epidemiology Consortium. We also identified secondary signals for two FG loci after conditioning on known variants, which demonstrate allelic heterogeneity in well-known glucose loci.
Our results exemplify the importance of including populations with diverse ancestral origin and adolescent participants in GWAS of glycemic traits to uncover novel risk loci and expand our understanding of disease aetiology.
与成年人和欧洲血统人群相比，在青少年和西班牙裔/拉丁裔（H/L）人群中，血糖特征的遗传基础研究还不够充分。
在 H/L 青少年人群中确定血糖特征的遗传因素。
我们对圣地亚哥纵向研究中的 H/L 青少年进行了一项空腹血糖（FG）和空腹胰岛素（FI）的全基因组关联研究（GWAS）。
我们在 8 号染色体上发现了一个位于 CSMD1 基因内的新变异（rs77465890，效应等位基因频率=0.10），该变异与 FI 相关（β=-0.299，SE=0.054，p=2.72×10-5），且在调整体重指数 z 分数后略有减弱（β=-0.252，SE=0.047，p=1.03×10-3）。我们在基因与流行病学人群结构分析联盟的非洲裔和西班牙裔成年人中也观察到了方向一致但无统计学意义的结果。在已知变异的基础上，我们还鉴定了两个 FG 位点的次要信号，这些信号显示了已知葡萄糖位点的等位基因异质性。
我们的研究结果表明，在对血糖特征进行全基因组关联研究时，纳入具有不同祖先起源的人群和青少年参与者非常重要，这有助于发现新的风险位点，并扩展我们对疾病发病机制的认识。
