Lim Eun Bi, Cho Yoon Shin
Department of Biomedical Science, Hallym University, Chuncheon, Gangwon State, 24252, Republic of Korea.
Department of Neuroscience, Hallym University College of Medicine, Chuncheon, Gangwon State, 24252, Republic of Korea.
Genes Genomics. 2025 Feb;47(2):235-243. doi: 10.1007/s13258-024-01602-x. Epub 2024 Dec 18.
Obesity causes many complex diseases including type 2 diabetes (T2D). Obesity increases the risk of T2D in Europeans, but there are many non-obese (lean) T2D patients in East Asia.
To discover genetic factors enriched in obese or lean T2D patients, we conducted a genome-wide association (GWA) analysis for T2D stratified by BMI in the Korean population.
In the discovery stage, 654 and 247 individuals classified as obese (BMI > 25) and lean (BMI < 23) T2D patients, respectively, were compared with 3,842 control subjects for GWA analysis. Several BMI-stratified T2D variants detected in the discovery stage were further tested in the replication stage, which included 402 obese and 220 lean T2D cases, and 3,615 controls.
Meta-analysis combining the discovery and replication stages detected two variants with genome-wide significance: rs2356138 [P = 2.8 × 10, OR = 2.06 (1.59-2.65)] in obese T2D subjects and rs9295478 [P = 2.5 × 10, OR = 1.61 (1.38-1.88)] in lean ones. The SNP rs9295478 is located in CDKAL1, a well-known T2D gene previously identified in several GWA studies. Meanwhile, the SNP rs2356138 is a previously unknown variant located in PKP4.
We discovered genetic loci enriched in obese or lean T2D patients in the Korean population. Our findings should facilitate more effective control of T2D in Koreans.
肥胖会引发包括2型糖尿病（T2D）在内的多种复杂疾病。肥胖会增加欧洲人患T2D的风险，但东亚有许多非肥胖（瘦型）T2D患者。
为了发现肥胖或瘦型T2D患者中富集的遗传因素，我们在韩国人群中对按体重指数（BMI）分层的T2D进行了全基因组关联（GWA）分析。
在发现阶段，分别将654例和247例被分类为肥胖（BMI＞25）和瘦型（BMI＜23）的T2D患者与3842例对照受试者进行GWA分析。在发现阶段检测到的几个按BMI分层的T2D变异在复制阶段进一步进行检测，复制阶段包括402例肥胖和220例瘦型T2D病例以及3615例对照。
结合发现阶段和复制阶段的荟萃分析检测到两个具有全基因组显著性的变异：肥胖T2D受试者中的rs2356138 [P = 2.8×10，比值比（OR）= 2.06（1.59 - 2.65）] 和瘦型受试者中的rs9295478 [P = 2.5×10，OR = 1.61（1.38 - 1.88）]。单核苷酸多态性（SNP）rs9295478位于CDKAL1中，CDKAL1是先前在多项GWA研究中确定的一个著名的T2D基因。同时，SNP rs2356138是位于PKP4中的一个先前未知的变异。
我们在韩国人群中发现了肥胖或瘦型T2D患者中富集的遗传位点。我们的发现应有助于更有效地控制韩国人的T2D。
