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. 2025 Feb;47(2):235-243.
doi: 10.1007/s13258-024-01602-x. Epub 2024 Dec 18.

Identification of genetic loci enriched in obese or lean T2D cases in the Korean population

Eun Bi Lim  1 , Yoon Shin Cho  2   3   4
Affiliations

Identification of genetic loci enriched in obese or lean T2D cases in the Korean population

Eun Bi Lim et al. Genes Genomics. 2025 Feb.

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: Meta-analysis combining the discovery and replication stages detected two variants with genome-wide significance: rs2356138 [P = 2.8 × 10-8, OR = 2.06 (1.59-2.65)] in obese T2D subjects and rs9295478 [P = 2.5 × 10-9, 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.

Conclusion: 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.

Keywords: Body mass index; Genome-wide association study; Obesity; Single-nucleotide polymorphism; Type 2 diabetes.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no conflict of interest. Ethics approval and consent to participate: This study was approved by the Institutional Review Board (HIRB-2023-047-CR) of Hallym University. Informed consent was obtained from all study subjects.

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