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, 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.

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.