Trans-ethnic fine mapping identifies a novel independent locus at the 3′ end of CDKAL1 and novel variants of several susceptibility loci for type 2 diabetes in a Han Chinese population

AIMS/HYPOTHESIS: Candidate gene and genome-wide association studies have identified ∼60 susceptibility loci for type 2 diabetes. A majority of these loci have been discovered and tested only in European populations. The aim of this study was to assess the presence and extent of trans-ethnic effects of these loci in an East Asian population. METHODS: A total of 9,335 unrelated Chinese Han individuals, including 4,535 with type 2 diabetes and 4,800 non-diabetic ethnically matched controls, were genotyped using the Illumina 200K Metabochip. We tested 50 established loci for type 2 diabetes and related traits (fasting glucose, fasting insulin, 2 h glucose). Disease association with the additive model of inheritance was analysed with logistic regression. RESULTS: We found that 14 loci significantly transferred to the Chinese population, with two loci (p = 5.7 × 10(−12) for KCNQ1; p = 5.0 × 10(−8) for CDKN2A/B-CDKN2BAS) reaching independent genome-wide statistical significance. Five of these 14 loci had similar lead single-nucleotide polymorphisms (SNPs) as were found in the European studies while the other nine were different. Further stepwise conditional analysis identified a total of seven secondary signals and an independent novel locus at the 3′ end of CDKAL1. CONCLUSIONS/INTERPRETATION: These results suggest that many loci associated with type 2 diabetes are commonly shared between European and Chinese populations. Identification of population-specific SNPs may increase our understanding of the genetic architecture underlying type 2 diabetes in different ethnic populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-013-3047-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users.