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  • Title: 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.
    Author: Kuo JZ, Sheu WH, Assimes TL, Hung YJ, Absher D, Chiu YF, Mak J, Wang JS, Kwon S, Hsu CC, Goodarzi MO, Lee IT, Knowles JW, Miller BE, Lee WJ, Juang JM, Wang TD, Guo X, Taylor KD, Chuang LM, Hsiung CA, Quertermous T, Rotter JI, Chen YD.
    Journal: Diabetologia; 2013 Dec; 56(12):2619-28. PubMed ID: 24013783.
    Abstract:
    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.
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