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Genome-wide association study identifies three novel loci for type 2 diabetes.

TitleGenome-wide association study identifies three novel loci for type 2 diabetes.
Publication TypeJournal Article
Year of Publication2014
AuthorsHara K, Fujita H, Johnson TA, Yamauchi T, Yasuda K, Horikoshi M, Peng C, Hu C, Ma RCW, Imamura M, Iwata M, Tsunoda T, Morizono T, Shojima N, So WYee, Leung TFan, Kwan P, Zhang R, Wang J, Yu W, Maegawa H, Hirose H, Kaku K, Ito C, Watada H, Tanaka Y, Tobe K, Kashiwagi A, Kawamori R, Jia W, Chan JCN, Teo YYing, Shyong TE, Kamatani N, Kubo M, Maeda S
Secondary AuthorsKadowaki T
Corporate AuthorsDIAGRAM Consortium
JournalHum Mol Genet
Volume23
Issue1
Pagination239-46
Date Published2014 Jan 01
ISSN1460-2083
KeywordsDiabetes Mellitus, Type 2, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genome-Wide Association Study, Guanine Nucleotide Dissociation Inhibitors, Haplotypes, Humans, Leptin, MicroRNAs, Monocarboxylic Acid Transporters, Polymorphism, Single Nucleotide
Abstract

Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.

DOI10.1093/hmg/ddt399
Alternate JournalHum Mol Genet
PubMed ID23945395
Grant List090532 / / Wellcome Trust / United Kingdom
MC_U106179471 / / Medical Research Council / United Kingdom
MC_UU_12015/1 / / Medical Research Council / United Kingdom
MC_UU_12015/4 / / Medical Research Council / United Kingdom