title: A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci.
abstract: Diabetes impacts approximately 200 million people worldwide, of whom approximately 10% are affected by type 1 diabetes (T1D). The application of genome-wide association studies (GWAS) has robustly revealed dozens of genetic contributors to the pathogenesis of T1D, with the most recent meta-analysis identifying in excess of 40 loci. To identify additional genetic loci for T1D susceptibility, we examined associations in the largest meta-analysis to date between the disease and ∼2.54 million SNPs in a combined cohort of 9,934 cases and 16,956 controls. Targeted follow-up of 53 SNPs in 1,120 affected trios uncovered three new loci associated with T1D that reached genome-wide significance. The most significantly associated SNP (rs539514, P = 5.66×10⁻¹¹) resides in an intronic region of the LMO7 (LIM domain only 7) gene on 13q22. The second most significantly associated SNP (rs478222, P = 3.50×10⁻⁹ resides in an intronic region of the EFR3B (protein EFR3 homolog B) gene on 2p23; however, the region of linkage disequilibrium is approximately 800 kb and harbors additional multiple genes, including NCOA1, C2orf79, CENPO, ADCY3, DNAJC27, POMC, and DNMT3A. The third most significantly associated SNP (rs924043, P = 8.06×10⁻⁹ lies in an intergenic region on 6q27, where the region of association is approximately 900 kb and harbors multiple genes including WDR27, C6orf120, PHF10, TCTE3, C6orf208, LOC154449, DLL1, FAM120B, PSMB1, TBP, and PCD2. These latest associated regions add to the growing repertoire of gene networks predisposing to T1D.
authors: The Center for Applied Genomics, The Children's Hospital Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors: Jonathan P
authors: JP
authors: Bradfield
authors: Hui-Qi
authors: HQ
authors: Qu
authors: Kai
authors: K
authors: Wang
authors: Haitao
authors: H
authors: Zhang
authors: Patrick M
authors: PM
authors: Sleiman
authors: Cecilia E
authors: CE
authors: Kim
authors: Frank D
authors: FD
authors: Mentch
authors: Haijun
authors: H
authors: Qiu
authors: Joseph T
authors: JT
authors: Glessner
authors: Kelly A
authors: KA
authors: Thomas
authors: Edward C
authors: EC
authors: Frackelton
authors: Rosetta M
authors: RM
authors: Chiavacci
authors: Marcin
authors: M
authors: Imielinski
authors: Dimitri S
authors: DS
authors: Monos
authors: Rahul
authors: R
authors: Pandey
authors: Marina
authors: M
authors: Bakay
authors: Struan F A
authors: SF
authors: Grant
authors: Constantin
authors: C
authors: Polychronakos
authors: Hakon
authors: H
authors: Hakonarson
mesh_terms: D015331:Cohort Studies; D021901:DNA, Intergenic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017385:Sequence Homology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D021901:DNA, Intergenic; D060588:LIM Domain Proteins; C116184:LMO7 protein, human; D014157:Transcription Factors