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A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci

Bradfield, Jonathan P ; Qu, Hui-Qi ; Wang, Kai ; Zhang, Haitao ; Sleiman, Patrick M ; Kim, Cecilia E ; Mentch, Frank D ; Qiu, Haijun ; Glessner, Joseph T ; Thomas, Kelly A ; Frackelton, Edward C ; Chiavacci, Rosetta M ; Imielinski, Marcin ; Monos, Dimitri S ; Pandey, Rahul ; Bakay, Marina ; Grant, Struan F A ; Polychronakos, Constantin ; Hakonarson, Hakon McCarthy, Mark I.

PLoS genetics, 2011-09, Vol.7 (9), p.e1002293-e1002293 [Revista revisada por pares]

United States: Public Library of Science

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A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci
Autor: Bradfield, Jonathan P ; Qu, Hui-Qi ; Wang, Kai ; Zhang, Haitao ; Sleiman, Patrick M ; Kim, Cecilia E ; Mentch, Frank D ; Qiu, Haijun ; Glessner, Joseph T ; Thomas, Kelly A ; Frackelton, Edward C ; Chiavacci, Rosetta M ; Imielinski, Marcin ; Monos, Dimitri S ; Pandey, Rahul ; Bakay, Marina ; Grant, Struan F A ; Polychronakos, Constantin ; Hakonarson, Hakon
McCarthy, Mark I.
Materias: Biology ; Cardiovascular diseases ; Chromosomes ; Cohort Studies ; Complications and side effects ; Diabetes ; Diabetes Mellitus, Type 1 - genetics ; Disease ; DNA, Intergenic ; Female ; Genetic aspects ; Genetic Loci ; Genetic Predisposition to Disease ; Genetics ; Genome-Wide Association Study ; Genomes ; Genomics ; Humans ; Kidney diseases ; LIM Domain Proteins - genetics ; Linkage Disequilibrium ; Male ; Meta-analysis ; Polymorphism, Single Nucleotide - genetics ; Risk factors ; Sequence Homology ; Single nucleotide polymorphisms ; Transcription Factors - genetics ; Type 1 diabetes
Es parte de: PLoS genetics, 2011-09, Vol.7 (9), p.e1002293-e1002293
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Conceived and designed the experiments: JPB H-QQ SFAG CP HH. Performed the experiments: JPB CEK KAT ECF RP MB. Analyzed the data: JPB H-QQ KW HZ PMS FDM HQ JTG MI SFAG. Contributed reagents/materials/analysis tools: RMC DSM SFAG CP HH. Wrote the paper: JPB H-QQ SFAG CP HH.
Current address: Division of Epidemiology School of Public Health, University of Texas Health Science Center, Houston, Texas, United States of America
Descripción: 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.
Editor: United States: Public Library of Science
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A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci

United States: Public Library of Science

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