학술논문

Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.
Document Type
article
Author
Ng, Maggie CYShriner, DanielChen, Brian HLi, JiangChen, Wei-MinGuo, XiuqingLiu, JiankangBielinski, Suzette JYanek, Lisa RNalls, Michael AComeau, Mary ERasmussen-Torvik, Laura JJensen, Richard AEvans, Daniel SSun, Yan VAn, PingPatel, Sanjay RLu, YingchangLong, JirongArmstrong, Loren LWagenknecht, LynneYang, LingyaoSnively, Beverly MPalmer, Nicholette DMudgal, PoorvaLangefeld, Carl DKeene, Keith LFreedman, Barry IMychaleckyj, Josyf CNayak, UmaRaffel, Leslie JGoodarzi, Mark OChen, Y-D IdaTaylor, Herman ACorrea, AdolfoSims, MarioCouper, DavidPankow, James SBoerwinkle, EricAdeyemo, AdebowaleDoumatey, AyoChen, GuanjieMathias, Rasika AVaidya, DhananjaySingleton, Andrew BZonderman, Alan BIgo, Robert PSedor, John RFIND ConsortiumKabagambe, Edmond KSiscovick, David SMcKnight, BarbaraRice, KennethLiu, YongmeiHsueh, Wen-ChiZhao, WeiBielak, Lawrence FKraja, AldiProvince, Michael ABottinger, Erwin PGottesman, OmriCai, QiuyinZheng, WeiBlot, William JLowe, William LPacheco, Jennifer ACrawford, Dana CeMERGE ConsortiumDIAGRAM ConsortiumGrundberg, ElinMuTHER ConsortiumRich, Stephen SHayes, M GeoffreyShu, Xiao-OuLoos, Ruth JFBorecki, Ingrid BPeyser, Patricia ACummings, Steven RPsaty, Bruce MFornage, MyriamIyengar, Sudha KEvans, Michele KBecker, Diane MKao, WH LindaWilson, James GRotter, Jerome ISale, Michèle MLiu, SiminRotimi, Charles NBowden, Donald WMEta-analysis of type 2 DIabetes in African Americans Consortium
Source
PLoS genetics. 10(8)
Subject
FIND Consortium
eMERGE Consortium
DIAGRAM Consortium
MuTHER Consortium
MEta-analysis of type 2 DIabetes in African Americans Consortium
Humans
Diabetes Mellitus
Type 2
HMGA2 Protein
HLA-B27 Antigen
Polymorphism
Single Nucleotide
African Americans
Mutant Chimeric Proteins
KCNQ1 Potassium Channel
Genome-Wide Association Study
Transcription Factor 7-Like 2 Protein
Human Genome
Diabetes
Genetics
2.1 Biological and endogenous factors
Metabolic and endocrine
Developmental Biology
Language
Abstract
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)