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Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

Author

Listed:
  • Maggie C Y Ng
  • Daniel Shriner
  • Brian H Chen
  • Jiang Li
  • Wei-Min Chen
  • Xiuqing Guo
  • Jiankang Liu
  • Suzette J Bielinski
  • Lisa R Yanek
  • Michael A Nalls
  • Mary E Comeau
  • Laura J Rasmussen-Torvik
  • Richard A Jensen
  • Daniel S Evans
  • Yan V Sun
  • Ping An
  • Sanjay R Patel
  • Yingchang Lu
  • Jirong Long
  • Loren L Armstrong
  • Lynne Wagenknecht
  • Lingyao Yang
  • Beverly M Snively
  • Nicholette D Palmer
  • Poorva Mudgal
  • Carl D Langefeld
  • Keith L Keene
  • Barry I Freedman
  • Josyf C Mychaleckyj
  • Uma Nayak
  • Leslie J Raffel
  • Mark O Goodarzi
  • Y-D Ida Chen
  • Herman A Taylor Jr.
  • Adolfo Correa
  • Mario Sims
  • David Couper
  • James S Pankow
  • Eric Boerwinkle
  • Adebowale Adeyemo
  • Ayo Doumatey
  • Guanjie Chen
  • Rasika A Mathias
  • Dhananjay Vaidya
  • Andrew B Singleton
  • Alan B Zonderman
  • Robert P Igo Jr.
  • John R Sedor
  • the FIND Consortium
  • Edmond K Kabagambe
  • David S Siscovick
  • Barbara McKnight
  • Kenneth Rice
  • Yongmei Liu
  • Wen-Chi Hsueh
  • Wei Zhao
  • Lawrence F Bielak
  • Aldi Kraja
  • Michael A Province
  • Erwin P Bottinger
  • Omri Gottesman
  • Qiuyin Cai
  • Wei Zheng
  • William J Blot
  • William L Lowe
  • Jennifer A Pacheco
  • Dana C Crawford
  • the eMERGE Consortium
  • the DIAGRAM Consortium
  • Elin Grundberg
  • the MuTHER Consortium
  • Stephen S Rich
  • M Geoffrey Hayes
  • Xiao-Ou Shu
  • Ruth J F Loos
  • Ingrid B Borecki
  • Patricia A Peyser
  • Steven R Cummings
  • Bruce M Psaty
  • Myriam Fornage
  • Sudha K Iyengar
  • Michele K Evans
  • Diane M Becker
  • W H Linda Kao
  • James G Wilson
  • Jerome I Rotter
  • Michèle M Sale
  • Simin Liu
  • Charles N Rotimi
  • Donald W Bowden
  • for the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium

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

Suggested Citation

  • Maggie C Y Ng & Daniel Shriner & Brian H Chen & Jiang Li & Wei-Min Chen & Xiuqing Guo & Jiankang Liu & Suzette J Bielinski & Lisa R Yanek & Michael A Nalls & Mary E Comeau & Laura J Rasmussen-Torvik &, 2014. "Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes," PLOS Genetics, Public Library of Science, vol. 10(8), pages 1-14, August.
    • Handle: RePEc:plo:pgen00:1004517
    DOI: 10.1371/journal.pgen.1004517
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    References listed on IDEAS

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    2. Jiajin Li & Brandon Jew & Lingyu Zhan & Sungoo Hwang & Giovanni Coppola & Nelson B Freimer & Jae Hoon Sul, 2019. "ForestQC: Quality control on genetic variants from next-generation sequencing data using random forest," PLOS Computational Biology, Public Library of Science, vol. 15(12), pages 1-30, December.

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