Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin
Creators: name: Irvin, Marguerite R.
name: Franceschini, Nora
name: Eicher, John D.
name: Biggs, Mary L.
name: Vaidya, Dhananjay
name: Chen, Yii-Der Ida
name: Sims, Mario
name: Chen, Wei-Min
name: Tanaka, Toshiko
name: Rotter, Jerome I.
name: Porneala, Bianca C.
name: Pacheco, Jennifer A.
name: Liu, Simin
name: Li, Xiaohui
name: Couper, David J.
name: Morris, Andrew P.
name: Zonderman, Alan B.
name: Delaney, Joseph A.C.
name: Lowe, William L.
name: Evans, Daniel S.
name: Gottesman, Omri
name: Langefeld, Carl D.
name: Crawford, Dana C.
name: Loos, Ruth J.F.
name: Wren, Mary P.
name: Kao, W.H. Linda
name: Pankow, James S.
name: Jensen, Richard A.
name: Keller, Margaux F.
name: Rasmussen-Torvik, Laura J.
name: Guo, Xiuqing
name: Liu, Yongmei
name: Province, Michael A.
name: Mosley, Thomas H.
name: Zwinderman, Aeilko H.
name: Dupuis, Josée
name: Ziegler, Julie T.
name: Rotimi, Charles N.
name: Fornage, Myriam
name: Dauriz, Marco
name: Goodarzi, Mark O.
name: Tajuddin, Salman M.
name: Raghavan, Sridharan
name: Li, Man
name: Lange, Leslie A.
name: Peyser, Patricia A.
name: Liu, Jingmin
name: Bielak, Lawrence F.
name: Armstrong, Loren L.
name: An, Ping
name: Zhu, Xiaofeng
name: Palmer, Nicholette D.
name: Liu, Ching-Ti
name: Patel, Sanjay R.
name: Lipovich, Leonard
name: Miljkovic, Iva
name: Jhun, Min A.
name: Fu, Yi-Ping
name: Hayes, M. Geoffrey
name: Psaty, Bruce M.
name: Bentley, Amy R.
name: Nayak, Uma
name: Wilson, James G.
name: Johnson, Andrew D.
name: Hivert, Marie-France
name: Karter, Andrew J.
name: Taylor, Kent D.
name: Krauss, Ronald M.
name: Boerwinkle, Eric
name: Agyemang, Charles
name: Liang, Jingling
name: Bowden, Donald W.
name: Edwards, Todd L.
name: Zmuda, Joseph M.
name: Correa, Adolfo
name: Siscovick, David S.
name: Wagenknecht, Lynne E.
name: Kizer, Jorge R.
name: Ferrucci, Luigi
name: Arnett, Donna K.
name: Evans, Michele K.
name: Yanek, Lisa R.
name: Maruthur, Nisa
name: Becker, Diane M.
name: Rybin, Denis V.
name: Ng, Maggie C.Y.
name: Snijder, Marieke B.
name: Chen, Guanjie
name: Adeyemo, Adebowale
name: Nalls, Michael A.
name: Cade, Brian E.
name: Hara, Kazuo
name: Rice, Kenneth M.
name: Sale, Michele M.
name: Kardia, Sharon L.R.
name: Meigs, James B.
name: Patrick, Alan L.
name: Florez, Jose C.
name: Hong, Jaeyoung
name: Zhao, Wei
name: Bottinger, Erwin P.
name: Harris, Tamara B.
name: North, Kari E.
name: Smith, Jennifer A.
name: Kho, Abel N.
name: Rich, Stephen S.
name: Selvin, Elizabeth
name: Cushman, Mary
name: Leong, Aaron
name: Kabagambe, Edmond Kato
name: Drolet, Anne M.
name: Gaulton, Kyle J.
name: Lu, Yingchang
name: Stallings, Sarah C.
name: Yao, Jie
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci