| Literature DB >> 27321945 |
Ching-Ti Liu1, Sridharan Raghavan2, Nisa Maruthur3, Edmond Kato Kabagambe4, Jaeyoung Hong5, Maggie C Y Ng6, Marie-France Hivert7, Yingchang Lu8, Ping An9, Amy R Bentley10, Anne M Drolet11, Kyle J Gaulton12, Xiuqing Guo13, Loren L Armstrong14, Marguerite R Irvin15, Man Li16, Leonard Lipovich17, Denis V Rybin5, Kent D Taylor13, Charles Agyemang18, Nicholette D Palmer19, Brian E Cade20, Wei-Min Chen21, Marco Dauriz22, Joseph A C Delaney23, Todd L Edwards4, Daniel S Evans24, Michele K Evans25, Leslie A Lange26, Aaron Leong27, Jingmin Liu28, Yongmei Liu29, Uma Nayak21, Sanjay R Patel30, Bianca C Porneala27, Laura J Rasmussen-Torvik31, Marieke B Snijder18, Sarah C Stallings32, Toshiko Tanaka33, Lisa R Yanek34, Wei Zhao35, Diane M Becker36, Lawrence F Bielak35, Mary L Biggs37, Erwin P Bottinger38, Donald W Bowden39, Guanjie Chen10, Adolfo Correa40, David J Couper41, Dana C Crawford42, Mary Cushman43, John D Eicher44, Myriam Fornage45, Nora Franceschini46, Yi-Ping Fu47, Mark O Goodarzi48, Omri Gottesman38, Kazuo Hara49, Tamara B Harris50, Richard A Jensen51, Andrew D Johnson52, Min A Jhun35, Andrew J Karter53, Margaux F Keller54, Abel N Kho14, Jorge R Kizer55, Ronald M Krauss56, Carl D Langefeld57, Xiaohui Li13, Jingling Liang58, Simin Liu59, William L Lowe14, Thomas H Mosley60, Kari E North46, Jennifer A Pacheco14, Patricia A Peyser35, Alan L Patrick61, Kenneth M Rice62, Elizabeth Selvin63, Mario Sims40, Jennifer A Smith35, Salman M Tajuddin25, Dhananjay Vaidya64, Mary P Wren65, Jie Yao13, Xiaofeng Zhu58, Julie T Ziegler57, Joseph M Zmuda66, Alan B Zonderman67, Aeilko H Zwinderman18, Adebowale Adeyemo10, Eric Boerwinkle45, Luigi Ferrucci33, M Geoffrey Hayes14, Sharon L R Kardia35, Iva Miljkovic66, James S Pankow68, Charles N Rotimi10, Michele M Sale21, Lynne E Wagenknecht69, Donna K Arnett70, Yii-Der Ida Chen13, Michael A Nalls71, Michael A Province9, W H Linda Kao16, David S Siscovick72, Bruce M Psaty73, James G Wilson74, Ruth J F Loos75, Josée Dupuis76, Stephen S Rich21, Jose C Florez77, Jerome I Rotter13, Andrew P Morris78, James B Meigs79.
Abstract
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.Entities:
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Year: 2016 PMID： 27321945 PMCID： PMC5005440 DOI： 10.1016/j.ajhg.2016.05.006
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.043