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Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.
Thursday,2016-08-18 16:07 America/Los_Angeles — zdrager
| Title | Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Liu, C-T, Raghavan, S, Maruthur, N, Kabagambe, EKato, Hong, J, C Y Ng, M, Hivert, M-F, Lu, Y, An, P, Bentley, AR, Drolet, AM, Gaulton, KJ, Guo, X, Armstrong, LL, Irvin, MR, Li, M, Lipovich, L, Rybin, DV, Taylor, KD, Agyemang, C, Palmer, ND, Cade, BE, Chen, W-M, Dauriz, M, Delaney, JAC, Edwards, TL, Evans, DS, Evans, MK, Lange, LA, Leong, A, Liu, J, Liu, Y, Nayak, U, Patel, SR, Porneala, BC, Rasmussen-Torvik, LJ, Snijder, MB, Stallings, SC, Tanaka, T, Yanek, LR, Zhao, W, Becker, DM, Bielak, LF, Biggs, ML, Bottinger, EP, Bowden, DW, Chen, G, Correa, A, Couper, DJ, Crawford, DC, Cushman, M, Eicher, JD, Fornage, M, Franceschini, N, Fu, Y-P, Goodarzi, MO, Gottesman, O, Hara, K, Harris, TB, Jensen, RA, Johnson, AD, Jhun, MA, Karter, AJ, Keller, MF, Kho, AN, Kizer, JR, Krauss, RM, Langefeld, CD, Li, X, Liang, J, Liu, S, Lowe, WL, Mosley, TH, North, KE, Pacheco, JA, Peyser, PA, Patrick, AL, Rice, KM, Selvin, E, Sims, M, Smith, JA, Tajuddin, SM, Vaidya, D, Wren, MP, Yao, J, Zhu, X, Ziegler, JT, Zmuda, JM, Zonderman, AB, Zwinderman, AH, Adeyemo, A, Boerwinkle, E, Ferrucci, L, M Hayes, G, Kardia, SLR, Miljkovic, I, Pankow, JS, Rotimi, CN, Sale, MM, Wagenknecht, LE, Arnett, DK, Chen, Y-DI, Nalls, MA, Province, MA, Kao, LWH, Siscovick, DS, Psaty, BM, Wilson, JG, Loos, RJF, Dupuis, J, Rich, SS, Florez, JC, Rotter, JI, Morris, AP, Meigs, JB |
| Corporate/Institutional Authors | AAAG Consortium, CARe Consortium,, COGENT-BP Consortium, eMERGE Consortium, MEDIA Consortium, MAGIC Consortium, |
| Journal | Am J Hum Genet |
| Volume | 99 |
| Issue | 1 |
| Pagination | 56-75 |
| Date Published | 2016 Jul 7 |
| ISSN | 1537-6605 |
| Abstract | <p>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.</p> |
| DOI | 10.1016/j.ajhg.2016.05.006 |
| Alternate Journal | Am. J. Hum. Genet. |
| PubMed ID | 27321945 |
| PubMed Central ID | PMC5005440 |
| Grant List | K24 DK080140 / DK / NIDDK NIH HHS / United States K24 DK106414 / DK / NIDDK NIH HHS / United States K99 DK081350 / DK / NIDDK NIH HHS / United States M01 RR010284 / RR / NCRR NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States N01 HC095163 / HC / NHLBI NIH HHS / United States N01 HC095166 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R00 DK081350 / DK / NIDDK NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 DK078616 / DK / NIDDK NIH HHS / United States R01 DK089174 / DK / NIDDK NIH HHS / United States R01 HL055673 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States R01 HL060944 / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R21 HL123677 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States U01 HG004603 / HG / NHGRI NIH HHS / United States U01 HG006378 / HG / NHGRI NIH HHS / United States U01 HL054481 / HL / NHLBI NIH HHS / United States UL1 RR025741 / RR / NCRR NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States |