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The trans-ancestral genomic architecture of glycemic traits
| File | Description | Size | Format | |
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 The trans-ancestral genomic architecture of glycemic traits.pdf | Accepted version | 5.57 MB | Adobe PDF | View/Open |
| Title: | The trans-ancestral genomic architecture of glycemic traits |
| Authors: | Chen, J Spracklen, CN Marenne, G Varshney, A Corbin, LJ Luan, J Willems, SM Wu, Y Zhang, X Horikoshi, M Boutin, TS Magi, R Waage, J Li-Gao, R Chan, KHK Yao, J Anasanti, MD Chu, AY Claringbould, A Heikkinen, J Hong, J Hottenga, J-J Huo, S Kaakinen, MA Louie, T Maerz, W Moreno-Macias, H Ndungu, A Nelson, SC Nolte, IM North, KE Raulerson, CK Ray, D Rohde, R Rybin, D Schurmann, C Sim, X Southam, L Stewart, ID Wang, CA Wang, Y Wu, P Zhang, W Ahluwalia, TS Appel, EVR Bielak, LF Brody, JA Burtt, NP Cabrera, CP Cade, BE Chai, JF Chai, X Chang, L-C Chen, C-H Chen, BH Chitrala, KN Chiu, Y-F De Haan, HG Delgado, GE Demirkan, A Duan, Q Engmann, J Fatumo, SA Gayan, J Giulianini, F Gong, JH Gustafsson, S Hai, Y Hartwig, FP He, J Heianza, Y Huang, T Huerta-Chagoya, A Hwang, MY Jensen, RA Kawaguchi, T Kentistou, KA Kim, YJ Kleber, ME Kooner, IK Lai, S Lange, LA Langefeld, CD Lauzon, M Li, M Ligthart, S Liu, J Loh, M Long, J Lyssenko, V Mangino, M Marzi, C Montasser, ME Nag, A Nakatochi, M Noce, D Noordam, R Pistis, G Preuss, M Raffield, L Rasmussen-Torvik, LJ Rich, SS Robertson, NR Rueedi, R Ryan, K Sanna, S Saxena, R Schraut, KE Sennblad, B Setoh, K Smith, AV Sparso, T Strawbridge, RJ Takeuchi, F Tan, J Trompet, S Van den Akker, E Van der Most, PJ Verweij, N Vogel, M Wang, H Wang, C Wang, N Warren, HR Wen, W Wilsgaard, T Wong, A Wood, AR Xie, T Zafarmand, MH Zhao, J-H Zhao, W Amin, N Arzumanyan, Z Astrup, A Bakker, SJL Baldassarre, D Beekman, M Bergman, RN Bertoni, A Blueher, M Bonnycastle, LL Bornstein, SR Bowden, DW Cai, Q Campbell, A Campbell, H Chang, YC De Geus, EJC Dehghan, A Du, S Eiriksdottir, G Farmaki, AE Franberg, M Fuchsberger, C Gao, Y Gjesing, AP Goel, A Han, S Hartman, CA Herder, C Hicks, AA Hsieh, C-H Hsueh, WA Ichihara, S Igase, M Ikram, MA Johnson, WC Jorgensen, ME Joshi, PK Kalyani, RR Kandeel, FR Katsuya, T Khor, CC Kiess, W Kolcic, I Kuulasmaa, T Kuusisto, J Lall, K Lam, K Lawlor, DA Lee, NR Lemaitre, RN Li, H Lin, S-Y Lindstrom, J Linneberg, A Liu, J Lorenzo, C Matsubara, T Matsuda, F Mingrone, G Mooijaart, S Moon, S Nabika, T Nadkarni, GN Nadler, JL Nelis, M Neville, MJ Norris, JM Ohyagi, Y Peters, A Peyser, PA Polasek, O Qi, Q Raven, D Reilly, DF Reiner, A Rivideneira, F Roll, K Rudan, I Sabanayagam, C Sandow, K Sattar, N Schuermann, A Shi, J Stringham, HM Taylor, KD Teslovich, TM Thuesen, B Timmers, PRHJ Tremoli, E Tsai, MY Uitterlinden, A Van Dam, RM Van Heemst, D Van Hylckama Vlieg, A Van Vliet-Ostaptchouk, JV Vangipurapu, J Vestergaard, H Wang, T Willems van Dijk, K Zemunik, T Abecasis, GR Adair, LS Aguilar-Salinas, CA Alarcon-Riquelme, ME An, P Aviles-Santa, L Becker, DM Beilin, LJ Bergmann, S Bisgaard, H Black, C Boehnke, M Boerwinkle, E Boehm, BO Bonnelykke, K Boomsma, DI Bottinger, EP Buchanan, TA Canouil, M Caulfield, MJ Chambers, JC Chasman, DI Chen, Y-DI Cheng, C-Y Collins, FS Correa, A Cucca, F De Silva, HJ Dedoussis, G Elmstahl, S Evans, MK Ferrannini, E Ferrucci, L Florez, JC Franks, PW Frayling, TM Froguel, P Gigante, B Goodarzi, MO Gordon-Larsen, P Grallert, H Grarup, N Grimsgaard, S Groop, L Gudnason, V Guo, X Hamsten, A Hansen, T Hayward, C Heckbert, SR Horta, BL Huang, W Ingelsson, E James, PS Jarvelin, M-R Jonas, JB Jukema, JW Kaleebu, P Kaplan, R Kardia, SLR Kato, N Keinanen-Kiukaanniemi, SM Kim, B-J Kivimaki, M Koistinen, HA Kooner, JS Koerner, A Kovacs, P Kuh, D Kumari, M Kutalik, Z Laakso, M Lakka, TA Launer, LJ Leander, K Li, H Lin, X Lind, L Lindgren, C Liu, S Loos, RJF Magnusson, PKE Mahajan, A Metspalu, A Mook-Kanamori, DO Mori, TA Munroe, PB Njolstad, I O'Connell, JR Oldehinkel, AJ Ong, KK Padmanabhan, S Palmer, CNA Palmer, ND Pedersen, O Pennell, CE Porteous, DJ Pramstaller, PP Province, MA Psaty, BM Qi, L Raffel, LJ Rauramaa, R Redline, S Ridker, PM Rosendaal, FR Saaristo, TE Sandhu, M Saramies, J Schneiderman, N Schwarz, P Scott, LJ Selvin, E Sever, P Shu, X-O Slagboom, PE Small, KS Smith, BH Snieder, H Sofer, T Sorensen, TIA Spector, TD Stanton, A Steves, CJ Stumvoll, M Sun, L Tabara, Y Tai, ES Timpson, NJ Tonjes, A Tuomilehto, J Tusie, T Uusitupa, M Van der Harst, P Van Duijn, C Vitart, V Vollenweider, P Vrijkotte, TGM Wagenknecht, LE Walker, M Wang, YX Wareham, NJ Watanabe, RM Watkins, H Wei, WB Wickremasinghe, AR Willemsen, G Wilson, JF Wong, T-Y Wu, J-Y Xiang, AH Yanek, LR Yengo, L Yokota, M Zeggini, E Zheng, W Zonderman, AB Rotter, JI Gloyn, AL McCarthy, MI Dupuis, J Meigs, JB Scott, RA Prokopenko, I Leong, A Liu, C-T Parker, SCJ Mohlke, KL Langenberg, C Wheeler, E Morris, AP Barroso, I |
| Item Type: | Journal Article |
| Abstract: | Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. |
| Issue Date: | 31-May-2021 |
| Date of Acceptance: | 22-Mar-2021 |
| URI: | http://hdl.handle.net/10044/1/98553 |
| DOI: | 10.1038/s41588-021-00852-9 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Research |
| Start Page: | 840 |
| End Page: | 860 |
| Journal / Book Title: | Nature Genetics |
| Volume: | 53 |
| Issue: | 6 |
| Copyright Statement: | © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021. The final publication is available at Springer via https://doi.org/10.1038/s41588-021-00852-9 |
| Sponsor/Funder: | European Commission |
| Funder's Grant Number: | PIEF-GA-2013-626461 |
| Keywords: | Science & Technology Life Sciences & Biomedicine Genetics & Heredity WIDE ASSOCIATION INSULIN-RESISTANCE GENE-EXPRESSION DISEASE RISK VARIANTS GLUCOSE LOCI METAANALYSIS MECHANISMS HEMOGLOBIN Alleles Blood Glucose Epigenesis, Genetic Gene Expression Profiling Genome, Human Genome-Wide Association Study Glycated Hemoglobin A Humans Multifactorial Inheritance Physical Chromosome Mapping Quantitative Trait Loci Quantitative Trait, Heritable Whites Lifelines Cohort Study Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) Humans Blood Glucose Physical Chromosome Mapping Gene Expression Profiling Epigenesis, Genetic Multifactorial Inheritance Quantitative Trait, Heritable Alleles Quantitative Trait Loci Genome, Human Genome-Wide Association Study Glycated Hemoglobin A Whites Science & Technology Life Sciences & Biomedicine Genetics & Heredity WIDE ASSOCIATION INSULIN-RESISTANCE GENE-EXPRESSION DISEASE RISK VARIANTS GLUCOSE LOCI METAANALYSIS MECHANISMS HEMOGLOBIN Developmental Biology 06 Biological Sciences 11 Medical and Health Sciences |
| Publication Status: | Published |
| Online Publication Date: | 2021-05-31 |
| Appears in Collections: | Department of Metabolism, Digestion and Reproduction National Heart and Lung Institute Faculty of Medicine School of Public Health |