The trans-ancestral genomic architecture of glycemic traits.

Chen, J.; Spracklen, C.N.; Marenne, G.; Varshney, A.; Corbin, L.J.; Luan, J.; Willems, S.M.; Wu, Y.; Zhang, X.; Horikoshi, M.; Boutin, T.S.; Mägi, R.; Waage, J.; Li-Gao, R.; Chan, KHK; Yao, J.; Anasanti, M.D.; Chu, A.Y.; Claringbould, A.; Heikkinen, J.; Hong, J.; Hottenga, J.J.; Huo, S.; Kaakinen, M.A.; Louie, T.; März, W.; Moreno-Macias, H.; Ndungu, A.; Nelson, S.C.; Nolte, I.M.; North, K.E.; Raulerson, C.K.; Ray, D.; Rohde, R.; Rybin, D.; Schurmann, C.; Sim, X.; Southam, L.; Stewart, I.D.; Wang, C.A.; Wang, Y.; Wu, P.; Zhang, W.; Ahluwalia, T.S.; Appel, EVR; Bielak, L.F.; Brody, J.A.; Burtt, N.P.; Cabrera, C.P.; Cade, B.E.; Chai, J.F.; Chai, X.; Chang, L.C.; Chen, C.H.; Chen, B.H.; Chitrala, K.N.; Chiu, Y.F.; de Haan, H.G.; Delgado, G.E.; Demirkan, A.; Duan, Q.; Engmann, J.; Fatumo, S.A.; Gayán, J.; Giulianini, F.; Gong, J.H.; Gustafsson, S.; Hai, Y.; Hartwig, F.P.; He, J.; Heianza, Y.; Huang, T.; Huerta-Chagoya, A.; Hwang, M.Y.; Jensen, R.A.; Kawaguchi, T.; Kentistou, K.A.; Kim, Y.J.; Kleber, M.E.; Kooner, I.K.; Lai, S.; Lange, L.A.; Langefeld, C.D.; Lauzon, M.; Li, M.; Ligthart, S.; Liu, J.; Loh, M.; Long, J.; Lyssenko, V.; Mangino, M.; Marzi, C.; Montasser, M.E.; Nag, A.; Nakatochi, M.; Noce, D.; Noordam, R.; Pistis, G.; Preuss, M.; Raffield, L.; Rasmussen-Torvik, L.J.; Rich, S.S.; Robertson, N.R.; Rueedi, R.; Ryan, K.; Sanna, S.; Saxena, R.; Schraut, K.E.; Sennblad, B.; Setoh, K.; Smith, A.V.; Sparsø, T.; Strawbridge, R.J.; Takeuchi, F.; Tan, J.; Trompet, S.; van den Akker, E.; van der Most, P.J.; Verweij, N.; Vogel, M.; Wang, H.; Wang, C.; Wang, N.; Warren, H.R.; Wen, W.; Wilsgaard, T.; Wong, A.; Wood, A.R.; Xie, T.; Zafarmand, M.H.; Zhao, J.H.; Zhao, W.; Amin, N.; Arzumanyan, Z.; Astrup, A.; Bakker, SJL; Baldassarre, D.; Beekman, M.; Bergman, R.N.; Bertoni, A.; Blüher, M.; Bonnycastle, L.L.; Bornstein, S.R.; Bowden, D.W.; Cai, Q.; Campbell, A.; Campbell, H.; Chang, Y.C.; de Geus, EJC; Dehghan, A.; Du, S.; Eiriksdottir, G.; Farmaki, A.E.; Frånberg, M.; Fuchsberger, C.; Gao, Y.; Gjesing, A.P.; Goel, A.; Han, S.; Hartman, C.A.; Herder, C.; Hicks, A.A.; Hsieh, C.H.; Hsueh, W.A.; Ichihara, S.; Igase, M.; Ikram, M.A.; Johnson, W.C.; Jørgensen, M.E.; Joshi, P.K.; Kalyani, R.R.; Kandeel, F.R.; Katsuya, T.; Khor, C.C.; Kiess, W.; Kolcic, I.; Kuulasmaa, T.; Kuusisto, J.; Läll, K.; Lam, K.; Lawlor, D.A.; Lee, N.R.; Lemaitre, R.N.; Li, H.; Lin, S.Y.; Lindström, J.; Linneberg, A.; Liu, J.; Lorenzo, C.; Matsubara, T.; Matsuda, F.; Mingrone, G.; Mooijaart, S.; Moon, S.; Nabika, T.; Nadkarni, G.N.; Nadler, J.L.; Nelis, M.; Neville, M.J.; Norris, J.M.; Ohyagi, Y.; Peters, A.; Peyser, P.A.; Polasek, O.; Qi, Q.; Raven, D.; Reilly, D.F.; Reiner, A.; Rivideneira, F.; Roll, K.; Rudan, I.; Sabanayagam, C.; Sandow, K.; Sattar, N.; Schürmann, A.; Shi, J.; Stringham, H.M.; Taylor, K.D.; Teslovich, T.M.; Thuesen, B.; Timmers, PRHJ; Tremoli, E.; Tsai, M.Y.; Uitterlinden, A.; van Dam, R.M.; van Heemst, D.; van Hylckama Vlieg, A.; van Vliet-Ostaptchouk, J.V.; Vangipurapu, J.; Vestergaard, H.; Wang, T.; Willems van Dijk, K.; Zemunik, T.; Abecasis, G.R.; Adair, L.S.; Aguilar-Salinas, C.A.; Alarcón-Riquelme, M.E.; An, P.; Aviles-Santa, L.; Becker, D.M.; Beilin, L.J.; Bergmann, S.; Bisgaard, H.; Black, C.; Boehnke, M.; Boerwinkle, E.; Böhm, B.O.; Bønnelykke, K.; Boomsma, D.I.; Bottinger, E.P.; Buchanan, T.A.; Canouil, M.; Caulfield, M.J.; Chambers, J.C.; Chasman, D.I.; Chen, Y.I.; Cheng, C.Y.; Collins, F.S.; Correa, A.; Cucca, F.; de Silva, H.J.; Dedoussis, G.; Elmståhl, S.; Evans, M.K.; Ferrannini, E.; Ferrucci, L.; Florez, J.C.; Franks, P.W.; Frayling, T.M.; Froguel, P.; Gigante, B.; Goodarzi, M.O.; Gordon-Larsen, P.; Grallert, H.; Grarup, N.; Grimsgaard, S.; Groop, L.; Gudnason, V.; Guo, X.; Hamsten, A.; Hansen, T.; Hayward, C.; Heckbert, S.R.; Horta, B.L.; Huang, W.; Ingelsson, E.; James, P.S.; Jarvelin, M.R.; Jonas, J.B.; Jukema, J.W.; Kaleebu, P.; Kaplan, R.; Kardia, SLR; Kato, N.; Keinanen-Kiukaanniemi, S.M.; Kim, B.J.; Kivimaki, M.; Koistinen, H.A.; Kooner, J.S.; Körner, A.; Kovacs, P.; Kuh, D.; Kumari, M.; Kutalik, Z.; Laakso, M.; Lakka, T.A.; Launer, L.J.; Leander, K.; Li, H.; Lin, X.; Lind, L.; Lindgren, C.; Liu, S.; Loos, RJF; Magnusson, PKE; Mahajan, A.; Metspalu, A.; Mook-Kanamori, D.O.; Mori, T.A.; Munroe, P.B.; Njølstad, I.; O'Connell, J.R.; Oldehinkel, A.J.; Ong, K.K.; Padmanabhan, S.; Palmer, CNA; Palmer, N.D.; Pedersen, O.; Pennell, C.E.; Porteous, D.J.; Pramstaller, P.P.; Province, M.A.; Psaty, B.M.; Qi, L.; Raffel, L.J.; Rauramaa, R.; Redline, S.; Ridker, P.M.; Rosendaal, F.R.; Saaristo, T.E.; Sandhu, M.; Saramies, J.; Schneiderman, N.; Schwarz, P.; Scott, L.J.; Selvin, E.; Sever, P.; Shu, X.O.; Slagboom, P.E.; Small, K.S.; Smith, B.H.; Snieder, H.; Sofer, T.; Sørensen, TIA; Spector, T.D.; Stanton, A.; Steves, C.J.; Stumvoll, M.; Sun, L.; Tabara, Y.; Tai, E.S.; Timpson, N.J.; Tönjes, A.; Tuomilehto, J.; Tusie, T.; Uusitupa, M.; van der Harst, P.; van Duijn, C.; Vitart, V.; Vollenweider, P.; Vrijkotte, TGM; Wagenknecht, L.E.; Walker, M.; Wang, Y.X.; Wareham, N.J.; Watanabe, R.M.; Watkins, H.; Wei, W.B.; Wickremasinghe, A.R.; Willemsen, G.; Wilson, J.F.; Wong, T.Y.; Wu, J.Y.; Xiang, A.H.; Yanek, L.R.; Yengo, L.; Yokota, M.; Zeggini, E.; Zheng, W.; Zonderman, A.B.; Rotter, J.I.; Gloyn, A.L.; McCarthy, M.I.; Dupuis, J.; Meigs, J.B.; Scott, R.A.; Prokopenko, I.; Leong, A.; Liu, C.T.; Parker, SCJ; Mohlke, K.L.; Langenberg, C.; Wheeler, E.; Morris, A.P.; Barroso, I.

doi:10.1038/s41588-021-00852-9

The trans-ancestral genomic architecture of glycemic traits.

Details

Download: 34059833_BIB_53C688CA509F.pdf (5574.63 [Ko])
State: Public
Version: Author's accepted manuscript
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Serval ID

serval:BIB_53C688CA509F

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

The trans-ancestral genomic architecture of glycemic traits.

Journal

Nature genetics

Author(s)

Chen J., Spracklen C.N., Marenne G., Varshney A., Corbin L.J., Luan J., Willems S.M., Wu Y., Zhang X., Horikoshi M., Boutin T.S., Mägi R., Waage J., Li-Gao R., Chan KHK, Yao J., Anasanti M.D., Chu A.Y., Claringbould A., Heikkinen J., Hong J., Hottenga J.J., Huo S., Kaakinen M.A., Louie T., März W., Moreno-Macias H., Ndungu A., Nelson S.C., Nolte I.M., North K.E., Raulerson C.K., Ray D., Rohde R., Rybin D., Schurmann C., Sim X., Southam L., Stewart I.D., Wang C.A., Wang Y., Wu P., Zhang W., Ahluwalia T.S., Appel EVR, Bielak L.F., Brody J.A., Burtt N.P., Cabrera C.P., Cade B.E., Chai J.F., Chai X., Chang L.C., Chen C.H., Chen B.H., Chitrala K.N., Chiu Y.F., de Haan H.G., Delgado G.E., Demirkan A., Duan Q., Engmann J., Fatumo S.A., Gayán J., Giulianini F., Gong J.H., Gustafsson S., Hai Y., Hartwig F.P., He J., Heianza Y., Huang T., Huerta-Chagoya A., Hwang M.Y., Jensen R.A., Kawaguchi T., Kentistou K.A., Kim Y.J., Kleber M.E., Kooner I.K., Lai S., Lange L.A., Langefeld C.D., Lauzon M., Li M., Ligthart S., Liu J., Loh M., Long J., Lyssenko V., Mangino M., Marzi C., Montasser M.E., Nag A., Nakatochi M., Noce D., Noordam R., Pistis G., Preuss M., Raffield L., Rasmussen-Torvik L.J., Rich S.S., Robertson N.R., Rueedi R., Ryan K., Sanna S., Saxena R., Schraut K.E., Sennblad B., Setoh K., Smith A.V., Sparsø T., Strawbridge R.J., Takeuchi F., Tan J., Trompet S., van den Akker E., van der Most P.J., Verweij N., Vogel M., Wang H., Wang C., Wang N., Warren H.R., Wen W., Wilsgaard T., Wong A., Wood A.R., Xie T., Zafarmand M.H., Zhao J.H., Zhao W., Amin N., Arzumanyan Z., Astrup A., Bakker SJL, Baldassarre D., Beekman M., Bergman R.N., Bertoni A., Blüher M., Bonnycastle L.L., Bornstein S.R., Bowden D.W., Cai Q., Campbell A., Campbell H., Chang Y.C., de Geus EJC, Dehghan A., Du S., Eiriksdottir G., Farmaki A.E., Frånberg M., Fuchsberger C., Gao Y., Gjesing A.P., Goel A., Han S., Hartman C.A., Herder C., Hicks A.A., Hsieh C.H., Hsueh W.A., Ichihara S., Igase M., Ikram M.A., Johnson W.C., Jørgensen M.E., Joshi P.K., Kalyani R.R., Kandeel F.R., Katsuya T., Khor C.C., Kiess W., Kolcic I., Kuulasmaa T., Kuusisto J., Läll K., Lam K., Lawlor D.A., Lee N.R., Lemaitre R.N., Li H., Lin S.Y., Lindström J., Linneberg A., Liu J., Lorenzo C., Matsubara T., Matsuda F., Mingrone G., Mooijaart S., Moon S., Nabika T., Nadkarni G.N., Nadler J.L., Nelis M., Neville M.J., Norris J.M., Ohyagi Y., Peters A., Peyser P.A., Polasek O., Qi Q., Raven D., Reilly D.F., Reiner A., Rivideneira F., Roll K., Rudan I., Sabanayagam C., Sandow K., Sattar N., Schürmann A., Shi J., Stringham H.M., Taylor K.D., Teslovich T.M., Thuesen B., Timmers PRHJ, Tremoli E., Tsai M.Y., Uitterlinden A., van Dam R.M., van Heemst D., van Hylckama Vlieg A., van Vliet-Ostaptchouk J.V., Vangipurapu J., Vestergaard H., Wang T., Willems van Dijk K., Zemunik T., Abecasis G.R., Adair L.S., Aguilar-Salinas C.A., Alarcón-Riquelme M.E., An P., Aviles-Santa L., Becker D.M., Beilin L.J., Bergmann S., Bisgaard H., Black C., Boehnke M., Boerwinkle E., Böhm B.O., Bønnelykke K., Boomsma D.I., Bottinger E.P., Buchanan T.A., Canouil M., Caulfield M.J., Chambers J.C., Chasman D.I., Chen Y.I., Cheng C.Y., Collins F.S., Correa A., Cucca F., de Silva H.J., Dedoussis G., Elmståhl S., Evans M.K., Ferrannini E., Ferrucci L., Florez J.C., Franks P.W., Frayling T.M., Froguel P., Gigante B., Goodarzi M.O., Gordon-Larsen P., Grallert H., Grarup N., Grimsgaard S., Groop L., Gudnason V., Guo X., Hamsten A., Hansen T., Hayward C., Heckbert S.R., Horta B.L., Huang W., Ingelsson E., James P.S., Jarvelin M.R., Jonas J.B., Jukema J.W., Kaleebu P., Kaplan R., Kardia SLR, Kato N., Keinanen-Kiukaanniemi S.M., Kim B.J., Kivimaki M., Koistinen H.A., Kooner J.S., Körner A., Kovacs P., Kuh D., Kumari M., Kutalik Z., Laakso M., Lakka T.A., Launer L.J., Leander K., Li H., Lin X., Lind L., Lindgren C., Liu S., Loos RJF, Magnusson PKE, Mahajan A., Metspalu A., Mook-Kanamori D.O., Mori T.A., Munroe P.B., Njølstad I., O'Connell J.R., Oldehinkel A.J., Ong K.K., Padmanabhan S., Palmer CNA, Palmer N.D., Pedersen O., Pennell C.E., Porteous D.J., Pramstaller P.P., Province M.A., Psaty B.M., Qi L., Raffel L.J., Rauramaa R., Redline S., Ridker P.M., Rosendaal F.R., Saaristo T.E., Sandhu M., Saramies J., Schneiderman N., Schwarz P., Scott L.J., Selvin E., Sever P., Shu X.O., Slagboom P.E., Small K.S., Smith B.H., Snieder H., Sofer T., Sørensen TIA, Spector T.D., Stanton A., Steves C.J., Stumvoll M., Sun L., Tabara Y., Tai E.S., Timpson N.J., Tönjes A., Tuomilehto J., Tusie T., Uusitupa M., van der Harst P., van Duijn C., Vitart V., Vollenweider P., Vrijkotte TGM, Wagenknecht L.E., Walker M., Wang Y.X., Wareham N.J., Watanabe R.M., Watkins H., Wei W.B., Wickremasinghe A.R., Willemsen G., Wilson J.F., Wong T.Y., Wu J.Y., Xiang A.H., Yanek L.R., Yengo L., Yokota M., Zeggini E., Zheng W., Zonderman A.B., Rotter J.I., Gloyn A.L., McCarthy M.I., Dupuis J., Meigs J.B., Scott R.A., Prokopenko I., Leong A., Liu C.T., Parker SCJ, Mohlke K.L., Langenberg C., Wheeler E., Morris A.P., Barroso I.

Working group(s)

Lifelines Cohort Study, Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC)

Contributor(s)

de Haan H.G., van den Akker E., van der Most P.J., de Geus EJC, van Dam R.M., van Heemst D., van Hylckama Vlieg A., van Willems van Dijk K., de Silva H.J., van der Harst P., van Duijn C.

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

06/2021

Peer-reviewed

Oui

Volume

Number

Pages

840-860

Language

english

Notes

Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

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 <sup>-8</sup> ), 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.

Keywords

Alleles, Blood Glucose/genetics, Epigenesis, Genetic, European Continental Ancestry Group/genetics, Gene Expression Profiling, Genome, Human, Genome-Wide Association Study, Glycated Hemoglobin A/metabolism, Humans, Multifactorial Inheritance/genetics, Physical Chromosome Mapping, Quantitative Trait Loci/genetics, Quantitative Trait, Heritable

URN

urn:nbn:ch:serval-BIB_53C688CA509F9

OAI-PMH

oai:serval.unil.ch:BIB_53C688CA509F

DOI

10.1038/s41588-021-00852-9

Pubmed

34059833

Web of science

000656384400001

Create date

11/06/2021 18:02