Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item The Trans-ancestral genomic architecture of glycemic traits(Nature Pub. Co., 2021) 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, K.H.K; 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, E.V.R.; 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, S.J.L.; 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, E.J.C.; 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.; Lifelines Cohort Study; 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, P.R.H.J.; 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, S.L.R.; 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, R.J.F.; Magnusson, P.K.E.; 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, C.N.A.; 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, T.I.A.; 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, T.G.M.; 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, S.C.J.; Mohlke, K.L.; Langenberg, C.; Wheeler, E.; Morris, A.P.; Barroso, I.; Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) Collaborators.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.Item Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture oftype 2 diabetes susceptibility(Nature Publishing Company, 2014) Mahajan, A.; Go, M.J.; Zhang, W.; Below, J.E.; Gaulton, K.J.; Ferreira, T.; Horikoshi, M.; Johnson, A.D.; Ng, M.C.; Prokopenko, I.; Saleheen, D.; Wang, X.; Zeggini, E.; Abecasis, G.R.; Adair, L.S.; Almgren, P.; Atalay, M.; Aung, T.; Baldassarre, D.; Balkau, B.; Bao, Y.; Barnett, A.H.; Barroso, I.; Basit, A.; Been, L.F.; Beilby, J.; Bell, G.I.; Benediktsson, R.; Bergman, R.N.; Boehm, B.O.; Boerwinkle, E.; Bonnycastle, L.L.; Burtt, N.; Cai, Q.; Campbell, H.; Carey, J.; Cauchi, S.; Caulfield, M.; Chan, J.C.; Chang, L.C.; Chang, T.J.; Chang, Y.C.; Charpentier, G.; Chen, C.H.; Chen, H.; Chen, Y.T.; Chia, K.S.; Chidambaram, M.; Chines, P.S.; Cho, N.H.; Cho, Y.M.; Chuang, L.M.; Collins, F.S.; Cornelis, M.C.; Couper, D.J.; Crenshaw, A.T.; van Dam, R.M.; Danesh, J.; Das, D.; de Faire, U.; Dedoussis, G.; Deloukas, P.; Dimas, A.S.; Dina, C.; Doney, A.S.; Donnelly, P.J.; Dorkhan, M.; van Duijn, C.; Dupuis, J.; Edkins, S.; Elliott, P.; Emilsson, V.; Erbel, R.; Eriksson, J.G.; Escobedo, J.; Esko, T.; Eury, E.; Florez, J.C.; Fontanillas, P.; Forouhi, N.G.; Forsen, T.; Fox, C.; Fraser, R.M.; Frayling, T.M.; Froguel, P.; Frossard, P.; Gao, Y.; Gertow, K.; Gieger, C.; Gigante, B.; Grallert, H.; Grant, G.B.; Grrop, L.C.; Groves, C.J.; Grundberg, E.; Guiducci, C.; Hamsten, A.; Han, B.G.; Hara, K.; Hassanali, N.; Hattersley, A.T.; Hayward, C.; Hedman, A.K.; Herder, C.; Hofman, A.; Holmen, O.L.; Hovingh, K.; Hreidarsson, A.B.; Hu, C.; Hu, F.B.; Hui, J.; Humphries, S.E.; Hunt, S.E.; Hunter, D.J.; Hveem, K.; Hydrie, Z.I.; Ikegami, H.; Illig, T.; Ingelsson, E.; Islam, M.; Isomaa, B.; Jackson, A.U.; Jafar, T.; James, A.; Jia, W.; Jöckel, K.H.; Jonsson, A.; Jowett, J.B.; Kadowaki, T.; Kang, H.M.; Kanoni, S.; Kao, W.H.; Kathiresan, S.; Kato, N.; Katulanda, P.; Keinanen-Kiukaanniemi, K.M.; Kelly, A.M.; Khan, H.; Khaw, K.T.; Khor, C.C.; Kim, H.L.; Kim, S.; Kim, Y.J.; Kinnunen, L.; Klopp, N.; Kong, A.; Korpi-Hyövälti, E.; Kowlessur, S.; Kraft, P.; Kravic, J.; Kristensen, M.M.; Krithika, S.; Kumar, A.; Kumate, J.; Kuusisto, J.; Kwak, S.H.; Laakso, M.; Lagou, V.; Lakka, T.A.; Langenberg, C.; Langford, C.; Lawrence, R.; Leander, K.; Lee, J.M.; Lee, N.R.; Li, M.; Li, X.; Li, Y.; Liang, J.; Liju, S.; Lim, W.Y.; Lind, L.; Lindgren, C.M.; Lindholm, E.; Liu, C.T.; Liu, J.J.; Lobbens, S.; Long, J.; Loos, R.J.; Lu, W.; Luan, J.; Lyssenko, V.; Ma, R.C.; Maeda, S.; Mägi, R.; Männisto, S.; Matthews, D.R.; Meigs, J.B.; Melander, O.; Metspalu, A.; Meyer, J.; Mirza, G.; Mihailov, E.; Moebus, S.; Mohan, V.; Mohlke, K.L.; Morris, A.D.; Mühleisen, T.W.; Müller-Nurasyid, M.; Musk, B.; Nakamura, J.; Nakashima, E.; Navarro, P.; Ng, P.K.; Nica, A.C.; Nilsson, P.M.; Njolstad, I.; Nöthen, M.M.; Ohnaka, K.; Ong, T.H.; Owen, K.R.; Palmer, C.N.; Pankow, J.S.; Park, K.S.; Parkin, M.; Pechlivanis, S.; Pedersen, N.L.; Peltonen, L.; Perry, J.R.; Peters, A.; Pinidiyapathirage, J.M.; Platou, C.G.; Potter, S.; Price, J.F.; Qi, L.; Radha, V.; Rallidis, L.; Rasheed, A.; Rathman, W.; Rauramaa, R.; Raychaudhuri, S.; Rayner, N.W.; Rees, S.D.; Rehnberg, E.; Ripatti, S.; Robertson, N.; Roden, M.; Rossin, E.J.; Rudan, I.; Rybin, D.; Saaristo, T.E.; Salomaa, V.; Saltevo, J.; Samuel, M.; Sanghera, D.K.; Saramies, J.; Scott, J.; Scott, L.J.; Scott, R.A.; Segrè, A.V.; Sehmi, J.; Sennblad, B.; Shah, N.; Shah, S.; Shera, A.S.; Shu, X.O.; Shuldiner, A.R.; Sigurdsson, G.; Sijbrands, E.; Silveira, A.; Sim, X.; Sivapalaratnam, S.; Small, K.S.; So, W.Y.; Stancáková, A.; Stefansson, K.; Steinbach, G.; Steinthorsdottir, V.; Stirrups, K.; Strawbridge, R.J.; Stringham, H.M.; Sun, Q.; Suo, C.; Syvänen, A.C.; Takayanagi, R.; Takeuchi, F.; Tay, W.T.; Teslovich, T.M.; Thorand, B.; Thorleifsson, G.; Thorsteinsdottir, U.; Tikkanen, E.; Trakalo, J.; Tremoli, E.; Trip, M.D.; Tsai, F.J.; Tuomi, T.; Tuomilehto, J.; Uitterlinden, A.G.; Valladares-Salgado, A.; Vedantam, S.; Veglia, F.; Voight, B.F.; Wang, C.; Wareham, N.J.; Wennauer, R.; Wickremasinghe, A.R.; Wilsgaard, T.; Wilson, J.F.; Wiltshire, S.; Winckler, W.; Wong, T.Y.; Wood, A.R.; Wu, J.Y.; Wu, Y.; Yamamoto, K.; Yamauchi, T.; Yang, M.; Yengo, L.; Yokota, M.; Young, R.; Zabaneh, D.; Zhang, F.; Zhang, R.; Zheng., W.; Zimmet, P.Z.; Altshuler, D.; Bowden, D.W.; Cho, Y.S.; Cox, N.J.; Cruz, M.; Hanis, C.L.; Kooner, J.; Lee, J.Y.; Seielstad, M.; Teo, Y.Y.; Boehnke, M.; Parra, E.J.; Chambers, J.C.; Tai, E.S.; McCarthy, M.I.; Morris, A.P.To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.