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1. Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study

Author: Teslovich, T. M. (Tanya M), Kim, D. S. (Daniel Seung), Yin, X. (Xianyong), Stančáková, A. (Alena), Jackson, A. U. (Anne U.), Wielscher, M. (Matthias), Naj, A. (Adam), Perry, J. R. (John R.B.), Huyghe, J. R. (Jeroen R.), Stringham, H. M. (Heather M.), Davis, J. P. (James P.), Raulerson, C. K. (Chelsea K.), Welch, R. P. (Ryan P.), Fuchsberger, C. (Christian), Locke, A. E. (Adam E.), Sim, X. (Xueling), Chines, P. S. (Peter S.), Narisu, N. (Narisu), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), G. o. (Genetics of Obesity-Related Liver Disease Consortium (GOLD)), T. A. (The Alzheimer’s Disease Genetics Consortium (ADGC)), T. D. (The DIAbetes Genetics Replication And Meta-analysis (DIAGRAM)), Ala-Korpela, M. (Mika), Gudnason, V. (Vilmundur), Musani, S. K. (Solomon K.), Järvelin, M.-R. (Marjo-Riitta), Schellenberg, G. D. (Gerard D.), Speliotes, E. K. (Elizabeth K.), Kuusisto, J. (Johanna), Collins, F. S. (Francis S.), Boehnke, M. (Michael), Laakso, M. (Markku), Mohlke, K. L. (Karen L.), Teslovich, T. M. (Tanya M), Kim, D. S. (Daniel Seung), Yin, X. (Xianyong), Stančáková, A. (Alena), Jackson, A. U. (Anne U.), Wielscher, M. (Matthias), Naj, A. (Adam), Perry, J. R. (John R.B.), Huyghe, J. R. (Jeroen R.), Stringham, H. M. (Heather M.), Davis, J. P. (James P.), Raulerson, C. K. (Chelsea K.), Welch, R. P. (Ryan P.), Fuchsberger, C. (Christian), Locke, A. E. (Adam E.), Sim, X. (Xueling), Chines, P. S. (Peter S.), Narisu, N. (Narisu), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), G. o. (Genetics of Obesity-Related Liver Disease Consortium (GOLD)), T. A. (The Alzheimer’s Disease Genetics Consortium (ADGC)), T. D. (The DIAbetes Genetics Replication And Meta-analysis (DIAGRAM)), Ala-Korpela, M. (Mika), Gudnason, V. (Vilmundur), Musani, S. K. (Solomon K.), Järvelin, M.-R. (Marjo-Riitta), Schellenberg, G. D. (Gerard D.), Speliotes, E. K. (Elizabeth K.), Kuusisto, J. (Johanna), Collins, F. S. (Francis S.), Boehnke, M. (Michael), Laakso, M. (Markku), and Mohlke, K. L. (Karen L.)
Abstract: Comprehensive metabolite profiling captures many highly heritable traits, including amino acid levels, which are potentially sensitive biomarkers for disease pathogenesis. To better understand the contribution of genetic variation to amino acid levels, we performed single variant and gene-based tests of association between nine serum amino acids (alanine, glutamine, glycine, histidine, isoleucine, leucine, phenylalanine, tyrosine, and valine) and 16.6 million genotyped and imputed variants in 8545 non-diabetic Finnish men from the METabolic Syndrome In Men (METSIM) study with replication in Northern Finland Birth Cohort (NFBC1966). We identified five novel loci associated with amino acid levels (P = < 5×10−8): LOC157273/PPP1R3B with glycine (rs9987289, P = 2.3×10−26); ZFHX3 (chr16:73326579, minor allele frequency (MAF) = 0.42%, P = 3.6×10−9), LIPC (rs10468017, P = 1.5×10−8), and WWOX (rs9937914, P = 3.8×10−8) with alanine; and TRIB1 with tyrosine (rs28601761, P = 8×10−9). Gene-based tests identified two novel genes harboring missense variants of MAF < 1% that show aggregate association with amino acid levels: PYCR1 with glycine (Pgene = 1.5×10−6) and BCAT2 with valine (Pgene = 7.4×10−7); neither gene was implicated by single variant association tests. These findings are among the first applications of gene-based tests to identify new loci for amino acid levels. In addition to the seven novel gene associations, we identified five independent signals at established amino acid loci, including two rare variant signals at GLDC (rs138640017, MAF=0.95%, Pconditional = 5.8×10−40) with glycine levels and HAL (rs141635447, MAF = 0.46%, Pconditional = 9.4×10−11) with histidine levels. Examination of all single variant association results in our data revealed a strong inverse relationship between effect size and MAF (Ptrend<0.001). These novel signals provide further insight into the molecular mechanisms of amino acid metabolism and potentially, their perturba
Published: 2018

2. Common, low-frequency, and rare genetic variants associated with lipoprotein subclasses and triglyceride measures in Finnish men from the METSIM study

Author: Davis, J. P. (James P.), Huyghe, J. R. (Jeroen R.), Locke, A. E. (Adam E.), Jackson, A. U. (Anne U.), Sim, X. (Xueling), Stringham, H. M. (Heather M.), Teslovich, T. M. (Tanya M.), Welch, R. P. (Ryan P.), Fuchsberger, C. (Christian), Narisu, N. (Narisu), Chines, P. S. (Peter S.), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), Ala-Korpela, M. (Mika), Kuusisto, J. (Johanna), Collins, F. S. (Francis S.), Laakso, M. (Markku), Boehnke, M. (Michael), and Mohlke, K. L. (Karen L.)
Abstract: Lipid and lipoprotein subclasses are associated with metabolic and cardiovascular diseases, yet the genetic contributions to variability in subclass traits are not fully understood. We conducted single-variant and gene-based association tests between 15.1M variants from genome-wide and exome array and imputed genotypes and 72 lipid and lipoprotein traits in 8,372 Finns. After accounting for 885 variants at 157 previously identified lipid loci, we identified five novel signals near established loci at HIF3A, ADAMTS3, PLTP, LCAT, and LIPG. Four of the signals were identified with a low-frequency (0.005
Published: 2017

3. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, A.E. (Anne), Winkler, T.W. (Thomas W.), Feitosa, M.F., Graff, M.J. (Maud J.L.), Fisher, V.A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J.S. (Julius S.), Ahluwalia, T.S. (Tarunveer Singh), Chu, A.Y. (Audrey Y), Heard-Costa, N.L. (Nancy), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J.D. (John D.), Kutalik, Z. (Zoltán), Xue, L. (Luting), Mahajan, A. (Anubha), Renström, F. (Frida), Wu, J.M.W. (Joseph M. W.), Qi, Q., Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L.F. (Lawrence F.), Bonnefond, A. (Amélie), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M.N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Justesen, J.M. (Johanne M.), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M.E. (Marcus), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J., Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R.P.S. (Rita), Müller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A.V. (Albert), Smith, J.A. (Jennifer A), Stanča'kova, A. (Alena), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather M.), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vedantam, S. (Sailaja), Verweij, N. (Niek), Vink, J.M. (Jacqueline), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zimmermann, M.E. (Martina E.), Zubair, N. (Niha), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S.J.L. (Stephan), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin), Braga, D. (Daniele), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Campbell, H. (Harry), Chambers, J.C. (John C.), Collins, F.S. (Francis), Curran, J.E. (Joanne), Borst, G.J. (Gert) de, Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Delgado, G., Ruijter, H.M. (Hester ) den, Eiriksdottir, G. (Gudny), Eriksson, A.L. (Anna L.), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T.B. (Tanja), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Göran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T.B. (Tamara), Hartman, C.A. (C.), Hassinen, M. (Maija), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J., Hollensted, M. (Mette), Holmen, O.L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. (Alan), Jansson, J.-O. (John-Olov), Jarvelin, M.-R. (Marjo-Riitta), Jhun, M.A. (Min A.), Jørgensen, M.E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Krämer, B.K. (Bernhard), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Leander, K. (Karin), Lee, N.R. (Nanette R.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stéphane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G.H. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P.A. (Pamela), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N.G. (Nicholas), McKenzie, C.A. (Colin), McKnight, B. (Barbara), Mellström, D. (Dan), Menni, C. (Cristina), Montgomery, G.W. (Grant W.), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P.A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D.J. (David J.), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C. (D. C.), Rasmussen-Torvik, L.J. (Laura), Rawal, R. (Rajesh), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Rose, L.M. (Lynda M.), Bien, S.A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R.A. (Robert), Sennblad, B. (Bengt), Siemelink, M.A. (Marten A.), Silbernagel, G. (Günther), Slagboom, P.E. (Eline), Snieder, H. (Harold), Staessen, J.A. (Jan A.), Stott, D.J. (David. J.), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Taylor, K.D. (Kent), Tayo, B. (Bamidele), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Völzke, H. (Henry), Vonk, J.M. (Judith), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Westendorp, R.G.J. (Rudi), Wild, S.H. (Sarah), Willemsen, G., Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zhao, W. (Wei), Zillikens, M.C. (Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Böger, C.A. (Carsten), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Bruinenberg, M. (M.), Chasman, D.I. (Daniel), Ida Chen, Y.-D. (Yii-Der), Chines, P.S. (Peter), Cooper, R.S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), Faire, U. (Ulf) de, Ferrucci, L. (Luigi), Franks, P.W. (Paul), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.J. (Hans Jörgen), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A.D. (Andrew D.), Jukema, J.W. (Jan Wouter), Kardia, S.L.R. (Sharon), Kivimaki, M. (Mika), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), März, W. (Winfried), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Morris, A.P. (Andrew), Ohlsson, C. (Claes), Palmer, L.J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B.H. (Blair), Sørensen, T.I.A. (Thorkild), Strauch, K. (Konstantin), Tiemeier, H.W. (Henning), Tremoli, E. (Elena), Van Der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Weir, D.R. (David), Whitfield, J. (John), Wilson, J.F. (James F.), Tyrrell, A.W.R., Frayling, T.M. (Timothy M.), Barroso, I.E. (Inês), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Hirschhorn, J.N. (Joel), Hunter, D.J. (David J.), Spector, T.D. (Timothy), Strachan, D.P. (David), Duijn, C.M. (Cornelia) van, Heid, I.M. (Iris), Mohlke, K.L. (Karen), Marchini, J. (Jonathan), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Liu, C.-T. (Ching-Ti), Borecki, I.B. (Ingrid), North, K.E. (Kari), Cupples, L.A. (Adrienne), Justice, A.E. (Anne), Winkler, T.W. (Thomas W.), Feitosa, M.F., Graff, M.J. (Maud J.L.), Fisher, V.A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J.S. (Julius S.), Ahluwalia, T.S. (Tarunveer Singh), Chu, A.Y. (Audrey Y), Heard-Costa, N.L. (Nancy), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J.D. (John D.), Kutalik, Z. (Zoltán), Xue, L. (Luting), Mahajan, A. (Anubha), Renström, F. (Frida), Wu, J.M.W. (Joseph M. W.), Qi, Q., Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L.F. (Lawrence F.), Bonnefond, A. (Amélie), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M.N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Justesen, J.M. (Johanne M.), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M.E. (Marcus), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J., Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R.P.S. (Rita), Müller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A.V. (Albert), Smith, J.A. (Jennifer A), Stanča'kova, A. (Alena), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather M.), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vedantam, S. (Sailaja), Verweij, N. (Niek), Vink, J.M. (Jacqueline), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zimmermann, M.E. (Martina E.), Zubair, N. (Niha), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S.J.L. (Stephan), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin), Braga, D. (Daniele), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Campbell, H. (Harry), Chambers, J.C. (John C.), Collins, F.S. (Francis), Curran, J.E. (Joanne), Borst, G.J. (Gert) de, Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Delgado, G., Ruijter, H.M. (Hester ) den, Eiriksdottir, G. (Gudny), Eriksson, A.L. (Anna L.), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T.B. (Tanja), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Göran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T.B. (Tamara), Hartman, C.A. (C.), Hassinen, M. (Maija), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J., Hollensted, M. (Mette), Holmen, O.L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. (Alan), Jansson, J.-O. (John-Olov), Jarvelin, M.-R. (Marjo-Riitta), Jhun, M.A. (Min A.), Jørgensen, M.E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Krämer, B.K. (Bernhard), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Leander, K. (Karin), Lee, N.R. (Nanette R.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stéphane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G.H. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P.A. (Pamela), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N.G. (Nicholas), McKenzie, C.A. (Colin), McKnight, B. (Barbara), Mellström, D. (Dan), Menni, C. (Cristina), Montgomery, G.W. (Grant W.), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P.A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D.J. (David J.), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C. (D. C.), Rasmussen-Torvik, L.J. (Laura), Rawal, R. (Rajesh), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Rose, L.M. (Lynda M.), Bien, S.A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R.A. (Robert), Sennblad, B. (Bengt), Siemelink, M.A. (Marten A.), Silbernagel, G. (Günther), Slagboom, P.E. (Eline), Snieder, H. (Harold), Staessen, J.A. (Jan A.), Stott, D.J. (David. J.), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Taylor, K.D. (Kent), Tayo, B. (Bamidele), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Völzke, H. (Henry), Vonk, J.M. (Judith), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Westendorp, R.G.J. (Rudi), Wild, S.H. (Sarah), Willemsen, G., Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zhao, W. (Wei), Zillikens, M.C. (Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Böger, C.A. (Carsten), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Bruinenberg, M. (M.), Chasman, D.I. (Daniel), Ida Chen, Y.-D. (Yii-Der), Chines, P.S. (Peter), Cooper, R.S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), Faire, U. (Ulf) de, Ferrucci, L. (Luigi), Franks, P.W. (Paul), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.J. (Hans Jörgen), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A.D. (Andrew D.), Jukema, J.W. (Jan Wouter), Kardia, S.L.R. (Sharon), Kivimaki, M. (Mika), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), März, W. (Winfried), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Morris, A.P. (Andrew), Ohlsson, C. (Claes), Palmer, L.J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B.H. (Blair), Sørensen, T.I.A. (Thorkild), Strauch, K. (Konstantin), Tiemeier, H.W. (Henning), Tremoli, E. (Elena), Van Der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Weir, D.R. (David), Whitfield, J. (John), Wilson, J.F. (James F.), Tyrrell, A.W.R., Frayling, T.M. (Timothy M.), Barroso, I.E. (Inês), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Hirschhorn, J.N. (Joel), Hunter, D.J. (David J.), Spector, T.D. (Timothy), Strachan, D.P. (David), Duijn, C.M. (Cornelia) van, Heid, I.M. (Iris), Mohlke, K.L. (Karen), Marchini, J. (Jonathan), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Liu, C.-T. (Ching-Ti), Borecki, I.B. (Ingrid), North, K.E. (Kari), and Cupples, L.A. (Adrienne)
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting
Published: 2017
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4. Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

Author: Graff, M.J. (Maud J.L.), Scott, R.A. (Robert), Justice, A.E. (Anne), Young, K.L. (Kristin L.), Feitosa, M.F. (Mary Furlan), Barata, L. (Llilda), Winkler, T.W. (Thomas W.), Chu, A.Y. (Audrey), Mahajan, A. (Anubha), Hadley, D. (David), Xue, L. (Luting), Workalemahu, T. (Tsegaselassie), Heard-Costa, N.L. (Nancy), Hoed, M. (Marcel) den, Ahluwalia, T.S. (Tarunveer Singh), Qi, Q., Ngwa, J.S., Renström, F. (Frida), Quaye, L. (Lydia), Eicher, J.D. (John D.), Hayes, J.E. (James E.), Cornelis, M. (Marilyn), Kutalik, Z. (Zoltán), Lim, E. (Elise), Luan, J. (Jian'An), Huffman, J.E. (Jennifer), Zhang, W. (Weihua), Zhao, W. (Wei), Griffin, P.J. (Paula J.), Haller, T. (Toomas), Ahmad, S. (Shafqat), Marques-Vidal, P. (Pedro), Bien, S. (Stephanie), Yengo, L. (Loic), Teumer, A. (Alexander), Smith, A.V. (Albert Vernon), Kumari, M. (Meena), Harder, M.N. (Marie Neergaard), Justesen, J.M. (Johanne M.), Kleber, M.E. (Marcus), Hollensted, M. (Mette), Lohman, K. (Kurt), Rivera, N.V. (Natalia), Whitfield, J.B. (John B.), Zhao, J.H. (Jing Hua), Stringham, H.M. (Heather), Lyytikäinen, L.-P. (Leo-Pekka), Huppertz, C. (Charlotte), Willemsen, G.A.H.M. (Gonneke), Peyrot, W.J. (Wouter ), Wu, Y. (Ying), Kristiansson, K. (Kati), Demirkan, A. (Ayşe), Fornage, M. (Myriam), Hassinen, M. (Maija), Bielak, L.F. (Lawrence F.), Cadby, G. (Gemma), Tanaka, T. (Toshiko), Mägi, R. (Reedik), Most, P.J. (Peter) van der, Jackson, A.U. (Anne), Bragg-Gresham, J.L. (Jennifer L.), Vitart, V. (Veronique), Marten, J. (Jonathan), Navarro, P. (Pau), Bellis, C. (Claire), Pasko, D. (Dorota), Johansson, Å. (Åsa), Snitker, S. (Soren), Cheng, Y.-C. (Yu-Ching), Eriksson, J. (Joel), Lim, U. (Unhee), Aadahl, M. (Mette), Adair, L.S. (Linda), Amin, N. (Najaf), Balkau, B. (Beverley), Auvinen, J. (Juha), Beilby, J.P. (John), Bergman, R.N. (Richard N.), Bergmann, S.M. (Sven), Bertoni, A.G. (Alain G.), Blangero, J. (John), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borja, J.B. (Judith), Brage, S. (Soren), Busonero, F., Buyske, S. (Steven), Campbell, H. (Harry), Chines, P.S. (Peter), Collins, F.S. (Francis), Corre, T. (Tanguy), Smith, G.D. (George Davey), Delgado, G., Dueker, N. (Nicole), Dörr, M. (Marcus), Ebeling, T. (Tapani), Eiriksdottir, G. (Gudny), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Fu, M. (Mao), Færch, K. (Kristine), Gieger, C. (Christian), Gläser, S., Gong, J. (Jian), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grammer, T.B. (Tanja B), Grarup, N. (Niels), Grootheest, G. (Gerard) van, Harald, K. (Kennet), Hastie, N. (Nick), Havulinna, A.S. (Aki), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J. (Lynne), Holmens, O.L. (Oddgeir L.), Holzapfel, C. (Christina), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huang, T. (Tao), Hui, J. (Jennie), Huth, C. (Cornelia), Hutri-Kähönen, N. (Nina), James, A. (Alan), Jansson, J.-O. (John-Olov), Jhun, M.A. (Min A.), Juonala, M. (Markus), Kinnunen, L. (Leena), Koistinen, H. (Heikki), Kolcic, I. (Ivana), Komulainen, P. (Pirjo), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Kähönen, M. (Mika), Lakka, T.A. (Timo), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lindgren, C.M. (Cecilia M.), Lorentzon, M. (Mattias), Luben, R.N. (Robert), Marre, M. (Michel), Milaneschi, Y. (Yuri), Monda, K.L. (Keri), Montgomery, G.W. (Grant W.), Moor, M.H.M. de, Mulas, A. (Antonella), Müller-Nurasyid, M. (Martina), Musk, A.W., Männikkö, R. (Reija), Männistö, S. (Satu), Narisu, N. (Narisu), Nauck, M. (Matthias), Nettleton, J.A. (Jennifer ), Nolte, I.M. (Ilja M.), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Paternoster, L. (Lavinia), Perez, J. (Jeremiah), Perola, M. (Markus), Peters, A. (Annette), Peters, U. (Ulrike), Peyser, P.A. (Patricia A.), Prokopenko, I. (Inga), Puolijoki, H. (Hannu), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rasmussen-Torvik, L.J. (Laura J.), Rawal, R. (Rajesh), Ridker, P.M. (Paul), Rose, L.M. (Lynda), Rudan, I. (Igor), Sarti, C. (Cinzia), Sarzynski, M.A. (Mark A.), Savonen, K. (Kai), Scott, W.R. (William R.), Sanna, S. (Serena), Shuldiner, A.R. (Alan), Sidney, S. (Steve), Silbernagel, G. (Günther), Smith, B.H., Smith, J.A. (Jennifer A), Snieder, H. (Harold), Stancáková, A. (Alena), Sternfeld, B. (Barbara), Swift, A.J. (Amy), Tammelin, T. (Tuija), Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Vandenput, L. (Liesbeth), Vestergaard, H. (Henrik), Vliet-Ostaptchouk, J.V. (Jana) van, Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Waeber, G. (Gérard), Walker, M. (Mark), Wild, S. (Sarah), Wong, A. (Andrew), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Zubair, N. (Niha), Haiman, C.A. (Christopher), LeMarchand, L. (Loic), Gyllensten, U. (Ulf), Ohlsson, C. (Claes), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Perusse, L. (Louis), Wilson, J.F. (James), Hayward, C. (Caroline), Polasek, O. (Ozren), Cucca, F. (Francesco), Hveem, K. (Kristian), Hartman, C.A. (Catharina A.), Tönjes, A. (Anke), Bandinelli, S. (Stefania), Palmer, L.J. (Lyle J.), Kardia, S.L.R. (Sharon L. R.), Rauramaa, R. (Rainer), Sørensen, T.I.A. (Thorkild), Tuomilehto, J. (Jaakko), Salomaa, V. (Veikko), Penninx, B.W.J.H. (Brenda), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Lehtimäki, T. (Terho), Mangino, M. (Massimo), Laakso, M. (Markku), Bouchard, C. (Claude), Martin, N.G. (Nicholas), Kuh, D. (Diana), Liu, Y. (YongMei), Linneberg, A. (Allan), März, W. (Winfried), Strauch, K. (Konstantin), Kivimaki, M. (Mika), Harris, T.B. (Tamara), Gudnason, V. (Vilmundur), Völzke, H. (Henry), Qi, L. (Lu), Jarvelin, M.-R. (Marjo-Riitta), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Froguel, P. (Philippe), Kooperberg, C. (Charles), Vollenweider, P. (Peter), Hallmans, G. (Göran), Hansen, T. (T.), Pedersen, O. (Oluf), Metspalu, A. (Andres), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Weir, D.R. (David), Porteous, D.J. (David J.), Boerwinkle, E.A. (Eric), Chasman, D.I. (Daniel), Abecasis, G.R. (Gonçalo R.), Barroso, I.E. (Inês), McCarthy, M.I. (Mark I.), Frayling, T.M. (Timothy), O’Connell, J.R. (Jeffrey R.), Duijn, C.M. (Cornelia) van, Boehnke, M. (Michael), Heid, I.M. (Iris), Mohlke, K.L. (Karen), Strachan, D.P. (David), Fox, C.S. (Caroline), Liu, C.-T. (Ching-Ti), Hirschhorn, J.N. (Joel), Klein, R.J. (Robert J.), Johnson, A.D. (Andrew), Borecki, I.B. (Ingrid), Franks, P.W. (Paul), North, K.E. (Kari), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Graff, M.J. (Maud J.L.), Scott, R.A. (Robert), Justice, A.E. (Anne), Young, K.L. (Kristin L.), Feitosa, M.F. (Mary Furlan), Barata, L. (Llilda), Winkler, T.W. (Thomas W.), Chu, A.Y. (Audrey), Mahajan, A. (Anubha), Hadley, D. (David), Xue, L. (Luting), Workalemahu, T. (Tsegaselassie), Heard-Costa, N.L. (Nancy), Hoed, M. (Marcel) den, Ahluwalia, T.S. (Tarunveer Singh), Qi, Q., Ngwa, J.S., Renström, F. (Frida), Quaye, L. (Lydia), Eicher, J.D. (John D.), Hayes, J.E. (James E.), Cornelis, M. (Marilyn), Kutalik, Z. (Zoltán), Lim, E. (Elise), Luan, J. (Jian'An), Huffman, J.E. (Jennifer), Zhang, W. (Weihua), Zhao, W. (Wei), Griffin, P.J. (Paula J.), Haller, T. (Toomas), Ahmad, S. (Shafqat), Marques-Vidal, P. (Pedro), Bien, S. (Stephanie), Yengo, L. (Loic), Teumer, A. (Alexander), Smith, A.V. (Albert Vernon), Kumari, M. (Meena), Harder, M.N. (Marie Neergaard), Justesen, J.M. (Johanne M.), Kleber, M.E. (Marcus), Hollensted, M. (Mette), Lohman, K. (Kurt), Rivera, N.V. (Natalia), Whitfield, J.B. (John B.), Zhao, J.H. (Jing Hua), Stringham, H.M. (Heather), Lyytikäinen, L.-P. (Leo-Pekka), Huppertz, C. (Charlotte), Willemsen, G.A.H.M. (Gonneke), Peyrot, W.J. (Wouter ), Wu, Y. (Ying), Kristiansson, K. (Kati), Demirkan, A. (Ayşe), Fornage, M. (Myriam), Hassinen, M. (Maija), Bielak, L.F. (Lawrence F.), Cadby, G. (Gemma), Tanaka, T. (Toshiko), Mägi, R. (Reedik), Most, P.J. (Peter) van der, Jackson, A.U. (Anne), Bragg-Gresham, J.L. (Jennifer L.), Vitart, V. (Veronique), Marten, J. (Jonathan), Navarro, P. (Pau), Bellis, C. (Claire), Pasko, D. (Dorota), Johansson, Å. (Åsa), Snitker, S. (Soren), Cheng, Y.-C. (Yu-Ching), Eriksson, J. (Joel), Lim, U. (Unhee), Aadahl, M. (Mette), Adair, L.S. (Linda), Amin, N. (Najaf), Balkau, B. (Beverley), Auvinen, J. (Juha), Beilby, J.P. (John), Bergman, R.N. (Richard N.), Bergmann, S.M. (Sven), Bertoni, A.G. (Alain G.), Blangero, J. (John), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borja, J.B. (Judith), Brage, S. (Soren), Busonero, F., Buyske, S. (Steven), Campbell, H. (Harry), Chines, P.S. (Peter), Collins, F.S. (Francis), Corre, T. (Tanguy), Smith, G.D. (George Davey), Delgado, G., Dueker, N. (Nicole), Dörr, M. (Marcus), Ebeling, T. (Tapani), Eiriksdottir, G. (Gudny), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Fu, M. (Mao), Færch, K. (Kristine), Gieger, C. (Christian), Gläser, S., Gong, J. (Jian), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grammer, T.B. (Tanja B), Grarup, N. (Niels), Grootheest, G. (Gerard) van, Harald, K. (Kennet), Hastie, N. (Nick), Havulinna, A.S. (Aki), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J. (Lynne), Holmens, O.L. (Oddgeir L.), Holzapfel, C. (Christina), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huang, T. (Tao), Hui, J. (Jennie), Huth, C. (Cornelia), Hutri-Kähönen, N. (Nina), James, A. (Alan), Jansson, J.-O. (John-Olov), Jhun, M.A. (Min A.), Juonala, M. (Markus), Kinnunen, L. (Leena), Koistinen, H. (Heikki), Kolcic, I. (Ivana), Komulainen, P. (Pirjo), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Kähönen, M. (Mika), Lakka, T.A. (Timo), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lindgren, C.M. (Cecilia M.), Lorentzon, M. (Mattias), Luben, R.N. (Robert), Marre, M. (Michel), Milaneschi, Y. (Yuri), Monda, K.L. (Keri), Montgomery, G.W. (Grant W.), Moor, M.H.M. de, Mulas, A. (Antonella), Müller-Nurasyid, M. (Martina), Musk, A.W., Männikkö, R. (Reija), Männistö, S. (Satu), Narisu, N. (Narisu), Nauck, M. (Matthias), Nettleton, J.A. (Jennifer ), Nolte, I.M. (Ilja M.), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Paternoster, L. (Lavinia), Perez, J. (Jeremiah), Perola, M. (Markus), Peters, A. (Annette), Peters, U. (Ulrike), Peyser, P.A. (Patricia A.), Prokopenko, I. (Inga), Puolijoki, H. (Hannu), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rasmussen-Torvik, L.J. (Laura J.), Rawal, R. (Rajesh), Ridker, P.M. (Paul), Rose, L.M. (Lynda), Rudan, I. (Igor), Sarti, C. (Cinzia), Sarzynski, M.A. (Mark A.), Savonen, K. (Kai), Scott, W.R. (William R.), Sanna, S. (Serena), Shuldiner, A.R. (Alan), Sidney, S. (Steve), Silbernagel, G. (Günther), Smith, B.H., Smith, J.A. (Jennifer A), Snieder, H. (Harold), Stancáková, A. (Alena), Sternfeld, B. (Barbara), Swift, A.J. (Amy), Tammelin, T. (Tuija), Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Vandenput, L. (Liesbeth), Vestergaard, H. (Henrik), Vliet-Ostaptchouk, J.V. (Jana) van, Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Waeber, G. (Gérard), Walker, M. (Mark), Wild, S. (Sarah), Wong, A. (Andrew), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Zubair, N. (Niha), Haiman, C.A. (Christopher), LeMarchand, L. (Loic), Gyllensten, U. (Ulf), Ohlsson, C. (Claes), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Perusse, L. (Louis), Wilson, J.F. (James), Hayward, C. (Caroline), Polasek, O. (Ozren), Cucca, F. (Francesco), Hveem, K. (Kristian), Hartman, C.A. (Catharina A.), Tönjes, A. (Anke), Bandinelli, S. (Stefania), Palmer, L.J. (Lyle J.), Kardia, S.L.R. (Sharon L. R.), Rauramaa, R. (Rainer), Sørensen, T.I.A. (Thorkild), Tuomilehto, J. (Jaakko), Salomaa, V. (Veikko), Penninx, B.W.J.H. (Brenda), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Lehtimäki, T. (Terho), Mangino, M. (Massimo), Laakso, M. (Markku), Bouchard, C. (Claude), Martin, N.G. (Nicholas), Kuh, D. (Diana), Liu, Y. (YongMei), Linneberg, A. (Allan), März, W. (Winfried), Strauch, K. (Konstantin), Kivimaki, M. (Mika), Harris, T.B. (Tamara), Gudnason, V. (Vilmundur), Völzke, H. (Henry), Qi, L. (Lu), Jarvelin, M.-R. (Marjo-Riitta), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Froguel, P. (Philippe), Kooperberg, C. (Charles), Vollenweider, P. (Peter), Hallmans, G. (Göran), Hansen, T. (T.), Pedersen, O. (Oluf), Metspalu, A. (Andres), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Weir, D.R. (David), Porteous, D.J. (David J.), Boerwinkle, E.A. (Eric), Chasman, D.I. (Daniel), Abecasis, G.R. (Gonçalo R.), Barroso, I.E. (Inês), McCarthy, M.I. (Mark I.), Frayling, T.M. (Timothy), O’Connell, J.R. (Jeffrey R.), Duijn, C.M. (Cornelia) van, Boehnke, M. (Michael), Heid, I.M. (Iris), Mohlke, K.L. (Karen), Strachan, D.P. (David), Fox, C.S. (Caroline), Liu, C.-T. (Ching-Ti), Hirschhorn, J.N. (Joel), Klein, R.J. (Robert J.), Johnson, A.D. (Andrew), Borecki, I.B. (Ingrid), Franks, P.W. (Paul), North, K.E. (Kari), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), and Kilpeläinen, T.O. (Tuomas)
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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5. Genome-wide physical activity interactions in adiposity:a meta-analysis of 200,452 adults

Author: Graff, M. (Mariaelisa), Scott, R. A. (Robert A.), Justice, A. E. (Anne E.), Young, K. L. (Kristin L.), Feitosa, M. F. (Mary F.), Barata, L. (Llilda), Winkler, T. W. (Thomas W.), Chu, A. Y. (Audrey Y.), Mahajan, A. (Anubha), Hadley, D. (David), Xue, L. (Luting), Workalemahu, T. (Tsegaselassie), Heard-Costa, N. L. (Nancy L.), den Hoed, M. (Marcel), Ahluwalia, T. S. (Tarunveer S.), Qi, Q. (Qibin), Ngwa, J. S. (Julius S.), Renstrom, F. (Frida), Quaye, L. (Lydia), Eicher, J. D. (John D.), Hayes, J. E. (James E.), Cornelis, M. (Marilyn), Kutalik, Z. (Zoltan), Lim, E. (Elise), Luan, J. (Jian'an), Huffman, J. E. (Jennifer E.), Zhang, W. (Weihua), Zhao, W. (Wei), Griffin, P. J. (Paula J.), Haller, T. (Toomas), Ahmad, S. (Shafqat), Marques-Vidal, P. M. (Pedro M.), Bien, S. (Stephanie), Yengo, L. (Loic), Teumer, A. (Alexander), Smith, A. V. (Albert Vernon), Kumari, M. (Meena), Harder, M. N. (Marie Neergaard), Justesen, J. M. (Johanne Marie), Kleber, M. E. (Marcus E.), Hollensted, M. (Mette), Lohman, K. (Kurt), Rivera, N. V. (Natalia V.), Whitfield, J. B. (John B.), Zhao, J. H. (Jing Hua), Stringham, H. M. (Heather M.), Lyytikainen, L.-P. (Leo-Pekka), Huppertz, C. (Charlotte), Willemsen, G. (Gonneke), Peyrot, W. J. (Wouter J.), Wu, Y. (Ying), Kristiansson, K. (Kati), Demirkan, A. (Ayse), Fornage, M. (Myriam), Hassinen, M. (Maija), Bielak, L. F. (Lawrence F.), Cadby, G. (Gemma), Tanaka, T. (Toshiko), Magl, R. (Reedlk), Van der Most, P. J. (Peter J.), Jackson, A. U. (Anne U.), Bragg-Gresham, J. L. (Jennifer L.), Vitart, V. (Veronique), Marten, J. (Jonathan), Navarro, P. (Pau), Bellis, C. (Claire), Pasko, D. (Dorota), Johansson, A. (Asa), Snitker, S. (Soren), Cheng, Y.-C. (Yu-Ching), Eriksson, J. (Joel), Lim, U. (Unhee), Aadahl, M. (Mette), Adair, L. S. (Linda S.), Amin, N. (Najaf), Balkau, B. (Beverley), Auvinen, J. (Juha), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Bertoni, A. G. (Alain G.), Blangero, J. (John), Bonnefond, A. (Amelle), Bonnycastle, L. L. (Lori L.), Borja, J. B. (Judith B.), Brage, S. (Soren), Busonero, F. (Fabio), Buyske, S. (Steve), Campbell, H. (Harry), Chines, P. S. (Peter S.), Collins, F. S. (Francis S.), Corre, T. (Tanguy), Smith, G. D. (George Davey), Delgado, G. E. (Graciela E.), Dueker, N. (Nicole), Doerr, M. (Marcus), Ebeling, T. (Tapani), Eiriksdottir, G. (Gudny), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Fu, M. (Mao), Faerch, K. (Kristine), Gieger, C. (Christian), Glaeser, S. (Sven), Gong, J. (Jian), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), van Grootheest, G. (Gerard), Harald, K. (Kennet), Hastie, N. D. (Nicholas D.), Havulinna, A. S. (Aki S.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Holmens, O. L. (Oddgeir L.), Holzapfel, C. (Christina), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Huang, T. (Tao), Hui, J. (Jennie), Huth, C. (Cornelia), Hutri-Kahonen, N. (Nina), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Jhun, M. A. (Min A.), Juonala, M. (Markus), Kinnunen, L. (Leena), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Komulainen, P. (Pirjo), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Kahonen, M. (Mika), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Lehne, B. (Benjamin), Lindgren, C. M. (Cecilia M.), Lorentzon, M. (Mattias), Luben, R. (Robert), Marre, M. (Michel), Milaneschi, Y. (Yuri), Monda, K. L. (Keri L.), Montgomery, G. W. (Grant W.), De Moor, M. H. (Marleen H. M.), Mulas, A. (Antonella), Mueller-Nurasyid, M. (Martina), Musk, A. W. (A. W.), Mannikko, R. (Reija), Mannisto, S. (Satu), Narisu, N. (Narisu), Nauck, M. (Matthias), Nettleton, J. A. (Jennifer A.), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Paternoster, L. (Lavinia), Perez, J. (Jeremiah), Perola, M. (Markus), Peters, A. (Annette), Peters, U. (Ulrike), Peyser, P. A. (Patricia A.), Prokopenko, I. (Inga), Puolijoki, H. (Hannu), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Rudan, I. (Igor), Sarti, C. (Cinzia), Sarzynski, M. A. (Mark A.), Savonen, K. (Kai), Scott, W. R. (William R.), Sanna, S. (Serena), Shuldiner, A. R. (Alan R.), Sidney, S. (Steve), Silbernagel, G. (Guenther), Smith, B. H. (Blair H.), Smith, J. A. (Jennifer A.), Snieder, H. (Harold), Stancakova, A. (Alena), Sternfeld, B. (Barbara), Swift, A. J. (Amy J.), Tammelin, T. (Tuija), Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Vandenput, L. (Liesbeth), Vestergaard, H. (Henrik), van Vliet-Ostaptchouk, J. V. (Jana V.), Vohl, M.-C. (Marie-Claude), Voelker, U. (Uwe), Waeber, G. (Gerard), Walker, M. (Mark), Wild, S. (Sarah), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zillikens, M. C. (M. Carola), Zubair, N. (Niha), Haiman, C. A. (Christopher A.), Lemarchand, L. (Loic), Gyllensten, U. (Ulf), Ohlsson, C. (Claes), Hofman, A. (Albert), Rivadeneira, F. (Fernando), Uitterlinden, A. G. (Andre G.), Perusse, L. (Louis), Wilson, J. F. (James F.), Hayward, C. (Caroline), Polasek, O. (Ozren), Cucca, F. (Francesco), Hveem, K. (Kristian), Hartman, C. A. (Catharina A.), Toenjes, A. (Anke), Bandinelli, S. (Stefania), Palmer, L. J. (Lyle J.), Kardia, S. L. (Sharon L. R.), Rauramaa, R. (Rainer), Sorensen, T. I. (Thorkild I. A.), Tuomilehto, J. (Jaakko), Salomaa, V. (Veikko), Penninx, B. W. (Brenda W. J. H.), de Geus, E. J. (Eco J. C.), Boomsma, D. I. (Dorret I.), Lehtimaki, T. (Terho), Mangino, M. (Massimo), Laakso, M. (Markku), Bouchard, C. (Claude), Martin, N. G. (Nicholas G.), Kuh, D. (Diana), Liu, Y. (Yongmei), Linneberg, A. (Allan), Maerz, W. (Winfried), Strauch, K. (Konstantin), Kivimaki, M. (Mika), Harris, T. B. (Tamara B.), Gudnason, V. (Vilmundur), Voelzke, H. (Henry), Qi, L. (Lu), Jarvelin, M.-R. (Marjo-Riitta), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), Froguel, P. (Philippe), Kooperberg, C. (Charles), Vollenweider, P. (Peter), Hallmans, G. (Goran), Hansen, T. (Torben), Pedersen, O. (Oluf), Metspalu, A. (Andres), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Weir, D. R. (David R.), Porteous, D. J. (David J.), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel I.), Abecasis, G. R. (Goncalo R.), Barroso, I. (Ines), McCarthy, M. I. (Mark I.), Frayling, T. M. (Timothy M.), O'Connell, J. R. (Jeffrey R.), van Duijn, C. M. (Cornelia M.), Boehnke, M. (Michael), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Strachan, D. P. (David P.), Fox, C. S. (Caroline S.), Liu, C.-T. (Ching-Ti), Hirschhorn, J. N. (Joel N.), Klein, R. J. (Robert J.), Johnson, A. D. (Andrew D.), Borecki, I. B. (Ingrid B.), Franks, P. W. (Paul W.), North, K. E. (Kari E.), Cupples, L. A. (L. Adrienne), Loos, R. J. (Ruth J. F.), Kilpelainen, T. O. (Tuomas O.), Graff, M. (Mariaelisa), Scott, R. A. (Robert A.), Justice, A. E. (Anne E.), Young, K. L. (Kristin L.), Feitosa, M. F. (Mary F.), Barata, L. (Llilda), Winkler, T. W. (Thomas W.), Chu, A. Y. (Audrey Y.), Mahajan, A. (Anubha), Hadley, D. (David), Xue, L. (Luting), Workalemahu, T. (Tsegaselassie), Heard-Costa, N. L. (Nancy L.), den Hoed, M. (Marcel), Ahluwalia, T. S. (Tarunveer S.), Qi, Q. (Qibin), Ngwa, J. S. (Julius S.), Renstrom, F. (Frida), Quaye, L. (Lydia), Eicher, J. D. (John D.), Hayes, J. E. (James E.), Cornelis, M. (Marilyn), Kutalik, Z. (Zoltan), Lim, E. (Elise), Luan, J. (Jian'an), Huffman, J. E. (Jennifer E.), Zhang, W. (Weihua), Zhao, W. (Wei), Griffin, P. J. (Paula J.), Haller, T. (Toomas), Ahmad, S. (Shafqat), Marques-Vidal, P. M. (Pedro M.), Bien, S. (Stephanie), Yengo, L. (Loic), Teumer, A. (Alexander), Smith, A. V. (Albert Vernon), Kumari, M. (Meena), Harder, M. N. (Marie Neergaard), Justesen, J. M. (Johanne Marie), Kleber, M. E. (Marcus E.), Hollensted, M. (Mette), Lohman, K. (Kurt), Rivera, N. V. (Natalia V.), Whitfield, J. B. (John B.), Zhao, J. H. (Jing Hua), Stringham, H. M. (Heather M.), Lyytikainen, L.-P. (Leo-Pekka), Huppertz, C. (Charlotte), Willemsen, G. (Gonneke), Peyrot, W. J. (Wouter J.), Wu, Y. (Ying), Kristiansson, K. (Kati), Demirkan, A. (Ayse), Fornage, M. (Myriam), Hassinen, M. (Maija), Bielak, L. F. (Lawrence F.), Cadby, G. (Gemma), Tanaka, T. (Toshiko), Magl, R. (Reedlk), Van der Most, P. J. (Peter J.), Jackson, A. U. (Anne U.), Bragg-Gresham, J. L. (Jennifer L.), Vitart, V. (Veronique), Marten, J. (Jonathan), Navarro, P. (Pau), Bellis, C. (Claire), Pasko, D. (Dorota), Johansson, A. (Asa), Snitker, S. (Soren), Cheng, Y.-C. (Yu-Ching), Eriksson, J. (Joel), Lim, U. (Unhee), Aadahl, M. (Mette), Adair, L. S. (Linda S.), Amin, N. (Najaf), Balkau, B. (Beverley), Auvinen, J. (Juha), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Bertoni, A. G. (Alain G.), Blangero, J. (John), Bonnefond, A. (Amelle), Bonnycastle, L. L. (Lori L.), Borja, J. B. (Judith B.), Brage, S. (Soren), Busonero, F. (Fabio), Buyske, S. (Steve), Campbell, H. (Harry), Chines, P. S. (Peter S.), Collins, F. S. (Francis S.), Corre, T. (Tanguy), Smith, G. D. (George Davey), Delgado, G. E. (Graciela E.), Dueker, N. (Nicole), Doerr, M. (Marcus), Ebeling, T. (Tapani), Eiriksdottir, G. (Gudny), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Fu, M. (Mao), Faerch, K. (Kristine), Gieger, C. (Christian), Glaeser, S. (Sven), Gong, J. (Jian), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), van Grootheest, G. (Gerard), Harald, K. (Kennet), Hastie, N. D. (Nicholas D.), Havulinna, A. S. (Aki S.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Holmens, O. L. (Oddgeir L.), Holzapfel, C. (Christina), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Huang, T. (Tao), Hui, J. (Jennie), Huth, C. (Cornelia), Hutri-Kahonen, N. (Nina), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Jhun, M. A. (Min A.), Juonala, M. (Markus), Kinnunen, L. (Leena), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Komulainen, P. (Pirjo), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Kahonen, M. (Mika), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Lehne, B. (Benjamin), Lindgren, C. M. (Cecilia M.), Lorentzon, M. (Mattias), Luben, R. (Robert), Marre, M. (Michel), Milaneschi, Y. (Yuri), Monda, K. L. (Keri L.), Montgomery, G. W. (Grant W.), De Moor, M. H. (Marleen H. M.), Mulas, A. (Antonella), Mueller-Nurasyid, M. (Martina), Musk, A. W. (A. W.), Mannikko, R. (Reija), Mannisto, S. (Satu), Narisu, N. (Narisu), Nauck, M. (Matthias), Nettleton, J. A. (Jennifer A.), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Paternoster, L. (Lavinia), Perez, J. (Jeremiah), Perola, M. (Markus), Peters, A. (Annette), Peters, U. (Ulrike), Peyser, P. A. (Patricia A.), Prokopenko, I. (Inga), Puolijoki, H. (Hannu), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Rudan, I. (Igor), Sarti, C. (Cinzia), Sarzynski, M. A. (Mark A.), Savonen, K. (Kai), Scott, W. R. (William R.), Sanna, S. (Serena), Shuldiner, A. R. (Alan R.), Sidney, S. (Steve), Silbernagel, G. (Guenther), Smith, B. H. (Blair H.), Smith, J. A. (Jennifer A.), Snieder, H. (Harold), Stancakova, A. (Alena), Sternfeld, B. (Barbara), Swift, A. J. (Amy J.), Tammelin, T. (Tuija), Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Vandenput, L. (Liesbeth), Vestergaard, H. (Henrik), van Vliet-Ostaptchouk, J. V. (Jana V.), Vohl, M.-C. (Marie-Claude), Voelker, U. (Uwe), Waeber, G. (Gerard), Walker, M. (Mark), Wild, S. (Sarah), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zillikens, M. C. (M. Carola), Zubair, N. (Niha), Haiman, C. A. (Christopher A.), Lemarchand, L. (Loic), Gyllensten, U. (Ulf), Ohlsson, C. (Claes), Hofman, A. (Albert), Rivadeneira, F. (Fernando), Uitterlinden, A. G. (Andre G.), Perusse, L. (Louis), Wilson, J. F. (James F.), Hayward, C. (Caroline), Polasek, O. (Ozren), Cucca, F. (Francesco), Hveem, K. (Kristian), Hartman, C. A. (Catharina A.), Toenjes, A. (Anke), Bandinelli, S. (Stefania), Palmer, L. J. (Lyle J.), Kardia, S. L. (Sharon L. R.), Rauramaa, R. (Rainer), Sorensen, T. I. (Thorkild I. A.), Tuomilehto, J. (Jaakko), Salomaa, V. (Veikko), Penninx, B. W. (Brenda W. J. H.), de Geus, E. J. (Eco J. C.), Boomsma, D. I. (Dorret I.), Lehtimaki, T. (Terho), Mangino, M. (Massimo), Laakso, M. (Markku), Bouchard, C. (Claude), Martin, N. G. (Nicholas G.), Kuh, D. (Diana), Liu, Y. (Yongmei), Linneberg, A. (Allan), Maerz, W. (Winfried), Strauch, K. (Konstantin), Kivimaki, M. (Mika), Harris, T. B. (Tamara B.), Gudnason, V. (Vilmundur), Voelzke, H. (Henry), Qi, L. (Lu), Jarvelin, M.-R. (Marjo-Riitta), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), Froguel, P. (Philippe), Kooperberg, C. (Charles), Vollenweider, P. (Peter), Hallmans, G. (Goran), Hansen, T. (Torben), Pedersen, O. (Oluf), Metspalu, A. (Andres), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Weir, D. R. (David R.), Porteous, D. J. (David J.), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel I.), Abecasis, G. R. (Goncalo R.), Barroso, I. (Ines), McCarthy, M. I. (Mark I.), Frayling, T. M. (Timothy M.), O'Connell, J. R. (Jeffrey R.), van Duijn, C. M. (Cornelia M.), Boehnke, M. (Michael), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Strachan, D. P. (David P.), Fox, C. S. (Caroline S.), Liu, C.-T. (Ching-Ti), Hirschhorn, J. N. (Joel N.), Klein, R. J. (Robert J.), Johnson, A. D. (Andrew D.), Borecki, I. B. (Ingrid B.), Franks, P. W. (Paul W.), North, K. E. (Kari E.), Cupples, L. A. (L. Adrienne), Loos, R. J. (Ruth J. F.), and Kilpelainen, T. O. (Tuomas O.)
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017

6. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, A. E. (Anne E.), Winkler, T. W. (Thomas W.), Feitosa, M. F. (Mary F.), Graff, M. (Misa), Fisher, V. A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J. S. (Julius S.), Ahluwalia, T. S. (Tarunveer S.), Chu, A. Y. (Audrey Y.), Heard-Costa, N. L. (Nancy L.), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J. D. (John D.), Kutalik, Z. (Zoltan), Xue, L. (Luting), Mahajan, A. (Anubha), Renstrom, F. (Frida), Wu, J. (Joseph), Qi, Q. (Qibin), Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L. F. (Lawrence F.), Bonnefond, A. (Amelie), Bragg, J. (Jennifer), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M. N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J. E. (Jennifer E.), Jackson, A. U. (Anne U.), Justesen, J. M. (Johanne Marie), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M. E. (Marcus E.), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R. P. (Rita P. S.), Mueller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A. V. (Albert Vernon), Smith, J. A. (Jennifer A.), Stancakova, A. (Alena), Strawbridge, R. J. (Rona J.), Stringham, H. M. (Heather M.), Sung, Y. J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), van der Laan, S. W. (Sander W.), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vedantam, S. L. (Sailaja L.), Verweij, N. (Niek), Vink, J. M. (Jacqueline M.), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zimmermann, M. E. (Martina E.), Zubair, N. (Niha), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S. J. (Stephan J. L.), Bartz, T. M. (Traci M.), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bottinger, E. (Erwin), Braga, D. (Daniele), Buckley, B. M. (Brendan M.), Buyske, S. (Steve), Campbell, H. (Harry), Chambers, J. C. (John C.), Collins, F. S. (Francis S.), Curran, J. E. (Joanne E.), de Borst, G. J. (Gert J.), de Craen, A. J. (Anton J. M.), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Delgado, G. E. (Graciela E.), den Ruijter, H. M. (Hester M.), Eiriksdottir, G. (Gudny), Eriksson, A. L. (Anna L.), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Goran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T. B. (Tamara B.), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. D. (Nicholas D.), Heath, A. C. (Andrew C.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Hollensted, M. (Mette), Holmen, O. L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Järvelin, M.-R. (Marjo-Riitta), Jhun, M. A. (Min A.), Jorgensen, M. E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Kramer, B. K. (Bernhard K.), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Leander, K. (Karin), Lee, N. R. (Nanette R.), Lind, L. (Lars), Lindgren, C. M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stephane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P. A. (Pamela A. F.), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N. G. (Nicholas G.), McKenzie, C. A. (Colin A.), McKnight, B. (Barbara), Mellstrom, D. (Dan), Menni, C. (Cristina), Montgomery, G. W. (Grant W.), Musk, A. W. (A. W. (Bill)), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P. A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D. J. (David J.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Rice, T. (Treva), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Bien, S. A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R. A. (Robert A.), Sennblad, B. (Bengt), Siemelink, M. A. (Marten A.), Silbernagel, G. (Gunther), Slagboom, P. E. (P. Eline), Snieder, H. (Harold), Staessen, J. A. (Jan A.), Stott, D. J. (David J.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Taylor, K. D. (Kent D.), Tayo, B. O. (Bamidele O.), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Volzke, H. (Henry), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Waldenberger, M. (Melanie), Westendorp, R. G. (R. G. J.), Wild, S. (Sarah), Willemsen, G. (Gonneke), Wolffenbuttel, B. H. (Bruce H. R.), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zhao, W. (Wei), Zillikens, M. C. (M. Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Boger, C. A. (Carsten A.), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Bruinenberg, M. (Marcel), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Chines, P. S. (Peter S.), Cooper, R. S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), de Faire, U. (Ulf), Ferrucci, L. (Luigi), Franks, P. W. (Paul W.), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.-J. (Hans-Jorgen), Gudnason, V. (Vilmundur), Haiman, C. A. (Christopher A.), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A. D. (Andrew D.), Jukema, W. (Wouter), Kardia, S. L. (Sharon L. R.), Kivimäki, M. (Mika), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), Marz, W. (Winfried), McCarthy, M. I. (Mark I.), Metspalu, A. (Andres), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Palmer, L. J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B. H. (Blair H.), Sorensen, T. I. (Thorkild I. A.), Strauch, K. (Konstantin), Tiemeier, H. (Henning), Tremoli, E. (Elena), Van der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wilson, J. F. (James F.), Tyrrell, J. (Jessica), Frayling, T. M. (Timothy M.), Barroso, I. (Ines), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C. S. (Caroline S.), Hirschhorn, J. N. (Joel N.), Hunter, D. J. (David J.), Spector, T. D. (Tim D.), Strachan, D. P. (David P.), van Duijn, C. M. (Cornelia M.), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Marchini, J. (Jonathan), Loos, R. J. (Ruth J. F.), Kilpeläinen, T. O. (Tuomas O.), Liu, C.-T. (Ching-Ti), Borecki, I. B. (Ingrid B.), North, K. E. (Kari E.), Cupples, L. A. (L. Adrienne), Justice, A. E. (Anne E.), Winkler, T. W. (Thomas W.), Feitosa, M. F. (Mary F.), Graff, M. (Misa), Fisher, V. A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J. S. (Julius S.), Ahluwalia, T. S. (Tarunveer S.), Chu, A. Y. (Audrey Y.), Heard-Costa, N. L. (Nancy L.), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J. D. (John D.), Kutalik, Z. (Zoltan), Xue, L. (Luting), Mahajan, A. (Anubha), Renstrom, F. (Frida), Wu, J. (Joseph), Qi, Q. (Qibin), Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L. F. (Lawrence F.), Bonnefond, A. (Amelie), Bragg, J. (Jennifer), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M. N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J. E. (Jennifer E.), Jackson, A. U. (Anne U.), Justesen, J. M. (Johanne Marie), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M. E. (Marcus E.), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R. P. (Rita P. S.), Mueller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A. V. (Albert Vernon), Smith, J. A. (Jennifer A.), Stancakova, A. (Alena), Strawbridge, R. J. (Rona J.), Stringham, H. M. (Heather M.), Sung, Y. J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), van der Laan, S. W. (Sander W.), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vedantam, S. L. (Sailaja L.), Verweij, N. (Niek), Vink, J. M. (Jacqueline M.), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zimmermann, M. E. (Martina E.), Zubair, N. (Niha), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S. J. (Stephan J. L.), Bartz, T. M. (Traci M.), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bottinger, E. (Erwin), Braga, D. (Daniele), Buckley, B. M. (Brendan M.), Buyske, S. (Steve), Campbell, H. (Harry), Chambers, J. C. (John C.), Collins, F. S. (Francis S.), Curran, J. E. (Joanne E.), de Borst, G. J. (Gert J.), de Craen, A. J. (Anton J. M.), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Delgado, G. E. (Graciela E.), den Ruijter, H. M. (Hester M.), Eiriksdottir, G. (Gudny), Eriksson, A. L. (Anna L.), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Goran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T. B. (Tamara B.), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. D. (Nicholas D.), Heath, A. C. (Andrew C.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Hollensted, M. (Mette), Holmen, O. L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Järvelin, M.-R. (Marjo-Riitta), Jhun, M. A. (Min A.), Jorgensen, M. E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Kramer, B. K. (Bernhard K.), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Leander, K. (Karin), Lee, N. R. (Nanette R.), Lind, L. (Lars), Lindgren, C. M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stephane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P. A. (Pamela A. F.), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N. G. (Nicholas G.), McKenzie, C. A. (Colin A.), McKnight, B. (Barbara), Mellstrom, D. (Dan), Menni, C. (Cristina), Montgomery, G. W. (Grant W.), Musk, A. W. (A. W. (Bill)), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P. A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D. J. (David J.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Rice, T. (Treva), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Bien, S. A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R. A. (Robert A.), Sennblad, B. (Bengt), Siemelink, M. A. (Marten A.), Silbernagel, G. (Gunther), Slagboom, P. E. (P. Eline), Snieder, H. (Harold), Staessen, J. A. (Jan A.), Stott, D. J. (David J.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Taylor, K. D. (Kent D.), Tayo, B. O. (Bamidele O.), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Volzke, H. (Henry), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Waldenberger, M. (Melanie), Westendorp, R. G. (R. G. J.), Wild, S. (Sarah), Willemsen, G. (Gonneke), Wolffenbuttel, B. H. (Bruce H. R.), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zhao, W. (Wei), Zillikens, M. C. (M. Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Boger, C. A. (Carsten A.), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Bruinenberg, M. (Marcel), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Chines, P. S. (Peter S.), Cooper, R. S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), de Faire, U. (Ulf), Ferrucci, L. (Luigi), Franks, P. W. (Paul W.), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.-J. (Hans-Jorgen), Gudnason, V. (Vilmundur), Haiman, C. A. (Christopher A.), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A. D. (Andrew D.), Jukema, W. (Wouter), Kardia, S. L. (Sharon L. R.), Kivimäki, M. (Mika), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), Marz, W. (Winfried), McCarthy, M. I. (Mark I.), Metspalu, A. (Andres), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Palmer, L. J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B. H. (Blair H.), Sorensen, T. I. (Thorkild I. A.), Strauch, K. (Konstantin), Tiemeier, H. (Henning), Tremoli, E. (Elena), Van der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wilson, J. F. (James F.), Tyrrell, J. (Jessica), Frayling, T. M. (Timothy M.), Barroso, I. (Ines), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C. S. (Caroline S.), Hirschhorn, J. N. (Joel N.), Hunter, D. J. (David J.), Spector, T. D. (Tim D.), Strachan, D. P. (David P.), van Duijn, C. M. (Cornelia M.), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Marchini, J. (Jonathan), Loos, R. J. (Ruth J. F.), Kilpeläinen, T. O. (Tuomas O.), Liu, C.-T. (Ching-Ti), Borecki, I. B. (Ingrid B.), North, K. E. (Kari E.), and Cupples, L. A. (L. Adrienne)
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Published: 2017

7. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Ehret, G.B. (Georg), Ferreira, T. (Teresa), Chasman, D.I. (Daniel), Jackson, A.U. (Anne), Schmidt, E.M. (Ellen), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'An), Donnelly, L.A. (Louise), Kanoni, S. (Stavroula), Petersen, A.K., Pihur, V. (Vasyl), Strawbridge, R.J. (Rona), Shungin, D. (Dmitry), Hughes, M.F. (Maria F.), Meirelles, O., Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Lyytikäinen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Niclas), Nolte, I.M. (Ilja), Magnusson, P.K. (Patrik), Salfati, E. (Elias), Rallidis, L.S. (Loukianos), Theusch, E. (Elizabeth), Smith, A.J. (Andrew), Folkersen, L. (Lasse), Witkowska, H.E. (Ewa), Pers, T.H. (Tune), Joehanes, R. (Roby), Kim, S.K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R., Johnson, A.D. (Andrew), Warren, H. (Helen), Kim, Y.J., Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. (Bamidele), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L.S. (Linda), Amin, N. (Najaf), Arking, D.E. (Dan), Axelsson, T. (Tomas), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M.J. (Michael), Barroso, I.E. (Inês), Bevan, S. (Stephen), Bis, J.C. (Joshua), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Burnier, M. (Michel), Cabrera, C.P. (Claudia P.), Chambers, J.C. (John), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P.S. (Peter), Chung, R.-H. (Ren-Hua), Collins, F.S. (Francis), Connell, J.M. (John M.), Döring, A. (Angela), Dallongeville, J., Danesh, J. (John), Faire, U. (Ulf) de, Delgado, G., Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Drenos, F. (Fotios), Edkins, T. (Ted), Eicher, J.D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tõnu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fall, M. (Magnus), Farrall, M. (Martin), Felix, J.F. (Janine), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschini, N. (Nora), Franco, O.H. (Oscar), Franco-Cereceda, A. (Anders), Fraser, R.M. (Ross), Ganesh, S.K. (Santhi), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goel, A. (Anuj), Goodall, A.H. (Alison), Goodarzi, M. (Mark), Gorski, M. (Mathias), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Göran), Hartikainen, A.L., Hassinen, M. (Maija), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.H., Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holmen, J. (Jostein), Holmen, O.L. (Oddgeir), Hottenga, J.J. (Jouke Jan), Howard, P. (Philip), Hsiung, C.A. (Chao A.), Hunt, S.C. (Steven), Ikram, M.K. (Kamran), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R.A. (Richard A.), Kähönen, M. (Mika), Kang, H.M. (Hyun Min), Kathiresan, S. (Sekar), Keating, J. (John), Khaw, K.T., Kim, Y.K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J.S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R.M. (Ronald), Kuh, D. (Diana), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Lee, N.R. (Nanette), Lee, I.T., Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Männistö, S. (Satu), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), MacH, F. (François), Markus, H.S. (Hugh), Marouli, E. (Eirini), McCarthy, M.I. (Mark), McKenzie, C.A. (Colin), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M.E. (May E.), Morris, A.D. (Andrew), Morrison, A.C. (Alanna), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), O'Reilly, P.F. (Paul), Ong, K.K. (Ken), Paccaud, F. (Fred), Palmer, C. (Cameron), Parsa, A. (Afshin), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rao, D.C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Roberts, R. (Robert), Rose, L.M. (Lynda), Rossouw, J. (Jacques), Samani, N.J. (Nilesh), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W.H.-H. (Wayne H.-H.), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smith, A.V. (Davey), Smith, A.V. (Albert Vernon), Sosa, M.X. (Maria X.), Spector, T.D. (Timothy), Stancáková, A. (Alena), Stanton, A. (Alice), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swift, A.J. (Amy), Syvänen, A.C., Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K.V. (Kirill), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M.D. (Martin), Tremoli, E. (Elena), Uitterlinden, A.G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), Van Duijn, C.M. (Cornelia M.), Iperen, E.P.A. (Erik) van, Vasan, R.S. (Ramachandran S.), Verwoert, G.C. (Germaine), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B.F. (Benjamin), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L.V. (Louise V.), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weder, A.B. (Alan), Westra, H.J. (Harm-Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J.F. (James F.), Wong, T.Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jiefen), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R.S. (Richard S.), Mohlke, K.L. (Karen), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, L.M. (Lobke), Willer, C.J. (Cristen), Franke, L. (Lude), Hovingh, G.K. (Kees), Taylor, K.D. (Kent), Dedoussis, G.V. (George), Sever, P. (Peter), Wong, A. (Andrew), Kao, W.H.L. (Wen), Assimes, T.L. (Themistocles), Njølstad, I. (Inger), Schwarz, P.E.H. (Peter), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. (Mark), Melander, O. (Olle), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), März, W. (Winfried), Kumari, M. (Meena), Salomaa, V. (Veikko), Chen, Y.D. (Y.), Rotter, J.I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. (Edward), Kuulasmaa, K. (Kari), Franks, P.W. (Paul), Hamsten, A. (Anders), Wichmann, H.E. (Heinz Erich), Palmer, C.N.A. (Colin), Stefansson, K. (Kari), Ridker, P.M. (Paul), Loos, R.J.F. (Ruth), Chakravarti, A. (Aravinda), Deloukas, P. (Panagiotis), Morris, A.P. (Andrew), Newton-Cheh, C. (C.), Munroe, P. (Patricia), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Chasman, D.I. (Daniel), Jackson, A.U. (Anne), Schmidt, E.M. (Ellen), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'An), Donnelly, L.A. (Louise), Kanoni, S. (Stavroula), Petersen, A.K., Pihur, V. (Vasyl), Strawbridge, R.J. (Rona), Shungin, D. (Dmitry), Hughes, M.F. (Maria F.), Meirelles, O., Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Lyytikäinen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Niclas), Nolte, I.M. (Ilja), Magnusson, P.K. (Patrik), Salfati, E. (Elias), Rallidis, L.S. (Loukianos), Theusch, E. (Elizabeth), Smith, A.J. (Andrew), Folkersen, L. (Lasse), Witkowska, H.E. (Ewa), Pers, T.H. (Tune), Joehanes, R. (Roby), Kim, S.K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R., Johnson, A.D. (Andrew), Warren, H. (Helen), Kim, Y.J., Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. (Bamidele), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L.S. (Linda), Amin, N. (Najaf), Arking, D.E. (Dan), Axelsson, T. (Tomas), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M.J. (Michael), Barroso, I.E. (Inês), Bevan, S. (Stephen), Bis, J.C. (Joshua), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Burnier, M. (Michel), Cabrera, C.P. (Claudia P.), Chambers, J.C. (John), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P.S. (Peter), Chung, R.-H. (Ren-Hua), Collins, F.S. (Francis), Connell, J.M. (John M.), Döring, A. (Angela), Dallongeville, J., Danesh, J. (John), Faire, U. (Ulf) de, Delgado, G., Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Drenos, F. (Fotios), Edkins, T. (Ted), Eicher, J.D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tõnu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fall, M. (Magnus), Farrall, M. (Martin), Felix, J.F. (Janine), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschini, N. (Nora), Franco, O.H. (Oscar), Franco-Cereceda, A. (Anders), Fraser, R.M. (Ross), Ganesh, S.K. (Santhi), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goel, A. (Anuj), Goodall, A.H. (Alison), Goodarzi, M. (Mark), Gorski, M. (Mathias), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Göran), Hartikainen, A.L., Hassinen, M. (Maija), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.H., Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holmen, J. (Jostein), Holmen, O.L. (Oddgeir), Hottenga, J.J. (Jouke Jan), Howard, P. (Philip), Hsiung, C.A. (Chao A.), Hunt, S.C. (Steven), Ikram, M.K. (Kamran), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R.A. (Richard A.), Kähönen, M. (Mika), Kang, H.M. (Hyun Min), Kathiresan, S. (Sekar), Keating, J. (John), Khaw, K.T., Kim, Y.K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J.S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R.M. (Ronald), Kuh, D. (Diana), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Lee, N.R. (Nanette), Lee, I.T., Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Männistö, S. (Satu), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), MacH, F. (François), Markus, H.S. (Hugh), Marouli, E. (Eirini), McCarthy, M.I. (Mark), McKenzie, C.A. (Colin), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M.E. (May E.), Morris, A.D. (Andrew), Morrison, A.C. (Alanna), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), O'Reilly, P.F. (Paul), Ong, K.K. (Ken), Paccaud, F. (Fred), Palmer, C. (Cameron), Parsa, A. (Afshin), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rao, D.C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Roberts, R. (Robert), Rose, L.M. (Lynda), Rossouw, J. (Jacques), Samani, N.J. (Nilesh), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W.H.-H. (Wayne H.-H.), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smith, A.V. (Davey), Smith, A.V. (Albert Vernon), Sosa, M.X. (Maria X.), Spector, T.D. (Timothy), Stancáková, A. (Alena), Stanton, A. (Alice), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swift, A.J. (Amy), Syvänen, A.C., Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K.V. (Kirill), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M.D. (Martin), Tremoli, E. (Elena), Uitterlinden, A.G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), Van Duijn, C.M. (Cornelia M.), Iperen, E.P.A. (Erik) van, Vasan, R.S. (Ramachandran S.), Verwoert, G.C. (Germaine), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B.F. (Benjamin), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L.V. (Louise V.), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weder, A.B. (Alan), Westra, H.J. (Harm-Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J.F. (James F.), Wong, T.Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jiefen), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R.S. (Richard S.), Mohlke, K.L. (Karen), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, L.M. (Lobke), Willer, C.J. (Cristen), Franke, L. (Lude), Hovingh, G.K. (Kees), Taylor, K.D. (Kent), Dedoussis, G.V. (George), Sever, P. (Peter), Wong, A. (Andrew), Kao, W.H.L. (Wen), Assimes, T.L. (Themistocles), Njølstad, I. (Inger), Schwarz, P.E.H. (Peter), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. (Mark), Melander, O. (Olle), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), März, W. (Winfried), Kumari, M. (Meena), Salomaa, V. (Veikko), Chen, Y.D. (Y.), Rotter, J.I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. (Edward), Kuulasmaa, K. (Kari), Franks, P.W. (Paul), Hamsten, A. (Anders), Wichmann, H.E. (Heinz Erich), Palmer, C.N.A. (Colin), Stefansson, K. (Kari), Ridker, P.M. (Paul), Loos, R.J.F. (Ruth), Chakravarti, A. (Aravinda), Deloukas, P. (Panagiotis), Morris, A.P. (Andrew), Newton-Cheh, C. (C.), and Munroe, P. (Patricia)
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Published: 2016
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8. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Author: Surendran, P. (Praveen), Drenos, F. (Fotios), Young, R. (Robin), Warren, H. (Helen), Cook, J.P. (James P.), Manning, A.K. (Alisa), Grarup, N. (Niels), Sim, X. (Xueling), Barnes, D. (Daniel), Witkowska, H.E. (Ewa), Staley, J.R. (James R.), Tragante, V. (Vinicius), Tukiainen, T. (Taru), Yaghootkar, H. (Hanieh), Masca, N. (Nicholas), Freitag, C.M. (Christine), Ferreira, T. (Teresa), Giannakopoulou, O. (Olga), Tinker, A. (Andrew), Harakalova, M. (Magdalena), Mihailov, E. (Evelin), Liu, C. (Chunyu), Kraja, A. (Aldi), Nielsen, S.F. (Sune), Rasheed, A. (Asif), Samuel, M. (Maria), Zhao, W. (Wei), Bonnycastle, L.L. (Lori), Jackson, A.U. (Anne), Narisu, N. (Narisu), Swift, A.J. (Amy), Southam, L. (Lorraine), Marten, J. (Jonathan), Huyghe, J.R. (Jeroen R.), Stancáková, A. (Alena), Fava, C. (Cristiano), Ohlsson, T. (Therese), Matchan, A. (Angela), Stirrups, K. (Kathy), Bork-Jensen, J. (Jette), Gjesing, A.P. (Anette), Kontto, J. (Jukka), Perola, M. (Markus), Shaw-Hawkins, S. (Sue), Havulinna, A.S. (Aki), Zhang, H. (He), Donnelly, L.A. (Louise), Groves, C.J. (Christopher), Rayner, N.W. (Nigel William), Neville, M.J. (Matthew), Robertson, N.R. (Neil), Yiorkas, A.M. (Andrianos M.), Herzig, K.H., Kajantie, E. (Eero), Zhang, W. (Weihua), Willems, S.M. (Sara), Lannfelt, L. (Lars), Malerba, G. (Giovanni), Soranzo, N. (Nicole), Trabetti, E. (Elisabetta), Verweij, N. (Niek), Evangelou, E. (Evangelos), Moayyeri, A. (Alireza), Vergnaud, A.-C. (Anne-Claire), Nelson, C.P. (Christopher P.), Poveda, A. (Alaitz), Varga, T.V. (Tibor V.), Caslake, M. (Muriel), De Craen, A.J.M. (Anton J. M.), Trompet, S. (Stella), Luan, J. (Jian'An), Scott, R.A. (Robert), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Marioni, R.E. (Riccardo), Menni, C. (Cristina), Farmaki, A.-E. (Aliki-Eleni), Hallmans, G. (Göran), Renström, F. (Frida), Huffman, J.E. (Jennifer), Hassinen, M. (Maija), Burgess, S. (Stephen), Vasan, R.S. (Ramachandran S.), Felix, J.F. (Janine), Uria-Nickelsen, M. (Maria), Mälarstig, A. (Anders), Reilly, D.F. (Dermot F.), Hoek, M. (Maarten), Vogt, T.F. (Thomas F.), Lin, H. (Honghuang), Lieb, W. (Wolfgang), Traylor, M. (Matthew), Markus, H.S. (Hugh), Highland, H. (Heather), Justice, A.E. (Anne), Marouli, E. (Eirini), Lindström, J. (Jaana), Uusitupa, M. (Matti), Komulainen, P. (Pirjo), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Polasek, O. (Ozren), Rudan, I. (Igor), Rolandsson, O. (Olov), Franks, P.W. (Paul), Dedoussis, G.V. (George), Spector, T.D. (Timothy), Jousilahti, P. (Pekka), Männistö, S. (Satu), Deary, I.J. (Ian), Starr, J.M. (John), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Brown, M.J. (Morris), Dominiczak, A. (Anna), Connell, J.M. (John M.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Ford, I. (Ian), Packard, C.J. (Chris J.), Esko, T. (Tõnu), Mägi, R. (Reedik), Metspalu, A. (Andres), Boer, R.A. (Rudolf) de, Van Der Meer, P. (Peter), Harst, P. (Pim) van der, Gambaro, G. (Giovanni), Ingelsson, E. (Erik), Kao, W.H.L. (Wen), Bakker, P.I.W. (Paul) de, Numans, M.E. (Mattijs), Brandslund, I. (Ivan), Christensen, C. (Cramer), Petersen, E.R.B. (Eva R. B.), Korpi-Hyövälti, E. (Eeva), Oksa, H. (Heikki), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Blakemore, A.I.F. (Alexandra), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Husemoen, L.L.N. (Lise Lotte), Linneberg, A. (Allan), Skaaby, T. (Tea), Thuesen, B. (Betina), Karpe, F. (Fredrik), Tuomilehto, J. (Jaakko), Doney, A.S.F. (Alex), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Holmen, O.L. (Oddgeir), Hveem, K. (Kristian), Willer, C.J. (Cristen), Tuomi, T. (Tiinamaija), Groop, L. (Leif), Käräjämäki, A. (Annemari), Palotie, A. (Aarno), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Alam, D.S. (Dewan S.), Majumder, A.A.S. (Abdulla Al Shafi), Angelantonio, E. (Emanuele) di, Chowdhury, R. (Rajiv), McCarthy, M.I. (Mark), Poulter, N.R. (Neil), Stanton, A. (Alice), Sever, P. (Peter), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Blankenberg, S. (Stefan), Ferrieres, J. (Jean), Kee, F. (Frank), Kuulasmaa, K. (Kari), Müller-Nurasyid, M. (Martina), Veronesi, G. (Giovanni), Virtamo, J. (Jarmo), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Zeggini, E. (Eleftheria), Kathiresan, S. (Sekar), Melander, O. (Olle), Kuusisto, J. (Johanna), Laakso, M. (Markku), Padmanabhan, S. (Sandosh), Porteous, D. (David), Hayward, C. (Caroline), Scotland, G. (Generation), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Hansen, T. (T.), Pedersen, O. (Oluf), Boehnke, M. (Michael), Stringham, H.M. (Heather), Frossard, R., Newton-Cheh, C. (Christopher), Tobin, M.D. (Martin), Nordestgaard, B.G. (Børge), Caulfield, M. (Mark), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Tomaszewski, M. (Maciej), Samani, N.J. (Nilesh), Saleheen, D. (Danish), Asselbergs, F.W. (Folkert), Lindgren, C.M. (Cecilia M.), Danesh, J. (John), Wain, L.V. (Louise V.), Butterworth, A.S. (Adam), Howson, J.M.M. (Joanna M. M.), Munroe, P. (Patricia), Surendran, P. (Praveen), Drenos, F. (Fotios), Young, R. (Robin), Warren, H. (Helen), Cook, J.P. (James P.), Manning, A.K. (Alisa), Grarup, N. (Niels), Sim, X. (Xueling), Barnes, D. (Daniel), Witkowska, H.E. (Ewa), Staley, J.R. (James R.), Tragante, V. (Vinicius), Tukiainen, T. (Taru), Yaghootkar, H. (Hanieh), Masca, N. (Nicholas), Freitag, C.M. (Christine), Ferreira, T. (Teresa), Giannakopoulou, O. (Olga), Tinker, A. (Andrew), Harakalova, M. (Magdalena), Mihailov, E. (Evelin), Liu, C. (Chunyu), Kraja, A. (Aldi), Nielsen, S.F. (Sune), Rasheed, A. (Asif), Samuel, M. (Maria), Zhao, W. (Wei), Bonnycastle, L.L. (Lori), Jackson, A.U. (Anne), Narisu, N. (Narisu), Swift, A.J. (Amy), Southam, L. (Lorraine), Marten, J. (Jonathan), Huyghe, J.R. (Jeroen R.), Stancáková, A. (Alena), Fava, C. (Cristiano), Ohlsson, T. (Therese), Matchan, A. (Angela), Stirrups, K. (Kathy), Bork-Jensen, J. (Jette), Gjesing, A.P. (Anette), Kontto, J. (Jukka), Perola, M. (Markus), Shaw-Hawkins, S. (Sue), Havulinna, A.S. (Aki), Zhang, H. (He), Donnelly, L.A. (Louise), Groves, C.J. (Christopher), Rayner, N.W. (Nigel William), Neville, M.J. (Matthew), Robertson, N.R. (Neil), Yiorkas, A.M. (Andrianos M.), Herzig, K.H., Kajantie, E. (Eero), Zhang, W. (Weihua), Willems, S.M. (Sara), Lannfelt, L. (Lars), Malerba, G. (Giovanni), Soranzo, N. (Nicole), Trabetti, E. (Elisabetta), Verweij, N. (Niek), Evangelou, E. (Evangelos), Moayyeri, A. (Alireza), Vergnaud, A.-C. (Anne-Claire), Nelson, C.P. (Christopher P.), Poveda, A. (Alaitz), Varga, T.V. (Tibor V.), Caslake, M. (Muriel), De Craen, A.J.M. (Anton J. M.), Trompet, S. (Stella), Luan, J. (Jian'An), Scott, R.A. (Robert), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Marioni, R.E. (Riccardo), Menni, C. (Cristina), Farmaki, A.-E. (Aliki-Eleni), Hallmans, G. (Göran), Renström, F. (Frida), Huffman, J.E. (Jennifer), Hassinen, M. (Maija), Burgess, S. (Stephen), Vasan, R.S. (Ramachandran S.), Felix, J.F. (Janine), Uria-Nickelsen, M. (Maria), Mälarstig, A. (Anders), Reilly, D.F. (Dermot F.), Hoek, M. (Maarten), Vogt, T.F. (Thomas F.), Lin, H. (Honghuang), Lieb, W. (Wolfgang), Traylor, M. (Matthew), Markus, H.S. (Hugh), Highland, H. (Heather), Justice, A.E. (Anne), Marouli, E. (Eirini), Lindström, J. (Jaana), Uusitupa, M. (Matti), Komulainen, P. (Pirjo), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Polasek, O. (Ozren), Rudan, I. (Igor), Rolandsson, O. (Olov), Franks, P.W. (Paul), Dedoussis, G.V. (George), Spector, T.D. (Timothy), Jousilahti, P. (Pekka), Männistö, S. (Satu), Deary, I.J. (Ian), Starr, J.M. (John), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Brown, M.J. (Morris), Dominiczak, A. (Anna), Connell, J.M. (John M.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Ford, I. (Ian), Packard, C.J. (Chris J.), Esko, T. (Tõnu), Mägi, R. (Reedik), Metspalu, A. (Andres), Boer, R.A. (Rudolf) de, Van Der Meer, P. (Peter), Harst, P. (Pim) van der, Gambaro, G. (Giovanni), Ingelsson, E. (Erik), Kao, W.H.L. (Wen), Bakker, P.I.W. (Paul) de, Numans, M.E. (Mattijs), Brandslund, I. (Ivan), Christensen, C. (Cramer), Petersen, E.R.B. (Eva R. B.), Korpi-Hyövälti, E. (Eeva), Oksa, H. (Heikki), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Blakemore, A.I.F. (Alexandra), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Husemoen, L.L.N. (Lise Lotte), Linneberg, A. (Allan), Skaaby, T. (Tea), Thuesen, B. (Betina), Karpe, F. (Fredrik), Tuomilehto, J. (Jaakko), Doney, A.S.F. (Alex), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Holmen, O.L. (Oddgeir), Hveem, K. (Kristian), Willer, C.J. (Cristen), Tuomi, T. (Tiinamaija), Groop, L. (Leif), Käräjämäki, A. (Annemari), Palotie, A. (Aarno), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Alam, D.S. (Dewan S.), Majumder, A.A.S. (Abdulla Al Shafi), Angelantonio, E. (Emanuele) di, Chowdhury, R. (Rajiv), McCarthy, M.I. (Mark), Poulter, N.R. (Neil), Stanton, A. (Alice), Sever, P. (Peter), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Blankenberg, S. (Stefan), Ferrieres, J. (Jean), Kee, F. (Frank), Kuulasmaa, K. (Kari), Müller-Nurasyid, M. (Martina), Veronesi, G. (Giovanni), Virtamo, J. (Jarmo), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Zeggini, E. (Eleftheria), Kathiresan, S. (Sekar), Melander, O. (Olle), Kuusisto, J. (Johanna), Laakso, M. (Markku), Padmanabhan, S. (Sandosh), Porteous, D. (David), Hayward, C. (Caroline), Scotland, G. (Generation), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Hansen, T. (T.), Pedersen, O. (Oluf), Boehnke, M. (Michael), Stringham, H.M. (Heather), Frossard, R., Newton-Cheh, C. (Christopher), Tobin, M.D. (Martin), Nordestgaard, B.G. (Børge), Caulfield, M. (Mark), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Tomaszewski, M. (Maciej), Samani, N.J. (Nilesh), Saleheen, D. (Danish), Asselbergs, F.W. (Folkert), Lindgren, C.M. (Cecilia M.), Danesh, J. (John), Wain, L.V. (Louise V.), Butterworth, A.S. (Adam), Howson, J.M.M. (Joanna M. M.), and Munroe, P. (Patricia)
Abstract: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
Published: 2016
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9. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author: Ried, J.S. (Janina), Jeff, J. (Janina), Chu, A.Y. (Audrey Y), Bragg-Gresham, J.L. (Jennifer L.), Dongen, J. (Jenny) van, Huffman, J.E. (Jennifer), Ahluwalia, T.S. (Tarunveer Singh), Cadby, G. (Gemma), Eklund, N. (Niina), Eriksson, J. (Joel), Esko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Gorski, M. (Mathias), Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Jackson, A.U. (Anne), Jokinen, E. (Eero), Kanoni, S. (Stavroula), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Luan, J. (Jian'An), Mägi, R. (Reedik), Mahajan, A. (Anubha), Mangino, M. (Massimo), Medina-Gomez, M.C. (Carolina), Monda, K.L. (Keri), Nolte, I.M. (Ilja), Perusse, L. (Louis), Prokopenko, I. (Inga), Qi, L. (Lu), Rose, L.M. (Lynda), Salvi, E. (Erika), Smith, M.T. (Megan T.), Snieder, H. (Harold), Standáková, A. (Alena), Ju Sung, Y. (Yun), Tachmazidou, I. (Ioanna), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Harst, P. (Pim) van der, Walker, R.W. (Ryan W.), Wang, S.R. (Sophie), Wild, S.H. (Sarah), Willems, S.M. (Sara), Wong, A. (Andrew), Zhang, W. (Weihua), Albrecht, E. (Eva), Couto-Alves, A. (Alexessander), Bakker, S.J.L. (Stephan), Barlassina, C. (Cristina), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bellis, C. (Claire), Bergman, R.N. (Richard N.), Bergmann, S.M. (Sven), Blangero, J. (John), Blüher, M. (Matthias), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan R.), Bruinenberg, M. (M.), Campbell, H. (Harry), Chen, Y.-D.I. (Yii-Der Ida), Chiang, C.W.K. (Charleston W. K.), Chines, P.S. (Peter), Collins, F.S. (Francis), Cucca, F. (Fracensco), Cupples, L.A. (Adrienne), D'avila, F. (Francesca), Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Dimitriou, M. (Maria), Döring, A. (Angela), Hagen, K. (Knut), Farmaki, A.-E. (Aliki-Eleni), Farrall, M. (Martin), Ferreira, T. (Teresa), Fischer, K. (Krista), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gjesing, A.P. (Anette), Glorioso, N. (Nicola), Graff, M.J. (Maud J.L.), Grallert, H. (Harald), Grarup, N. (Niels), Gräßler, J. (Jürgen), Grewal, J. (Jagvir), Hamsten, A. (Anders), Harder, M.N. (Marie Neergaard), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Havulinna, A.S. (Aki), Heliovaara, M. (Markku), Hillege, H.L. (Hans), Hofman, A. (Albert), Holmen, O.L. (Oddgeir), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Hui, J. (Jennie), Husemoen, L.L.N. (Lise Lotte), Hysi, P.G. (Pirro), Isaacs, A.J. (Aaron), Ittermann, T. (Till), Jalilzadeh, S. (Shapour), James, A. (Alan), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Marie Justesen, J. (Johanne), Justice, A.E. (Anne), Kähönen, M. (Mika), Karaleftheri, M. (Maria), Tee Khaw, K. (Kay), Keinanen-Kiukaanniemi, S. (Sirkka), Kinnunen, L. (Leena), Knekt, P., Koistinen, H. (Heikki), Kolcic, I. (Ivana), Kooner, I.K. (Ishminder K.), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyriakou, T. (Theodosios), Laitinen, T. (Tomi), Langenberg, C. (Claudia), Lewin, A. (Alex), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia), Lindström, J. (Jaana), Linneberg, A. (Allan), Lorbeer, R. (Roberto), Lorentzon, M. (Mattias), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Manunta, P. (Paolo), Leach, I.M. (Irene Mateo), McArdle, W.L. (Wendy), Mcknight, B. (Barbara), Mohlke, K.L. (Karen), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Montasser, M.E. (May E.), Morris, A.P. (Andrew), Müller, G. (Gabriele), Musk, A.W. (Arthur W.), Narisu, N. (Narisu), Ong, K.K. (Ken K.), Oostra, B.A. (Ben), Osmond, C. (Clive), Palotie, A. (Aarno), Pankow, J.S. (James), Paternoster, L. (Lavinia), Penninx, B.W.J.H. (Brenda), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C., Rayner, N.W. (Nigel William), Ribel-Madsen, R. (Rasmus), Rice, T.K. (Treva K.), Richards, M. (Marcus), Ridker, P.M. (Paul), Rivadeneira Ramirez, F. (Fernando), Ryan, K.A. (Kathy A.), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Sebert, S. (Sylvain), Southam, L. (Lorraine), Sparsø, T. (Thomas), Steinthorsdottir, V. (Valgerdur), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Swertz, M. (Morris), Swift, A.J. (Amy), Tönjes, A. (Anke), Tsafantakis, E. (Emmanouil), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vandenput, L. (Liesbeth), Vartiainen, E. (Erkki), Venturini, C. (Cristina), Verweij, N. (Niek), Viikari, J. (Jorma), Vitart, V. (Veronique), Vohl, M.-C. (Marie-Claude), Vonk, J.M. (Judith), Waeber, G. (Gérard), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilsgaard, T. (Tom), Winkler, T.W. (Thomas W.), Wright, A.F. (Alan), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Chambers, J.C. (John), Chasman, D.I. (Daniel), Cusi, D. (Daniele), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Hansen, T. (T.), Hicks, A.A. (Andrew), Hu, F. (Frank), Hveem, K. (Kristian), Jarvelin, M.-R. (Marjo-Riitta), Kajantie, E. (Eero), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Kuusisto, J. (Johanna), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Metspalu, A. (Andres), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Palmer, L.J. (Lyle J.), Pedersen, O. (Oluf), Perola, M. (Markus), Peters, A. (Annette), Psaty, B.M. (Bruce), Puolijoki, H. (Hannu), Rauramaa, R. (Rainer), Rudan, I. (Igor), Salomaa, V. (Veikko), Schwarz, P.E.H. (Peter), Shudiner, A.R. (Alan R.), Smit, J.H. (Jan), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Stumvoll, M. (Michael), Tremblay, A. (Angelo), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Völker, U. (Uwe), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Zeggini, E. (Eleftheria), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Duijn, C.M. (Cornelia) van, Fox, C.S. (Caroline), Groop, L. (Leif), Heid, I.M. (Iris), Hunter, D.J. (David J.), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark), North, K.E. (Kari), O´Connell, J.R., Schlessinger, D. (David), Thorsteinsdottir, U. (Unnur), Strachan, D.P. (David), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Müller-Nurasyid, M. (Martina), Loos, R.J.F. (Ruth), Ried, J.S. (Janina), Jeff, J. (Janina), Chu, A.Y. (Audrey Y), Bragg-Gresham, J.L. (Jennifer L.), Dongen, J. (Jenny) van, Huffman, J.E. (Jennifer), Ahluwalia, T.S. (Tarunveer Singh), Cadby, G. (Gemma), Eklund, N. (Niina), Eriksson, J. (Joel), Esko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Gorski, M. (Mathias), Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Jackson, A.U. (Anne), Jokinen, E. (Eero), Kanoni, S. (Stavroula), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Luan, J. (Jian'An), Mägi, R. (Reedik), Mahajan, A. (Anubha), Mangino, M. (Massimo), Medina-Gomez, M.C. (Carolina), Monda, K.L. (Keri), Nolte, I.M. (Ilja), Perusse, L. (Louis), Prokopenko, I. (Inga), Qi, L. (Lu), Rose, L.M. (Lynda), Salvi, E. (Erika), Smith, M.T. (Megan T.), Snieder, H. (Harold), Standáková, A. (Alena), Ju Sung, Y. (Yun), Tachmazidou, I. (Ioanna), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Harst, P. (Pim) van der, Walker, R.W. (Ryan W.), Wang, S.R. (Sophie), Wild, S.H. (Sarah), Willems, S.M. (Sara), Wong, A. (Andrew), Zhang, W. (Weihua), Albrecht, E. (Eva), Couto-Alves, A. (Alexessander), Bakker, S.J.L. (Stephan), Barlassina, C. (Cristina), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bellis, C. (Claire), Bergman, R.N. (Richard N.), Bergmann, S.M. (Sven), Blangero, J. (John), Blüher, M. (Matthias), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan R.), Bruinenberg, M. (M.), Campbell, H. (Harry), Chen, Y.-D.I. (Yii-Der Ida), Chiang, C.W.K. (Charleston W. K.), Chines, P.S. (Peter), Collins, F.S. (Francis), Cucca, F. (Fracensco), Cupples, L.A. (Adrienne), D'avila, F. (Francesca), Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Dimitriou, M. (Maria), Döring, A. (Angela), Hagen, K. (Knut), Farmaki, A.-E. (Aliki-Eleni), Farrall, M. (Martin), Ferreira, T. (Teresa), Fischer, K. (Krista), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gjesing, A.P. (Anette), Glorioso, N. (Nicola), Graff, M.J. (Maud J.L.), Grallert, H. (Harald), Grarup, N. (Niels), Gräßler, J. (Jürgen), Grewal, J. (Jagvir), Hamsten, A. (Anders), Harder, M.N. (Marie Neergaard), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Havulinna, A.S. (Aki), Heliovaara, M. (Markku), Hillege, H.L. (Hans), Hofman, A. (Albert), Holmen, O.L. (Oddgeir), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Hui, J. (Jennie), Husemoen, L.L.N. (Lise Lotte), Hysi, P.G. (Pirro), Isaacs, A.J. (Aaron), Ittermann, T. (Till), Jalilzadeh, S. (Shapour), James, A. (Alan), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Marie Justesen, J. (Johanne), Justice, A.E. (Anne), Kähönen, M. (Mika), Karaleftheri, M. (Maria), Tee Khaw, K. (Kay), Keinanen-Kiukaanniemi, S. (Sirkka), Kinnunen, L. (Leena), Knekt, P., Koistinen, H. (Heikki), Kolcic, I. (Ivana), Kooner, I.K. (Ishminder K.), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyriakou, T. (Theodosios), Laitinen, T. (Tomi), Langenberg, C. (Claudia), Lewin, A. (Alex), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia), Lindström, J. (Jaana), Linneberg, A. (Allan), Lorbeer, R. (Roberto), Lorentzon, M. (Mattias), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Manunta, P. (Paolo), Leach, I.M. (Irene Mateo), McArdle, W.L. (Wendy), Mcknight, B. (Barbara), Mohlke, K.L. (Karen), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Montasser, M.E. (May E.), Morris, A.P. (Andrew), Müller, G. (Gabriele), Musk, A.W. (Arthur W.), Narisu, N. (Narisu), Ong, K.K. (Ken K.), Oostra, B.A. (Ben), Osmond, C. (Clive), Palotie, A. (Aarno), Pankow, J.S. (James), Paternoster, L. (Lavinia), Penninx, B.W.J.H. (Brenda), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C., Rayner, N.W. (Nigel William), Ribel-Madsen, R. (Rasmus), Rice, T.K. (Treva K.), Richards, M. (Marcus), Ridker, P.M. (Paul), Rivadeneira Ramirez, F. (Fernando), Ryan, K.A. (Kathy A.), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Sebert, S. (Sylvain), Southam, L. (Lorraine), Sparsø, T. (Thomas), Steinthorsdottir, V. (Valgerdur), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Swertz, M. (Morris), Swift, A.J. (Amy), Tönjes, A. (Anke), Tsafantakis, E. (Emmanouil), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vandenput, L. (Liesbeth), Vartiainen, E. (Erkki), Venturini, C. (Cristina), Verweij, N. (Niek), Viikari, J. (Jorma), Vitart, V. (Veronique), Vohl, M.-C. (Marie-Claude), Vonk, J.M. (Judith), Waeber, G. (Gérard), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilsgaard, T. (Tom), Winkler, T.W. (Thomas W.), Wright, A.F. (Alan), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Chambers, J.C. (John), Chasman, D.I. (Daniel), Cusi, D. (Daniele), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Hansen, T. (T.), Hicks, A.A. (Andrew), Hu, F. (Frank), Hveem, K. (Kristian), Jarvelin, M.-R. (Marjo-Riitta), Kajantie, E. (Eero), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Kuusisto, J. (Johanna), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Metspalu, A. (Andres), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Palmer, L.J. (Lyle J.), Pedersen, O. (Oluf), Perola, M. (Markus), Peters, A. (Annette), Psaty, B.M. (Bruce), Puolijoki, H. (Hannu), Rauramaa, R. (Rainer), Rudan, I. (Igor), Salomaa, V. (Veikko), Schwarz, P.E.H. (Peter), Shudiner, A.R. (Alan R.), Smit, J.H. (Jan), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Stumvoll, M. (Michael), Tremblay, A. (Angelo), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Völker, U. (Uwe), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Zeggini, E. (Eleftheria), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Duijn, C.M. (Cornelia) van, Fox, C.S. (Caroline), Groop, L. (Leif), Heid, I.M. (Iris), Hunter, D.J. (David J.), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark), North, K.E. (Kari), O´Connell, J.R., Schlessinger, D. (David), Thorsteinsdottir, U. (Unnur), Strachan, D.P. (David), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Müller-Nurasyid, M. (Martina), and Loos, R.J.F. (Ruth)
Abstract: Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
Published: 2016
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10. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author: Ried, J. S. (Janina S.), Jeff, J. M. (Janina M.), Chu, A. Y. (Audrey Y.), Bragg-Gresham, J. L. (Jennifer L.), van Dongen, J. (Jenny), Huffman, J. E. (Jennifer E.), Ahluwalia, T. S. (Tarunveer S.), Cadby, G. (Gemma), Eklund, N. (Niina), Eriksson, J. (Joel), Esko, T. (Tonu), Feitosa, M. F. (Mary F.), Goel, A. (Anuj), Gorski, M. (Mathias), Hayward, C. (Caroline), Heard-Costa, N. L. (Nancy L.), Jackson, A. U. (Anne U.), Jokinen, E. (Eero), Kanoni, S. (Stavroula), Kristiansson, K. (Kati), Kutalik, Z. (Zoltan), Lahti, J. (Jari), Luan, J. (Jian'an), Maegi, R. (Reedik), Mahajan, A. (Anubha), Mangino, M. (Massimo), Medina-Gomez, C. (Carolina), Monda, K. L. (Keri L.), Nolte, I. M. (Ilja M.), Perusse, L. (Louis), Prokopenko, I. (Inga), Qi, L. (Lu), Rose, L. M. (Lynda M.), Salvi, E. (Erika), Smith, M. T. (Megan T.), Snieder, H. (Harold), Stancakova, A. (Alena), Sung, Y. J. (Yun Ju), Tachmazidou, I. (Ioanna), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), van der Harst, P. (Pim), Walker, R. W. (Ryan W.), Wang, S. R. (Sophie R.), Wild, S. H. (Sarah H.), Willems, S. M. (Sara M.), Wong, A. (Andrew), Zhang, W. (Weihua), Albrecht, E. (Eva), Alves, A. C. (Alexessander Couto), Bakker, S. J. (Stephan J. L.), Barlassina, C. (Cristina), Bartz, T. M. (Traci M.), Beilby, J. (John), Bellis, C. (Claire), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Blangero, J. (John), Blueher, M. (Matthias), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bruinenberg, M. (Marcel), Campbell, H. (Harry), Chen, Y. I. (Yii-Der Ida), Chiang, C. W. (Charleston W. K.), Chines, P. S. (Peter S.), Collins, F. S. (Francis S.), Cucca, F. (Fracensco), Cupples, L. A. (L. Adrienne), D'Avila, F. (Francesca), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Dimitriou, M. (Maria), Doering, A. (Angela), Eriksson, J. G. (Johan G.), Farmaki, A.-E. (Aliki-Eleni), Farrall, M. (Martin), Ferreira, T. (Teresa), Fischer, K. (Krista), Forouhi, N. G. (Nita G.), Friedrich, N. (Nele), Gjesing, A. P. (Anette Prior), Glorioso, N. (Nicola), Graff, M. (Mariaelisa), Grallert, H. (Harald), Grarup, N. (Niels), Graessler, J. (Juergen), Grewal, J. (Jagvir), Hamsten, A. (Anders), Harder, M. N. (Marie Neergaard), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nicholas), Hattersley, A. T. (Andrew Tym), Havulinna, A. S. (Aki S.), Heliovaara, M. (Markku), Hillege, H. (Hans), Hofman, A. (Albert), Holmen, O. (Oddgeir), Homuth, G. (Georg), Hottenga, J.-J. (Jouke-Jan), Hui, J. (Jennie), Husemoen, L. L. (Lise Lotte), Hysi, P. G. (Pirro G.), Isaacs, A. (Aaron), Ittermann, T. (Till), Jalilzadeh, S. (Shapour), James, A. L. (Alan L.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Justesen, J. M. (Johanne Marie), Justice, A. E. (Anne E.), Kahonen, M. (Mika), Karaleftheri, M. (Maria), Khaw, K. T. (Kay Tee), Keinänen-Kiukaanniemi, S. M. (Sirkka M.), Kinnunen, L. (Leena), Knekt, P. B. (Paul B.), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kooner, I. K. (Ishminder K.), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyriakou, T. (Theodosios), Laitinen, T. (Tomi), Langenberg, C. (Claudia), Lewin, A. M. (Alexandra M.), Lichtner, P. (Peter), Lindgren, C. M. (Cecilia M.), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Lorbeer, R. (Roberto), Lorentzon, M. (Mattias), Luben, R. (Robert), Lyssenko, V. (Valeriya), Mannisto, S. (Satu), Manunta, P. (Paolo), Leach, I. M. (Irene Mateo), McArdle, W. L. (Wendy L.), Mcknight, B. (Barbara), Mohlke, K. L. (Karen L.), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Montasser, M. E. (May E.), Morris, A. P. (Andrew P.), Mueller, G. (Gabriele), Musk, A. W. (Arthur W.), Narisu, N. (Narisu), Ong, K. K. (Ken K.), Oostra, B. A. (Ben A.), Osmond, C. (Clive), Palotie, A. (Aarno), Pankow, J. S. (James S.), Paternoster, L. (Lavinia), Penninx, B. W. (Brenda W.), Pichler, I. (Irene), Pilia, M. G. (Maria G.), Polasek, O. (Ozren), Pramstaller, P. P. (Peter P.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rayner, N. W. (Nigel W.), Ribel-Madsen, R. (Rasmus), Rice, T. K. (Treva K.), Richards, M. (Marcus), Ridker, P. M. (Paul M.), Rivadeneira, F. (Fernando), Ryan, K. A. (Kathy A.), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Scholtens, S. (Salome), Scott, R. A. (Robert A.), Sebert, S. (Sylvain), Southam, L. (Lorraine), Sparso, T. H. (Thomas Hempel), Steinthorsdottir, V. (Valgerdur), Stirrups, K. (Kathleen), Stolk, R. P. (Ronald P.), Strauch, K. (Konstantin), Stringham, H. M. (Heather M.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Toenjes, A. (Anke), Tsafantakis, E. (Emmanouil), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vandenput, L. (Liesbeth), Vartiainen, E. (Erkki), Venturini, C. (Cristina), Verweij, N. (Niek), Viikari, J. S. (Jorma S.), Vitart, V. (Veronique), Vohl, M.-C. (Marie-Claude), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Widen, E. (Elisabeth), Willemsen, G. (Gonneke), Wilsgaard, T. (Tom), Winkler, T. W. (Thomas W.), Wright, A. F. (Alan F.), Yerges-Armstrong, L. M. (Laura M.), Zhao, J. H. (Jing Hua), Zillikens, M. C. (M. Carola), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Cusi, D. (Daniele), Gansevoort, R. T. (Ron T.), Gieger, C. (Christian), Hansen, T. (Torben), Hicks, A. A. (Andrew A.), Hu, F. (Frank), Hveem, K. (Kristian), Jarvelin, M.-R. (Marjo-Riitta), Kajantie, E. (Eero), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Kuusisto, J. (Johanna), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Lehtimaeki, T. (Terho), Metspalu, A. (Andres), Njolstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A. J. (Albertine J.), Palmer, L. J. (Lyle J.), Pedersen, O. (Oluf), Perola, M. (Markus), Peters, A. (Annette), Psaty, B. M. (Bruce M.), Puolijoki, H. (Hannu), Rauramaa, R. (Rainer), Rudan, I. (Igor), Salomaa, V. (Veikko), Schwarz, P. E. (Peter E. H.), Shudiner, A. R. (Alan R.), Smit, J. H. (Jan H.), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Timothy D.), Stefansson, K. (Kari), Stumvoll, M. (Michael), Tremblay, A. (Angelo), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Voelker, U. (Uwe), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Watkins, H. (Hugh), Wilson, J. F. (James F.), Zeggini, E. (Eleftheria), Abecasis, G. R. (Goncalo R.), Boehnke, M. (Michael), Borecki, I. B. (Ingrid B.), Deloukas, P. (Panos), van Duijn, C. M. (Cornelia M.), Fox, C. (Caroline), Groop, L. C. (Leif C.), Heid, I. M. (Iris M.), Hunter, D. J. (David J.), Kaplan, R. C. (Robert C.), McCarthy, M. I. (Mark I.), North, K. E. (Kari E.), O'Connell, J. R. (Jeffrey R.), Schlessinger, D. (David), Thorsteinsdottir, U. (Unnur), Strachan, D. P. (David P.), Frayling, T. (Timothy), Hirschhorn, J. N. (Joel N.), Mueller-Nurasyid, M. (Martina), Loos, R. J. (Ruth J. F.), Ried, J. S. (Janina S.), Jeff, J. M. (Janina M.), Chu, A. Y. (Audrey Y.), Bragg-Gresham, J. L. (Jennifer L.), van Dongen, J. (Jenny), Huffman, J. E. (Jennifer E.), Ahluwalia, T. S. (Tarunveer S.), Cadby, G. (Gemma), Eklund, N. (Niina), Eriksson, J. (Joel), Esko, T. (Tonu), Feitosa, M. F. (Mary F.), Goel, A. (Anuj), Gorski, M. (Mathias), Hayward, C. (Caroline), Heard-Costa, N. L. (Nancy L.), Jackson, A. U. (Anne U.), Jokinen, E. (Eero), Kanoni, S. (Stavroula), Kristiansson, K. (Kati), Kutalik, Z. (Zoltan), Lahti, J. (Jari), Luan, J. (Jian'an), Maegi, R. (Reedik), Mahajan, A. (Anubha), Mangino, M. (Massimo), Medina-Gomez, C. (Carolina), Monda, K. L. (Keri L.), Nolte, I. M. (Ilja M.), Perusse, L. (Louis), Prokopenko, I. (Inga), Qi, L. (Lu), Rose, L. M. (Lynda M.), Salvi, E. (Erika), Smith, M. T. (Megan T.), Snieder, H. (Harold), Stancakova, A. (Alena), Sung, Y. J. (Yun Ju), Tachmazidou, I. (Ioanna), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), van der Harst, P. (Pim), Walker, R. W. (Ryan W.), Wang, S. R. (Sophie R.), Wild, S. H. (Sarah H.), Willems, S. M. (Sara M.), Wong, A. (Andrew), Zhang, W. (Weihua), Albrecht, E. (Eva), Alves, A. C. (Alexessander Couto), Bakker, S. J. (Stephan J. L.), Barlassina, C. (Cristina), Bartz, T. M. (Traci M.), Beilby, J. (John), Bellis, C. (Claire), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Blangero, J. (John), Blueher, M. (Matthias), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bruinenberg, M. (Marcel), Campbell, H. (Harry), Chen, Y. I. (Yii-Der Ida), Chiang, C. W. (Charleston W. K.), Chines, P. S. (Peter S.), Collins, F. S. (Francis S.), Cucca, F. (Fracensco), Cupples, L. A. (L. Adrienne), D'Avila, F. (Francesca), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Dimitriou, M. (Maria), Doering, A. (Angela), Eriksson, J. G. (Johan G.), Farmaki, A.-E. (Aliki-Eleni), Farrall, M. (Martin), Ferreira, T. (Teresa), Fischer, K. (Krista), Forouhi, N. G. (Nita G.), Friedrich, N. (Nele), Gjesing, A. P. (Anette Prior), Glorioso, N. (Nicola), Graff, M. (Mariaelisa), Grallert, H. (Harald), Grarup, N. (Niels), Graessler, J. (Juergen), Grewal, J. (Jagvir), Hamsten, A. (Anders), Harder, M. N. (Marie Neergaard), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nicholas), Hattersley, A. T. (Andrew Tym), Havulinna, A. S. (Aki S.), Heliovaara, M. (Markku), Hillege, H. (Hans), Hofman, A. (Albert), Holmen, O. (Oddgeir), Homuth, G. (Georg), Hottenga, J.-J. (Jouke-Jan), Hui, J. (Jennie), Husemoen, L. L. (Lise Lotte), Hysi, P. G. (Pirro G.), Isaacs, A. (Aaron), Ittermann, T. (Till), Jalilzadeh, S. (Shapour), James, A. L. (Alan L.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Justesen, J. M. (Johanne Marie), Justice, A. E. (Anne E.), Kahonen, M. (Mika), Karaleftheri, M. (Maria), Khaw, K. T. (Kay Tee), Keinänen-Kiukaanniemi, S. M. (Sirkka M.), Kinnunen, L. (Leena), Knekt, P. B. (Paul B.), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kooner, I. K. (Ishminder K.), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyriakou, T. (Theodosios), Laitinen, T. (Tomi), Langenberg, C. (Claudia), Lewin, A. M. (Alexandra M.), Lichtner, P. (Peter), Lindgren, C. M. (Cecilia M.), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Lorbeer, R. (Roberto), Lorentzon, M. (Mattias), Luben, R. (Robert), Lyssenko, V. (Valeriya), Mannisto, S. (Satu), Manunta, P. (Paolo), Leach, I. M. (Irene Mateo), McArdle, W. L. (Wendy L.), Mcknight, B. (Barbara), Mohlke, K. L. (Karen L.), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Montasser, M. E. (May E.), Morris, A. P. (Andrew P.), Mueller, G. (Gabriele), Musk, A. W. (Arthur W.), Narisu, N. (Narisu), Ong, K. K. (Ken K.), Oostra, B. A. (Ben A.), Osmond, C. (Clive), Palotie, A. (Aarno), Pankow, J. S. (James S.), Paternoster, L. (Lavinia), Penninx, B. W. (Brenda W.), Pichler, I. (Irene), Pilia, M. G. (Maria G.), Polasek, O. (Ozren), Pramstaller, P. P. (Peter P.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rayner, N. W. (Nigel W.), Ribel-Madsen, R. (Rasmus), Rice, T. K. (Treva K.), Richards, M. (Marcus), Ridker, P. M. (Paul M.), Rivadeneira, F. (Fernando), Ryan, K. A. (Kathy A.), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Scholtens, S. (Salome), Scott, R. A. (Robert A.), Sebert, S. (Sylvain), Southam, L. (Lorraine), Sparso, T. H. (Thomas Hempel), Steinthorsdottir, V. (Valgerdur), Stirrups, K. (Kathleen), Stolk, R. P. (Ronald P.), Strauch, K. (Konstantin), Stringham, H. M. (Heather M.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Toenjes, A. (Anke), Tsafantakis, E. (Emmanouil), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vandenput, L. (Liesbeth), Vartiainen, E. (Erkki), Venturini, C. (Cristina), Verweij, N. (Niek), Viikari, J. S. (Jorma S.), Vitart, V. (Veronique), Vohl, M.-C. (Marie-Claude), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Widen, E. (Elisabeth), Willemsen, G. (Gonneke), Wilsgaard, T. (Tom), Winkler, T. W. (Thomas W.), Wright, A. F. (Alan F.), Yerges-Armstrong, L. M. (Laura M.), Zhao, J. H. (Jing Hua), Zillikens, M. C. (M. Carola), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Cusi, D. (Daniele), Gansevoort, R. T. (Ron T.), Gieger, C. (Christian), Hansen, T. (Torben), Hicks, A. A. (Andrew A.), Hu, F. (Frank), Hveem, K. (Kristian), Jarvelin, M.-R. (Marjo-Riitta), Kajantie, E. (Eero), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Kuusisto, J. (Johanna), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Lehtimaeki, T. (Terho), Metspalu, A. (Andres), Njolstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A. J. (Albertine J.), Palmer, L. J. (Lyle J.), Pedersen, O. (Oluf), Perola, M. (Markus), Peters, A. (Annette), Psaty, B. M. (Bruce M.), Puolijoki, H. (Hannu), Rauramaa, R. (Rainer), Rudan, I. (Igor), Salomaa, V. (Veikko), Schwarz, P. E. (Peter E. H.), Shudiner, A. R. (Alan R.), Smit, J. H. (Jan H.), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Timothy D.), Stefansson, K. (Kari), Stumvoll, M. (Michael), Tremblay, A. (Angelo), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Voelker, U. (Uwe), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Watkins, H. (Hugh), Wilson, J. F. (James F.), Zeggini, E. (Eleftheria), Abecasis, G. R. (Goncalo R.), Boehnke, M. (Michael), Borecki, I. B. (Ingrid B.), Deloukas, P. (Panos), van Duijn, C. M. (Cornelia M.), Fox, C. (Caroline), Groop, L. C. (Leif C.), Heid, I. M. (Iris M.), Hunter, D. J. (David J.), Kaplan, R. C. (Robert C.), McCarthy, M. I. (Mark I.), North, K. E. (Kari E.), O'Connell, J. R. (Jeffrey R.), Schlessinger, D. (David), Thorsteinsdottir, U. (Unnur), Strachan, D. P. (David P.), Frayling, T. (Timothy), Hirschhorn, J. N. (Joel N.), Mueller-Nurasyid, M. (Martina), and Loos, R. J. (Ruth J. F.)
Abstract: Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
Published: 2016

11. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Ehret, G. B. (Georg B.), Ferreira, T. (Teresa), Chasman, D. I. (Daniel I.), Jackson, A. U. (Anne U.), Schmidt, E. M. (Ellen M.), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'an), Donnelly, L. A. (Louise A.), Kanoni, S. (Stavroula), Petersen, A. -. (Ann -Kristin), Pihurl, V. (Vasyl), Strawbridge, R. J. (Rona J.), Shungin, D. (Dmitry), Hughes, M. F. (Maria F.), Meirelles, O. (Osorio), Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M. E. (Marcus E.), Guo, X. (Xiuqing), Lyytikainen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Nidas), Nolte, I. M. (Ilja M.), Magnusson, P. K. (Patrik K.), Salfati, E. L. (Elias L.), Rallidis, L. S. (Loukianos S.), Theusch, E. (Elizabeth), Smith, A. J. (Andrew J. P.), Folkersen, L. (Lasse), Witkowska, K. (Kate), Pers, T. H. (Tune H.), Joehanes, R. (Roby), Kim, S. K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R. (Rick), Johnson, A. D. (Andrew D.), Warren, H. (Helen), Kim, Y. J. (Young Jin), Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. O. (Bamidele O.), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L. S. (Linda S.), Amin, N. (Najaf), Arkingl, D. E. (Dan E.), Axelsson, T. (Tomas), Baldassarre, D. (Damian), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M. R. (Michael R.), Barroso, I. (Ines), Bevan, S. (Stephen), Bis, J. C. (Joshua C.), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Boomsma, D. I. (Dorret I.), Bornstein, S. R. (Stefan R.), Brown, M. J. (Morris J.), Burnier, M. (Michel), Cabrera, C. P. (Claudia P.), Chambers, J. C. (John C.), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P. S. (Peter S.), Chung, R.-H. (Ren-Hua), Collins, F. S. (Francis S.), Connell, J. M. (John M.), Doring, A. (Angela), Dallongeville, J. (Jean), Danesh, J. (John), de Faire, U. (Ulf), Delgado, G. (Graciela), Dominiczak, A. F. (Anna F.), Doney, A. S. (Alex S. F.), Drenos, F. (Fotios), Edkins, S. (Sarah), Eicher, J. D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tonu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fai, T. (Tove), Farra, M. (Martin), Felixl, J. F. (Janine F.), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschinil, N. (Nora), Franco, O. H. (Oscar H.), Franco-Cereceda, A. (Anders), Fraser, R. M. (Ross M.), Ganesh, S. K. (Santhi K.), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goe, A. (Anuj), Goodall, A. H. (Alison H.), Goodarzi, M. (Mark), Gorski, M. (Mathias), Grassler, J. (Jurgen), Groves, C. J. (Christopher J.), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Goran), Hartikainen, A.-L. (Anna-Liisa), Hassinen, M. (Maija), Havulinna, A. S. (Aki S.), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.-H. (Karl-Heinz), Hicks, A. A. (Andrew A.), Hingorani, A. D. (Aroon D.), Hirschhorn, J. N. (Joel N.), Hofmanl, A. (Albert), Holmen, J. (Jostein), Holmen, O. L. (Oddgeir Lingaas), Hottenga, J.-J. (Jouke-Jan), Howard, P. (Phil), Hsiung, C. A. (Chao A.), Hunt, S. C. (Steven C.), Ikram, M. A. (M. Arfan), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R. A. (Richard A.), Kahonen, M. (Mika), Kang, H. M. (Hyun Min), Kathiresan, S. (Sekar), Keating, B. J. (Brendan J.), Khaw, K.-T. (Kay-Tee), Kim, Y. K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J. S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R. M. (Ronald M.), Kuh, D. (Diana), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Lee, N. R. (Nanette R.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindstrom, J. (Jaana), Lobbens, S. (Stephane), Mannisto, S. (Satu), Muller, G. (Gabriele), Muller-Nurasyid, M. (Martina), Mach, F. (Francois), Markus, H. S. (Hugh S.), Marouli, E. (Eirini), McCarthy, M. I. (Mark I.), McKenzie, C. A. (Colin A.), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M. E. (May E.), Morris, A. D. (Andrew D.), Morrison, A. C. (Alanna C.), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C. J. (Christopher J.), O'Reilly, P. F. (Paul F.), Ong, K. K. (Ken K.), Paccaud, F. (Fred), Palmer, C. D. (Cameron D.), Parsa, A. (Afshin), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W.), Perola, M. (Markus), Peters, A. (Annette), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Psaty, B. M. (Bruce M.), Quertermous, T. (Thomas), Rao, D. C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N. W. (N. William), Renstrom, F. (Frida), Rettig, R. (Rainer), Rice, K. M. (Kenneth M.), Roberts, R. (Robert), Rose, L. M. (Lynda M.), Rossouw, J. (Jacques), Samani, N. J. (Nilesh J.), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W. H. (Wayne H-H), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smit, J. H. (Johannes H.), Smith, A. V. (Albert V.), Sosa, M. X. (Maria X.), Spector, T. D. (Tim D.), Stancakova, A. (Alena), Stanton, A. V. (Alice V.), Stirrups, K. E. (Kathleen E.), Stringham, H. M. (Heather M.), Sundstrom, J. (Johan), Swift, A. J. (Amy J.), Syvanen, A.-C. (Ann-Christine), Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K. V. (Kirill V.), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M. D. (Martin D.), Tremoli, E. (Elena), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), van Duijn, C. M. (Cornelia M.), van Iperen, E. P. (Erik P. A.), Vasan, R. S. (Ramachandran S.), Verwoert, G. C. (Germaine C.), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B. F. (Benjamin F.), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L. V. (Louise V.), Wareham, N. J. (Nicholas J.), Watldns, H. (Hugh), Weder, A. B. (Alan B.), Westra, H. J. (Harm Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J. F. (James F.), Wong, T. Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jie), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R. S. (Richard S.), Mohlke, K. L. (Karen L.), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, H. J. (Hinco J.), Willer, C. J. (Cristen J.), Franke, L. (Lude), Hovingh, G. K. (G. Kees), Taylor, K. D. (Kent D.), Dedoussis, G. (George), Sever, P. (Peter), Wong, A. (Andrew), Lind, L. (Lars), Assimes, T. L. (Themistocles L.), Njolstad, I. (Inger), Schwarz, P. E. (Peter E. H.), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. J. (Mark J.), Melander, E. (E.), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimaki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), Marz, W. (Winfried), Kumar, M. (Meena), Salomaa, V. (Veikko), Chen, Y. I. (Yii-Der I.), Rotter, J. I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. G. (Edward G.), Kuulasmaa, K. (Kari), Franks, P. W. (Paul W.), Hamsten, A. (Anders), Wichmann, H.-E. (H-Erich), Palmer, C. N. (Colin N. A.), Stefansson, K. (Kari), Ridker, P. M. (Paul M.), Loos, R. J. (Ruth J. F.), Chalcravarti, A. (Aravinda), Deloukas, P. (Panos), Morris, A. P. (Andrew P.), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), Ehret, G. B. (Georg B.), Ferreira, T. (Teresa), Chasman, D. I. (Daniel I.), Jackson, A. U. (Anne U.), Schmidt, E. M. (Ellen M.), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'an), Donnelly, L. A. (Louise A.), Kanoni, S. (Stavroula), Petersen, A. -. (Ann -Kristin), Pihurl, V. (Vasyl), Strawbridge, R. J. (Rona J.), Shungin, D. (Dmitry), Hughes, M. F. (Maria F.), Meirelles, O. (Osorio), Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M. E. (Marcus E.), Guo, X. (Xiuqing), Lyytikainen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Nidas), Nolte, I. M. (Ilja M.), Magnusson, P. K. (Patrik K.), Salfati, E. L. (Elias L.), Rallidis, L. S. (Loukianos S.), Theusch, E. (Elizabeth), Smith, A. J. (Andrew J. P.), Folkersen, L. (Lasse), Witkowska, K. (Kate), Pers, T. H. (Tune H.), Joehanes, R. (Roby), Kim, S. K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R. (Rick), Johnson, A. D. (Andrew D.), Warren, H. (Helen), Kim, Y. J. (Young Jin), Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. O. (Bamidele O.), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L. S. (Linda S.), Amin, N. (Najaf), Arkingl, D. E. (Dan E.), Axelsson, T. (Tomas), Baldassarre, D. (Damian), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M. R. (Michael R.), Barroso, I. (Ines), Bevan, S. (Stephen), Bis, J. C. (Joshua C.), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Boomsma, D. I. (Dorret I.), Bornstein, S. R. (Stefan R.), Brown, M. J. (Morris J.), Burnier, M. (Michel), Cabrera, C. P. (Claudia P.), Chambers, J. C. (John C.), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P. S. (Peter S.), Chung, R.-H. (Ren-Hua), Collins, F. S. (Francis S.), Connell, J. M. (John M.), Doring, A. (Angela), Dallongeville, J. (Jean), Danesh, J. (John), de Faire, U. (Ulf), Delgado, G. (Graciela), Dominiczak, A. F. (Anna F.), Doney, A. S. (Alex S. F.), Drenos, F. (Fotios), Edkins, S. (Sarah), Eicher, J. D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tonu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fai, T. (Tove), Farra, M. (Martin), Felixl, J. F. (Janine F.), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschinil, N. (Nora), Franco, O. H. (Oscar H.), Franco-Cereceda, A. (Anders), Fraser, R. M. (Ross M.), Ganesh, S. K. (Santhi K.), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goe, A. (Anuj), Goodall, A. H. (Alison H.), Goodarzi, M. (Mark), Gorski, M. (Mathias), Grassler, J. (Jurgen), Groves, C. J. (Christopher J.), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Goran), Hartikainen, A.-L. (Anna-Liisa), Hassinen, M. (Maija), Havulinna, A. S. (Aki S.), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.-H. (Karl-Heinz), Hicks, A. A. (Andrew A.), Hingorani, A. D. (Aroon D.), Hirschhorn, J. N. (Joel N.), Hofmanl, A. (Albert), Holmen, J. (Jostein), Holmen, O. L. (Oddgeir Lingaas), Hottenga, J.-J. (Jouke-Jan), Howard, P. (Phil), Hsiung, C. A. (Chao A.), Hunt, S. C. (Steven C.), Ikram, M. A. (M. Arfan), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R. A. (Richard A.), Kahonen, M. (Mika), Kang, H. M. (Hyun Min), Kathiresan, S. (Sekar), Keating, B. J. (Brendan J.), Khaw, K.-T. (Kay-Tee), Kim, Y. K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J. S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R. M. (Ronald M.), Kuh, D. (Diana), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Lee, N. R. (Nanette R.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindstrom, J. (Jaana), Lobbens, S. (Stephane), Mannisto, S. (Satu), Muller, G. (Gabriele), Muller-Nurasyid, M. (Martina), Mach, F. (Francois), Markus, H. S. (Hugh S.), Marouli, E. (Eirini), McCarthy, M. I. (Mark I.), McKenzie, C. A. (Colin A.), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M. E. (May E.), Morris, A. D. (Andrew D.), Morrison, A. C. (Alanna C.), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C. J. (Christopher J.), O'Reilly, P. F. (Paul F.), Ong, K. K. (Ken K.), Paccaud, F. (Fred), Palmer, C. D. (Cameron D.), Parsa, A. (Afshin), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W.), Perola, M. (Markus), Peters, A. (Annette), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Psaty, B. M. (Bruce M.), Quertermous, T. (Thomas), Rao, D. C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N. W. (N. William), Renstrom, F. (Frida), Rettig, R. (Rainer), Rice, K. M. (Kenneth M.), Roberts, R. (Robert), Rose, L. M. (Lynda M.), Rossouw, J. (Jacques), Samani, N. J. (Nilesh J.), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W. H. (Wayne H-H), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smit, J. H. (Johannes H.), Smith, A. V. (Albert V.), Sosa, M. X. (Maria X.), Spector, T. D. (Tim D.), Stancakova, A. (Alena), Stanton, A. V. (Alice V.), Stirrups, K. E. (Kathleen E.), Stringham, H. M. (Heather M.), Sundstrom, J. (Johan), Swift, A. J. (Amy J.), Syvanen, A.-C. (Ann-Christine), Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K. V. (Kirill V.), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M. D. (Martin D.), Tremoli, E. (Elena), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), van Duijn, C. M. (Cornelia M.), van Iperen, E. P. (Erik P. A.), Vasan, R. S. (Ramachandran S.), Verwoert, G. C. (Germaine C.), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B. F. (Benjamin F.), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L. V. (Louise V.), Wareham, N. J. (Nicholas J.), Watldns, H. (Hugh), Weder, A. B. (Alan B.), Westra, H. J. (Harm Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J. F. (James F.), Wong, T. Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jie), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R. S. (Richard S.), Mohlke, K. L. (Karen L.), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, H. J. (Hinco J.), Willer, C. J. (Cristen J.), Franke, L. (Lude), Hovingh, G. K. (G. Kees), Taylor, K. D. (Kent D.), Dedoussis, G. (George), Sever, P. (Peter), Wong, A. (Andrew), Lind, L. (Lars), Assimes, T. L. (Themistocles L.), Njolstad, I. (Inger), Schwarz, P. E. (Peter E. H.), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. J. (Mark J.), Melander, E. (E.), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimaki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), Marz, W. (Winfried), Kumar, M. (Meena), Salomaa, V. (Veikko), Chen, Y. I. (Yii-Der I.), Rotter, J. I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. G. (Edward G.), Kuulasmaa, K. (Kari), Franks, P. W. (Paul W.), Hamsten, A. (Anders), Wichmann, H.-E. (H-Erich), Palmer, C. N. (Colin N. A.), Stefansson, K. (Kari), Ridker, P. M. (Paul M.), Loos, R. J. (Ruth J. F.), Chalcravarti, A. (Aravinda), Deloukas, P. (Panos), Morris, A. P. (Andrew P.), Newton-Cheh, C. (Christopher), and Munroe, P. B. (Patricia B.)
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure–associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure–related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Published: 2016

12. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author: Winkler, T.W. (Thomas W.), Justice, A.E. (Anne), Graff, M.J. (Maud J.L.), Barata, L. (Llilda), Feitosa, M.F. (Mary Furlan), Chu, S. (Su), Czajkowski, J. (Jacek), Esko, T. (Tõnu), Fall, M. (Magnus), Kilpeläinen, T.O. (Tuomas), Lu, Y. (Yingchang), Mägi, R. (Reedik), Mihailov, E. (Evelin), Pers, T.H. (Tune), Rüeger, S. (Sina), Teumer, A. (Alexander), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Heard-Costa, N.L. (Nancy), Karjalainen, J. (Juha), Lagou, V. (Vasiliki), Mahajan, A. (Anubha), Neinast, M.D. (Michael D.), Prokopenko, I. (Inga), Simino, J. (Jeannette), Teslovich, T.M. (Tanya M.), Jansen, R., Westra, H.J. (Harm-Jan), White, C.C. (Charles), Absher, D. (Devin), Ahluwalia, T.S. (Tarunveer Singh), Ahmad, S. (Shafqat), Albrecht, E. (Eva), Alves, A.C. (Alexessander Couto), Bragg-Gresham, J.L. (Jennifer L.), Craen, A.J. (Anton) de, Bis, J.C. (Joshua), Bonnefond, A. (Amélie), Boucher, G. (Gabrielle), Cadby, G. (Gemma), Cheng, Y.-C. (Yu-Ching), Chiang, C.W. (Charleston W K), Delgado, G., Demirkan, A. (Ayşe), Dueker, N. (Nicole), Eklund, N. (Niina), Eiriksdottir, G. (Gudny), Eriksson, J. (Joel), Feenstra, B. (Bjarke), Fischer, K. (Krista), Frau, F. (Francesca), Galesloot, T.E. (Tessel), Geller, F. (Frank), Goel, A. (Anuj), Gorski, M. (Mathias), Grammer, T.B. (Tanja), Gustafsson, S. (Stefan), Haitjema, S. (Saskia), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Jacobs, K.B. (Kevin), Johansson, A. (Åsa), Kaakinen, M. (Marika), Kleber, M.E. (Marcus), Lahti, J. (Jari), Leach, I.M. (Irene Mateo), Lehne, B. (Benjamin), Liu, Y. (Youfang), Lo, K.S., Lorentzon, M. (Mattias), Luan, J. (Jian'An), Madden, P.A. (Pamela), Mangino, M. (Massimo), McKnight, B. (Barbara), Medina-Gomez, C. (Carolina), Monda, K.L. (Keri), Montasser, M.E. (May E.), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Panoutsopoulou, K. (Kalliope), Pascoe, L. (Laura), Paternoster, L. (Lavinia), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rizzi, F. (Federica), Rose, L.M. (Lynda), Ryan, K.A. (Kathy A.), Salo, P. (Perttu), Sanna, S. (Serena), Scharnagl, H. (Hubert), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Southam, L. (Lorraine), Stancáková, A. (Alena), Steinthorsdottir, V. (Valgerdur), Strawbridge, R.J. (Rona), Sung, Y.J. (Yun Ju), Tachmazidou, I. (Ioanna), Tanaka, T. (Toshiko), Thorleifsson, G. (Gudmar), Trompet, S. (Stella), Pervjakova, N. (Natalia), Tyrer, J.P. (Jonathan), Vandenput, L. (Liesbeth), Van Der Laan, S.W. (Sander W.), Velde, N. (Nathalie) van der, Setten, J. (Jessica) van, Vliet-Ostaptchouk, J.V. (Jana) van, Verweij, N. (Niek), Vlachopoulou, E. (Efthymia), Waite, L. (Lindsay), Wang, S.R. (Sophie), Wang, Z. (Zhaoming), Wild, S.H. (Sarah), Willenborg, C. (Christina), Wilson, J.F. (James), Wong, A. (Andrew), Yang, J. (Jian), Yengo, L. (Loic), Yerges-Armstrong, L.M. (Laura), Yu, L. (Lei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Andersson, E.A. (Ehm Astrid), Bakker, S.J.L. (Stephan), Baldassarre, D. (Damiano), Banasik, K. (Karina), Barcella, M. (Matteo), Barlassina, C. (Cristina), Bellis, C. (Claire), Benaglio, P. (Paola), Blangero, J. (John), Blüher, M. (Matthias), Bonnet, F. (Fabrice), Bonnycastle, L.L. (Lori), Boyd, H.A. (Heather), Bruinenberg, M. (M.), Buchman, A.S. (Aron S.), Campbell, H. (Harry), Chen, Y.D. (Y.), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Cole, J.W. (John W.), Collins, F.S. (Francis), Geus, E.J.C. (Eco) de, Groot, L.C.P.G.M. (Lisette) de, Dimitriou, M. (Maria), Duan, J. (Jubao), Enroth, S. (Stefan), Eury, E. (Elodie), Farmaki, A.-E. (Aliki-Eleni), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gejman, P.V. (Pablo), Gigante, B. (Bruna), Glorioso, N. (Nicola), Go, A.T.J.I. (Attie), Gottesman, R.F. (Rebecca), Gräßler, J. (Jürgen), Grallert, H. (Harald), Grarup, N. (Niels), Gu, Y.-M. (Yu-Mei), Broer, L. (Linda), Ham, A.C. (Annelies), Hansen, T. (T.), Harris, T.B. (Tamara), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Heath, A.C. (Andrew), Henders, A.K. (Anjali), Hernandez, D.G. (Dena), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Hui, J. (Jennie), Husemoen, L.L. (Lise L.), Hutri-Kähönen, N. (Nina), Hysi, P.G. (Pirro), Illig, T. (Thomas), Jager, P.L. (Philip) de, Jalilzadeh, S. (Shapour), Jorgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Juonala, M. (Markus), Kanoni, S. (Stavroula), Karaleftheri, M. (Maria), Khaw, K.T., Kinnunen, L. (Leena), Kittner, T. (Thomas), Koenig, W. (Wolfgang), Kolcic, I. (Ivana), Kovacs, P. (Peter), Krarup, N.T. (Nikolaj T.), Kratzer, W. (Wolfgang), Krüger, J. (Janine), Kuh, D. (Diana), Kumari, M. (Meena), Kyriakou, T. (Theodosios), Langenberg, C. (Claudia), Lannfelt, L. (Lars), Lanzani, C. (Chiara), Lotay, V. (Vaneet), Launer, L.J. (Lenore), Leander, K. (Karin), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y.-P. (Yan-Ping), Lobbens, S. (Stéphane), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Magnusson, P.K. (Patrik), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Milani, L. (Lili), Montgomery, G.W. (Grant W.), Morris, A.P. (Andrew), Narisu, N. (Narisu), Nelis, M. (Mari), Ong, K.K. (Ken), Palotie, A. (Aarno), Perusse, L. (Louis), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Pouta, A. (Anneli), Rheinberger, M. (Myriam), Ribel-Madsen, R. (Rasmus), Richards, M. (Marcus), Rice, K.M. (Kenneth), Rice, T.K. (Treva K.), Rivolta, C. (Carlo), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Scott, W.R. (William R.), Sebert, S. (Sylvain), Sengupta, S. (Sebanti), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Silveira, A. (Angela), Slagboom, P.E. (Eline), Smit, J.H. (Jan), Sparsø, T. (Thomas), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Stringham, H.M. (Heather), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Syvänen, A.C., Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tsafantakis, E. (Emmanouil), Most, P.J. (Peter) van der, Völker, U. (Uwe), Vohl, M.-C. (Marie-Claude), Vonk, J.M. (Judith), Waldenberger, M. (Melanie), Walker, R.W. (Ryan W.), Wennauer, R. (Roman), Widen, E., Willemsen, G.A.H.M. (Gonneke), Wilsgaard, T. (Tom), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Van Dijk, S. (Suzanne), Schoor, N.M. (Natasja) van, Asselbergs, F.W. (Folkert), Bakker, P.I.W. (Paul) de, Beckmann, J.S. (Jacques), Beilby, J.P. (John), Bennett, D.A. (David A.), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Böger, C.A. (Carsten), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Bottinger, E.P. (Erwin), Bouchard, C. (Claude), Chambers, J.C. (John), Chanock, S.J. (Stephen), Chasman, D.I. (Daniel), Cucca, F. (Francesco), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evans, D., Faire, U. (Ulf) de, Farrall, M. (Martin), Ferrucci, L. (Luigi), Ford, I. (Ian), Franke, L. (Lude), Franks, P.W. (Paul), Froguel, P. (Philippe), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hall, P. (Per), Hamsten, A. (Anders), Harst, P. (Pim) van der, Hayward, C. (Caroline), Heliovaara, M. (Markku), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hofman, A. (Albert), Hu, F. (Frank), Huikuri, H.V. (Heikki), Hveem, K. (Kristian), James, A. (Alan), Jordan, J.M. (Joanne M.), Jula, A. (Antti), Kähönen, M. (Mika), Kajantie, E. (Eero), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kivimaki, M. (Mika), Knekt, P., Koistinen, H. (Heikki), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kuusisto, J. (Johanna), Maerz, W. (Winfried), Martin, N.G. (Nicholas), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Levinson, D.F. (Douglas), Kao, W.H.L. (Wen), Lokki, M.L., Mäntyselkä, P. (Pekka), Melbye, M. (Mads), Metspalu, A. (Andres), Mitchell, B.D. (Braxton), Moll, F.L. (Frans), Murray, J.C. (Jeffrey), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palmer, C. (Cameron), Pankow, J.S. (James), Pasterkamp, G. (Gerard), Pedersen, N.L. (Nancy), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Quertermous, T. (Thomas), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Rioux, J.D. (John), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Saltevo, J. (Juha), Sattar, N. (Naveed), Schunkert, H. (Heribert), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Sinisalo, J. (Juha), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Staessen, J.A. (Jan A.), Stefania, B. (Bandinelli), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tardif, J.-C. (Jean-Claude), Tremoli, E. (Elena), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Verbeek, A.L.M., Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Vitart, V. (Veronique), Völzke, H. (Henry), Vollenweider, P. (Peter), Waeber, G. (Gérard), Walker, M. (Mark), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Chakravarti, A. (Aravinda), Clegg, D.J. (Deborah J.), Cupples, L.A. (Adrienne), Gordon-Larsen, P. (Penny), Jaquish, C.E. (Cashell), Rao, D.C. (Dabeeru C.), Abecasis, G.R. (Goncalo R.), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Hunter, D. (David), Ingelsson, E. (Erik), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark I.), Mohlke, K.L. (Karen), O´Connell, J.R., Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia M.), Heid, I.M. (Iris), North, K.E. (Kari), Borecki, I.B. (Ingrid), Kutalik, Z. (Zoltán), Loos, R.J.F. (Ruth), Winkler, T.W. (Thomas W.), Justice, A.E. (Anne), Graff, M.J. (Maud J.L.), Barata, L. (Llilda), Feitosa, M.F. (Mary Furlan), Chu, S. (Su), Czajkowski, J. (Jacek), Esko, T. (Tõnu), Fall, M. (Magnus), Kilpeläinen, T.O. (Tuomas), Lu, Y. (Yingchang), Mägi, R. (Reedik), Mihailov, E. (Evelin), Pers, T.H. (Tune), Rüeger, S. (Sina), Teumer, A. (Alexander), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Heard-Costa, N.L. (Nancy), Karjalainen, J. (Juha), Lagou, V. (Vasiliki), Mahajan, A. (Anubha), Neinast, M.D. (Michael D.), Prokopenko, I. (Inga), Simino, J. (Jeannette), Teslovich, T.M. (Tanya M.), Jansen, R., Westra, H.J. (Harm-Jan), White, C.C. (Charles), Absher, D. (Devin), Ahluwalia, T.S. (Tarunveer Singh), Ahmad, S. (Shafqat), Albrecht, E. (Eva), Alves, A.C. (Alexessander Couto), Bragg-Gresham, J.L. (Jennifer L.), Craen, A.J. (Anton) de, Bis, J.C. (Joshua), Bonnefond, A. (Amélie), Boucher, G. (Gabrielle), Cadby, G. (Gemma), Cheng, Y.-C. (Yu-Ching), Chiang, C.W. (Charleston W K), Delgado, G., Demirkan, A. (Ayşe), Dueker, N. (Nicole), Eklund, N. (Niina), Eiriksdottir, G. (Gudny), Eriksson, J. (Joel), Feenstra, B. (Bjarke), Fischer, K. (Krista), Frau, F. (Francesca), Galesloot, T.E. (Tessel), Geller, F. (Frank), Goel, A. (Anuj), Gorski, M. (Mathias), Grammer, T.B. (Tanja), Gustafsson, S. (Stefan), Haitjema, S. (Saskia), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Jacobs, K.B. (Kevin), Johansson, A. (Åsa), Kaakinen, M. (Marika), Kleber, M.E. (Marcus), Lahti, J. (Jari), Leach, I.M. (Irene Mateo), Lehne, B. (Benjamin), Liu, Y. (Youfang), Lo, K.S., Lorentzon, M. (Mattias), Luan, J. (Jian'An), Madden, P.A. (Pamela), Mangino, M. (Massimo), McKnight, B. (Barbara), Medina-Gomez, C. (Carolina), Monda, K.L. (Keri), Montasser, M.E. (May E.), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Panoutsopoulou, K. (Kalliope), Pascoe, L. (Laura), Paternoster, L. (Lavinia), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rizzi, F. (Federica), Rose, L.M. (Lynda), Ryan, K.A. (Kathy A.), Salo, P. (Perttu), Sanna, S. (Serena), Scharnagl, H. (Hubert), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Southam, L. (Lorraine), Stancáková, A. (Alena), Steinthorsdottir, V. (Valgerdur), Strawbridge, R.J. (Rona), Sung, Y.J. (Yun Ju), Tachmazidou, I. (Ioanna), Tanaka, T. (Toshiko), Thorleifsson, G. (Gudmar), Trompet, S. (Stella), Pervjakova, N. (Natalia), Tyrer, J.P. (Jonathan), Vandenput, L. (Liesbeth), Van Der Laan, S.W. (Sander W.), Velde, N. (Nathalie) van der, Setten, J. (Jessica) van, Vliet-Ostaptchouk, J.V. (Jana) van, Verweij, N. (Niek), Vlachopoulou, E. 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Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for B
Published: 2015
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13. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), Mohlke, K.L. (Karen), Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), and Mohlke, K.L. (Karen)
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10-8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015
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14. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Author: Berndt, S.I. (Sonja), Gustafsson, S. (Stefan), Mägi, R. (Reedik), Ganna, A. (Andrea), Wheeler, E. (Eleanor), Feitosa, M.F. (Mary Furlan), Justice, A.E. (Anne), Monda, K.L. (Keri), Croteau-Chonka, D.C. (Damien), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Ferreira, T. (Teresa), Gentilini, D. (Davide), Jackson, A.U. (Anne), Luan, J., Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Willer, C.J. (Cristen), Winkler, T.W. (Thomas), Wood, A.R. (Andrew), Workalemahu, T. (Tsegaselassie), Hu, Y.-J. (Yi-Juan), Lee, S.H. (Sang Hong), Liang, L. (Liming), Lin, D.Y. (Dan), Min, J. (Josine), Neale, B.M. (Benjamin), Thorleifsson, G. (Gudmar), Yang, J. (Jian), Albrecht, E. (Eva), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Heijer, M. (Martin) den, Eklund, N. (Niina), Fischer, K. (Krista), Goel, A. (Anuj), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jarick, I. (Ivonne), Johansson, A. (Åsa), Johnson, T. (Toby), Kanoni, S. (Stavroula), Kleber, M.E. (Marcus), König, I.R. (Inke), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lamina, C. (Claudia), Lecoeur, C. (Cécile), Li, G. (Guo), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Medina-Gomez, M.C. (Carolina), Müller-Nurasyid, M. (Martina), Ngwa, J.S., Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Pechlivanis, S. (Sonali), Perola, M. (Markus), Peters, M.J. (Marjolein), Preuss, M. (Michael), Rose, L.M. (Lynda), Shi, J. (Jianxin), Shungin, D. (Dmitry), Smith, A.V. (Davey), Strawbridge, R.J. (Rona), Surakka, I. (Ida), Teumer, A. (Alexander), Trip, M.D. (Mieke), Tyrer, J.P. (Jonathan), Vliet-Ostaptchouk, J.V. (Jana) van, Vandenput, L. (Liesbeth), Waite, L. (Lindsay), Zhao, J.H. (Jing Hua), Absher, D. (Devin), Asselbergs, F.W. (Folkert), Atalay, M. (Mustafa), Attwood, A.P. (Antony), Balmforth, A.J. (Anthony), Basart, D.C.G. (Dick), Beilby, J.P. (John), Bonnycastle, L.L. (Lori), Brambilla, P. (Paolo), Bruinenberg, M. (M.), Campbell, H. (Harry), Chasman, D.I. (Daniel), Chines, P.S. (Peter), Collins, F.S. (Francis), Connell, J. (John), Cookson, W.O. (William), Faire, U. (Ulf) de, Vegt, F. (Femmie) de, Dei, M. (Mariano), Dimitriou, M. (Maria), Edkins, T. (Ted), Estrada Gil, K. (Karol), Evans, D.M. (David), Farrall, M. (Martin), Ferrario, F. (Franco), Ferrières, J. (Jean), Franke, L. (Lude), Frau, F. (Francesca), Gejman, P.V. (Pablo), Grallert, H. (Harald), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Hall, A. (Anne), Hall, A.S. (Alistair), Hartikainen, A.L., Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Heath, A.C. (Andrew), Hebebrand, J. (Johannes), Homuth, G. (Georg), Hu, F.B. (Frank), Hunt, S.E. (Sarah), Hyppönen, E. (Elina), Iribarren, C. (Carlos), Jacobs, K.B. (Kevin), Jansson, J.-O. (John-Olov), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Kee, F. (F.), Khaw, K-T. (Kay-Tee), Kivimaki, M. (Mika), Koenig, W. (Wolfgang), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lind, L. (Lars), Lindstrom, J. (Jaana), Liu, J. (Jianjun), Liuzzi, A. (Antonio), Lokki, M.L., Lorentzon, M. (Mattias), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Manunta, P. (Paolo), Marek, D. (Diana), März, W. (Winfried), Leach, I.M. (Irene Mateo), McKnight, B. (Barbara), Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milani, L. (Lili), Montgomery, G.W. (Grant), Mooser, V. (Vincent), Mühleisen, T.W. (Thomas), Munroe, P. (Patricia), Musk, A.W. (Arthur), Narisu, N. (Narisu), Navis, G. (Gerjan), Nicholson, G. (Ggeorge), Nohr, C. (Christian), Ong, K. (Ken), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Palotie, A. (Aarno), Peden, J. (John), Pedersen, N.L. (Nancy), Peters, A. (Annette), Polasek, O. (Ozren), Pouta, A. (Anneli), Pramstaller, P.P. (Peter Paul), Prokopenko, I. (Inga), Pütter, C. (Carolin), Radhakrishnan, A. (Aparna), Raitakari, O. (Olli), Rendon, A. (Augusto), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Saaristo, T. (Timo), Sambrook, J.G. (Jennifer), Sanders, A.R. (Alan), Sanna, S. (Serena), Saramies, J. (Jouko), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Shin, S.-Y., Signorini, S. (Stefano), Sinisalo, J. (Juha), Skrobek, B. (Boris), Soranzo, N. (Nicole), Stancáková, A. (Alena), Stark, K. (Klaus), Stephens, J. (Jonathan), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Stumvoll, M. (Michael), Swift, A.J. (Amy), Theodoraki, E.V. (Eirini), Thorand, B. (Barbara), Tregouet, D.-A. (David-Alexandre), Tremoli, E. (Elena), Klauw, M.M. (Melanie) van der, Meurs, J.B.J. (Joyce) van, Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Waeber, G. (Gérard), Wang, Z. (Zhaoming), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Winkelmann, B., Witteman, J.C.M. (Jacqueline), Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Amouyel, P. (Philippe), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Cupples, L.A. (Adrienne), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Eriksson, J.G. (Johan), Franks, P.W. (Paul), Froguel, P. (Philippe), Gieger, C. (Christian), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hinney, A. (Anke), Hofman, A. (Albert), Hovingh, G.K. (Kees), Hveem, K. (Kristian), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Jöckel, K.-H. (Karl-Heinz), Keinanen-Kiukaanniemi, S. (Sirkka), Kiemeney, L.A.L.M. (Bart), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Levinson, D.F. (Douglas), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Morris, A.D. (Andrew), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ouwehand, W.H. (Willem), Palmer, C. (Cameron), Penninx, B.W.J.H. (Brenda), Power, C. (Christopher), Province, M.A. (Mike), Psaty, B.M. (Bruce), Qi, L. (Lu), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Snieder, H. (Harold), Sorensen, H.G., Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Tönjes, A. (Anke), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Vollenweider, P. (Peter), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Wilson, J.F. (James F), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C. (Craig), Frayling, T.M. (Timothy), Groop, L. (Leif), Haritunian, T. (Talin), Heid, I.M. (Iris), Hunter, D. (David), Kaplan, R.C. (Robert), Karpe, F. (Fredrik), Moffatt, M.F. (Miriam), Mohlke, K.L. (Karen), O´Connell, J.R., Pawitan, Y. (Yudi), Schadt, E.E. (Eric), Schlessinger, D. (David), Steinthorsdottir, V. (Valgerdur), Strachan, D.P. (David), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Di Blasio, A.M. (Anna Maria), Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia), Meyre, D. (David), Scherag, A. (Andre), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Loos, R.J.F. (Ruth), Ingelsson, E. (Erik), Berndt, S.I. (Sonja), Gustafsson, S. (Stefan), Mägi, R. (Reedik), Ganna, A. (Andrea), Wheeler, E. (Eleanor), Feitosa, M.F. (Mary Furlan), Justice, A.E. (Anne), Monda, K.L. (Keri), Croteau-Chonka, D.C. (Damien), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Ferreira, T. (Teresa), Gentilini, D. (Davide), Jackson, A.U. (Anne), Luan, J., Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Willer, C.J. (Cristen), Winkler, T.W. (Thomas), Wood, A.R. (Andrew), Workalemahu, T. (Tsegaselassie), Hu, Y.-J. (Yi-Juan), Lee, S.H. (Sang Hong), Liang, L. (Liming), Lin, D.Y. (Dan), Min, J. (Josine), Neale, B.M. (Benjamin), Thorleifsson, G. (Gudmar), Yang, J. (Jian), Albrecht, E. (Eva), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Heijer, M. (Martin) den, Eklund, N. (Niina), Fischer, K. (Krista), Goel, A. (Anuj), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jarick, I. (Ivonne), Johansson, A. (Åsa), Johnson, T. (Toby), Kanoni, S. (Stavroula), Kleber, M.E. (Marcus), König, I.R. (Inke), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lamina, C. (Claudia), Lecoeur, C. (Cécile), Li, G. (Guo), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Medina-Gomez, M.C. (Carolina), Müller-Nurasyid, M. (Martina), Ngwa, J.S., Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Pechlivanis, S. (Sonali), Perola, M. (Markus), Peters, M.J. (Marjolein), Preuss, M. (Michael), Rose, L.M. (Lynda), Shi, J. (Jianxin), Shungin, D. (Dmitry), Smith, A.V. (Davey), Strawbridge, R.J. (Rona), Surakka, I. (Ida), Teumer, A. (Alexander), Trip, M.D. (Mieke), Tyrer, J.P. (Jonathan), Vliet-Ostaptchouk, J.V. (Jana) van, Vandenput, L. (Liesbeth), Waite, L. (Lindsay), Zhao, J.H. (Jing Hua), Absher, D. (Devin), Asselbergs, F.W. (Folkert), Atalay, M. (Mustafa), Attwood, A.P. (Antony), Balmforth, A.J. (Anthony), Basart, D.C.G. (Dick), Beilby, J.P. (John), Bonnycastle, L.L. (Lori), Brambilla, P. (Paolo), Bruinenberg, M. (M.), Campbell, H. (Harry), Chasman, D.I. (Daniel), Chines, P.S. (Peter), Collins, F.S. (Francis), Connell, J. (John), Cookson, W.O. (William), Faire, U. (Ulf) de, Vegt, F. (Femmie) de, Dei, M. (Mariano), Dimitriou, M. (Maria), Edkins, T. (Ted), Estrada Gil, K. (Karol), Evans, D.M. (David), Farrall, M. (Martin), Ferrario, F. (Franco), Ferrières, J. (Jean), Franke, L. (Lude), Frau, F. (Francesca), Gejman, P.V. (Pablo), Grallert, H. (Harald), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Hall, A. (Anne), Hall, A.S. (Alistair), Hartikainen, A.L., Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Heath, A.C. (Andrew), Hebebrand, J. (Johannes), Homuth, G. (Georg), Hu, F.B. (Frank), Hunt, S.E. (Sarah), Hyppönen, E. (Elina), Iribarren, C. (Carlos), Jacobs, K.B. (Kevin), Jansson, J.-O. (John-Olov), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Kee, F. (F.), Khaw, K-T. (Kay-Tee), Kivimaki, M. (Mika), Koenig, W. (Wolfgang), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lind, L. (Lars), Lindstrom, J. (Jaana), Liu, J. (Jianjun), Liuzzi, A. (Antonio), Lokki, M.L., Lorentzon, M. (Mattias), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Manunta, P. (Paolo), Marek, D. (Diana), März, W. (Winfried), Leach, I.M. (Irene Mateo), McKnight, B. (Barbara), Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milani, L. (Lili), Montgomery, G.W. (Grant), Mooser, V. (Vincent), Mühleisen, T.W. (Thomas), Munroe, P. (Patricia), Musk, A.W. (Arthur), Narisu, N. (Narisu), Navis, G. (Gerjan), Nicholson, G. (Ggeorge), Nohr, C. (Christian), Ong, K. (Ken), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Palotie, A. (Aarno), Peden, J. (John), Pedersen, N.L. (Nancy), Peters, A. (Annette), Polasek, O. (Ozren), Pouta, A. (Anneli), Pramstaller, P.P. (Peter Paul), Prokopenko, I. (Inga), Pütter, C. (Carolin), Radhakrishnan, A. (Aparna), Raitakari, O. (Olli), Rendon, A. (Augusto), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Saaristo, T. (Timo), Sambrook, J.G. (Jennifer), Sanders, A.R. (Alan), Sanna, S. (Serena), Saramies, J. (Jouko), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Shin, S.-Y., Signorini, S. (Stefano), Sinisalo, J. (Juha), Skrobek, B. (Boris), Soranzo, N. (Nicole), Stancáková, A. (Alena), Stark, K. (Klaus), Stephens, J. (Jonathan), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Stumvoll, M. (Michael), Swift, A.J. (Amy), Theodoraki, E.V. (Eirini), Thorand, B. (Barbara), Tregouet, D.-A. (David-Alexandre), Tremoli, E. (Elena), Klauw, M.M. (Melanie) van der, Meurs, J.B.J. (Joyce) van, Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Waeber, G. (Gérard), Wang, Z. (Zhaoming), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Winkelmann, B., Witteman, J.C.M. (Jacqueline), Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Amouyel, P. (Philippe), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Cupples, L.A. (Adrienne), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Eriksson, J.G. (Johan), Franks, P.W. (Paul), Froguel, P. (Philippe), Gieger, C. (Christian), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hinney, A. (Anke), Hofman, A. (Albert), Hovingh, G.K. (Kees), Hveem, K. (Kristian), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Jöckel, K.-H. (Karl-Heinz), Keinanen-Kiukaanniemi, S. (Sirkka), Kiemeney, L.A.L.M. (Bart), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Levinson, D.F. (Douglas), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Morris, A.D. (Andrew), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ouwehand, W.H. (Willem), Palmer, C. (Cameron), Penninx, B.W.J.H. (Brenda), Power, C. (Christopher), Province, M.A. (Mike), Psaty, B.M. (Bruce), Qi, L. (Lu), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Snieder, H. (Harold), Sorensen, H.G., Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Tönjes, A. (Anke), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Vollenweider, P. (Peter), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Wilson, J.F. (James F), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C. (Craig), Frayling, T.M. (Timothy), Groop, L. (Leif), Haritunian, T. (Talin), Heid, I.M. (Iris), Hunter, D. (David), Kaplan, R.C. (Robert), Karpe, F. (Fredrik), Moffatt, M.F. (Miriam), Mohlke, K.L. (Karen), O´Connell, J.R., Pawitan, Y. (Yudi), Schadt, E.E. (Eric), Schlessinger, D. (David), Steinthorsdottir, V. (Valgerdur), Strachan, D.P. (David), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Di Blasio, A.M. (Anna Maria), Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia), Meyre, D. (David), Scherag, A. (Andre), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Loos, R.J.F. (Ruth), and Ingelsson, E. (Erik)
Abstract: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
Published: 2013
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15. Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropomet

Author: Randall, J.C. (Joshua), Winkler, T.W. (Thomas), Kutalik, Z. (Zoltán), Berndt, S.I. (Sonja), Jackson, A.U. (Anne), Monda, K.L. (Keri), Kilpeläinen, T.O. (Tuomas), Esko, T. (Tõnu), Mägi, R. (Reedik), Li, S. (Shengxu), Workalemahu, T. (Tsegaselassie), Feitosa, M.F. (Mary Furlan), Croteau-Chonka, D.C. (Damien), Day, F.R. (Felix), Fall, M. (Magnus), Ferreira, T. (Teresa), Gustafsson, S. (Stefan), Locke, A.E. (Adam), Mathieson, I. (Iain), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Liang, L. (Liming), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Dermitzakis, E.T. (Emmanouil), Dimas, A.S. (Antigone), Karpe, F. (Fredrik), Min, J. (Josine), Nicholson, G. (Ggeorge), Clegg, D.J. (Deborah), Person, A.D. (Anthony), Krohn, J.P. (Jon), Bauer, S. (Stephanie), Buechler, C. (Christa), Eisinger, F. (François), Bonnefond, A. (Amélie), Froguel, P. (Philippe), Hottenga, J.J. (Jouke Jan), Prokopenko, I. (Inga), Waite, L. (Lindsay), Harris, T.B. (Tamara), Smith, A.V. (Davey), Shuldiner, A.R. (Alan), McArdle, W.L. (Wendy), Caulfield, M. (Mark), Munroe, P. (Patricia), Grönberg, H. (Henrik), Chen, Y.D.I. (Yii-Der Ida), Li, G. (Guo), Beckmann, J.S. (Jacques), Johnson, T. (Toby), Thorsteinsdottir, U. (Unnur), Teder-Laving, M. (Maris), Khaw, K-T. (Kay-Tee), Wareham, N.J. (Nick), Zhao, J.H. (Jing Hua), Amin, N. (Najaf), Oostra, B.A. (Ben), Kraja, A. (Aldi), Province, M.A. (Mike), Cupples, L.A. (Adrienne), Heard-Costa, N.L. (Nancy), Kaprio, J. (Jaakko), Ripatti, S. (Samuli), Surakka, I. (Ida), Collins, F.S. (Francis), Saramies, J. (Jouko), Tuomilehto, J. (Jaakko), Jula, A. (Antti), Salomaa, V. (Veikko), Erdmann, J. (Jeanette), Hengstenberg, C. (Christian), Loley, C. (Christina), Schunkert, H. (Heribert), Lamina, C. (Claudia), Wichmann, H.E. (Heinz Erich), Albrecht, E. (Eva), Gieger, C. (Christian), Hicks, A.A. (Andrew), Johansson, A. (Åsa), Pramstaller, P.P. (Peter Paul), Kathiresan, S. (Sekar), Speliotes, E.K. (Elizabeth), Penninx, B.W.J.H. (Brenda), Hartikainen, A.L., Jarvelin, M.-R. (Marjo-Riitta), Gyllensten, U. (Ulf), Boomsma, D.I. (Dorret), Campbell, H. (Harry), Wilson, J.F. (James), Chanock, S.J. (Stephen), Farrall, M. (Martin), Goel, A. (Anuj), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Estrada Gil, K. (Karol), Uitterlinden, A.G. (André), Hofman, A. (Albert), Zillikens, M.C. (Carola), Heijer, M. (Martin) den, Kiemeney, L.A.L.M. (Bart), Maschio, A., Hall, A.S. (Alistair), Tyrer, J.P. (Jonathan), Teumer, A. (Alexander), Völzke, H. (Henry), Kovacs, P. (Peter), Tönjes, A. (Anke), Mangino, M. (Massimo), Spector, T.D. (Timothy), Hayward, C. (Caroline), Rudan, I. (Igor), Hall, A. (Anne), Samani, N.J. (Nilesh), Attwood, A.P. (Antony), Sambrook, J.G. (Jennifer), Hung, J. (Judy), Palmer, C. (Cameron), Lokki, M.L., Sinisalo, J. (Juha), Boucher, G. (Gabrielle), Huikuri, H.V. (Heikki), Lorentzon, M. (Mattias), Ohlsson, C. (Claes), Eklund, N. (Niina), Hagen, K. (Knut), Barlassina, C. (Christina), Rivolta, C. (Carlo), Nolte, I.M. (Ilja), Snieder, H. (Harold), Klauw, M.M. (Melanie) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Gejman, P.V. (Pablo), Shi, J. (Jianxin), Jacobs, K.B. (Kevin), Wang, Z. (Zhaoming), Bakker, S.J.L. (Stephan), Leach, I.M. (Irene Mateo), Navis, G. (Gerjan), Harst, P. (Pim) van der, Martin, N.G. (Nicholas), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Yang, J. (Joanna), Chasman, D.I. (Daniel), Ridker, P.M. (Paul), Rose, L.M. (Lynda), Lehtimäki, T. (Terho), Raitakari, O. (Olli), Absher, D. (Devin), Iribarren, C. (Carlos), Basart, D.C.G. (Dick), Hovingh, G.K. (Kees), Hyppönen, E. (Elina), Power, C. (Christopher), Beilby, J.P. (John), Hui, J. (Jennie), Jolley, G.J. (Jason), Sager, H. (Hendrik), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Kristiansson, K. (Kati), Perola, M. (Markus), Lindström, J. (Jaana), Swift, A.J. (Amy), Uusitupa, M. (Matti), Atalay, M. (Mustafa), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Bolton, J.L. (Jennifer), Fowkes, G. (Gerry), Fraser, R.M. (Ross), Price, J.F. (Jackie F.), Fischer, K. (Krista), KrjutÅkov, K. (Kaarel), Metspalu, A. (Andres), Mihailov, E. (Evelin), Langenberg, C. (Claudia), Luan, J., Ong, K.K. (Ken), Chines, P.S. (Peter), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Edkins, T. (Ted), Franks, P.W. (Paul), Hallmans, G. (Göran), Shungin, D. (Dmitry), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Erbel, R. (Raimund), Moebus, S. (Susanne), Nöthen, M.M. (Markus), Pechlivanis, S. (Sonali), Hveem, K. (Kristian), Narisu, N. (Narisu), Hamsten, A. (Anders), Humphries, S.E. (Steve), Strawbridge, R.J. (Rona), Tremoli, E. (Elena), Grallert, H. (Harald), Thorand, B. (Barbara), Illig, T. (Thomas), Koenig, W. (Wolfgang), Müller-Nurasyid, M. (Martina), Peters, A. (Annette), Boehm, B.O. (Bernhard), Kleber, M.E. (Marcus), März, W. (Winfried), Winkelmann, B., Kuusisto, J. (Johanna), Laakso, M. (Markku), Arveiler, D. (Dominique), Cesana, G. (Giancarlo), Kuulasmaa, K. (Kari), Virtamo, J. (Jarmo), Yarnell, J.W.G. (John W.), Kuh, D. (Diana), Wong, A. (Andrew), Lind, L. (Lars), Faire, U. (Ulf) de, Gigante, B. (Bruna), Magnusson, P.K. (Patrik), Pedersen, N.L. (Nancy), Dedoussis, G.V. (George), Dimitriou, M. (Maria), Kolovou, G. (Genovefa), Kanoni, S. (Stavroula), Stirrups, K. (Kathy), Bonnycastle, L.L. (Lori), Njølstad, I. (Inger), Wilsgaard, T. (Tom), Ganna, A. (Andrea), Rehnberg, E. (Emil), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C. (Craig), Frayling, T.M. (Timothy), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D. (David), Ingelsson, E. (Erik), Kaplan, R.C. (Robert), Mohlke, K.L. (Karen), O´Connell, J.R., Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Abecasis, G.R. (Gonçalo), McCarthy, M.I. (Mark), Anderson, D. (Denise), Hirschhorn, J.N. (Joel), Qi, L. (Lu), Loos, R.J.F. (Ruth), Lindgren, C.M. (Cecilia), North, K.E. (Kari), Heid, I.M. (Iris), Randall, J.C. (Joshua), Winkler, T.W. (Thomas), Kutalik, Z. (Zoltán), Berndt, S.I. (Sonja), Jackson, A.U. (Anne), Monda, K.L. (Keri), Kilpeläinen, T.O. (Tuomas), Esko, T. (Tõnu), Mägi, R. (Reedik), Li, S. (Shengxu), Workalemahu, T. (Tsegaselassie), Feitosa, M.F. (Mary Furlan), Croteau-Chonka, D.C. (Damien), Day, F.R. (Felix), Fall, M. (Magnus), Ferreira, T. (Teresa), Gustafsson, S. (Stefan), Locke, A.E. (Adam), Mathieson, I. (Iain), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Liang, L. (Liming), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Dermitzakis, E.T. (Emmanouil), Dimas, A.S. (Antigone), Karpe, F. (Fredrik), Min, J. (Josine), Nicholson, G. (Ggeorge), Clegg, D.J. (Deborah), Person, A.D. (Anthony), Krohn, J.P. (Jon), Bauer, S. (Stephanie), Buechler, C. (Christa), Eisinger, F. (François), Bonnefond, A. (Amélie), Froguel, P. (Philippe), Hottenga, J.J. (Jouke Jan), Prokopenko, I. (Inga), Waite, L. (Lindsay), Harris, T.B. (Tamara), Smith, A.V. (Davey), Shuldiner, A.R. (Alan), McArdle, W.L. (Wendy), Caulfield, M. (Mark), Munroe, P. (Patricia), Grönberg, H. (Henrik), Chen, Y.D.I. (Yii-Der Ida), Li, G. (Guo), Beckmann, J.S. (Jacques), Johnson, T. (Toby), Thorsteinsdottir, U. (Unnur), Teder-Laving, M. (Maris), Khaw, K-T. (Kay-Tee), Wareham, N.J. (Nick), Zhao, J.H. (Jing Hua), Amin, N. (Najaf), Oostra, B.A. (Ben), Kraja, A. (Aldi), Province, M.A. (Mike), Cupples, L.A. (Adrienne), Heard-Costa, N.L. (Nancy), Kaprio, J. (Jaakko), Ripatti, S. (Samuli), Surakka, I. (Ida), Collins, F.S. (Francis), Saramies, J. (Jouko), Tuomilehto, J. (Jaakko), Jula, A. (Antti), Salomaa, V. (Veikko), Erdmann, J. (Jeanette), Hengstenberg, C. (Christian), Loley, C. (Christina), Schunkert, H. (Heribert), Lamina, C. (Claudia), Wichmann, H.E. (Heinz Erich), Albrecht, E. (Eva), Gieger, C. (Christian), Hicks, A.A. (Andrew), Johansson, A. (Åsa), Pramstaller, P.P. (Peter Paul), Kathiresan, S. (Sekar), Speliotes, E.K. (Elizabeth), Penninx, B.W.J.H. (Brenda), Hartikainen, A.L., Jarvelin, M.-R. (Marjo-Riitta), Gyllensten, U. (Ulf), Boomsma, D.I. (Dorret), Campbell, H. (Harry), Wilson, J.F. (James), Chanock, S.J. (Stephen), Farrall, M. (Martin), Goel, A. (Anuj), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Estrada Gil, K. (Karol), Uitterlinden, A.G. (André), Hofman, A. (Albert), Zillikens, M.C. (Carola), Heijer, M. (Martin) den, Kiemeney, L.A.L.M. (Bart), Maschio, A., Hall, A.S. (Alistair), Tyrer, J.P. (Jonathan), Teumer, A. (Alexander), Völzke, H. (Henry), Kovacs, P. (Peter), Tönjes, A. (Anke), Mangino, M. (Massimo), Spector, T.D. (Timothy), Hayward, C. (Caroline), Rudan, I. (Igor), Hall, A. (Anne), Samani, N.J. (Nilesh), Attwood, A.P. (Antony), Sambrook, J.G. (Jennifer), Hung, J. (Judy), Palmer, C. (Cameron), Lokki, M.L., Sinisalo, J. (Juha), Boucher, G. (Gabrielle), Huikuri, H.V. (Heikki), Lorentzon, M. (Mattias), Ohlsson, C. (Claes), Eklund, N. (Niina), Hagen, K. (Knut), Barlassina, C. (Christina), Rivolta, C. (Carlo), Nolte, I.M. (Ilja), Snieder, H. (Harold), Klauw, M.M. (Melanie) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Gejman, P.V. (Pablo), Shi, J. (Jianxin), Jacobs, K.B. (Kevin), Wang, Z. (Zhaoming), Bakker, S.J.L. (Stephan), Leach, I.M. (Irene Mateo), Navis, G. (Gerjan), Harst, P. (Pim) van der, Martin, N.G. (Nicholas), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Yang, J. (Joanna), Chasman, D.I. (Daniel), Ridker, P.M. (Paul), Rose, L.M. (Lynda), Lehtimäki, T. (Terho), Raitakari, O. (Olli), Absher, D. (Devin), Iribarren, C. (Carlos), Basart, D.C.G. (Dick), Hovingh, G.K. (Kees), Hyppönen, E. (Elina), Power, C. (Christopher), Beilby, J.P. (John), Hui, J. (Jennie), Jolley, G.J. (Jason), Sager, H. (Hendrik), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Kristiansson, K. (Kati), Perola, M. (Markus), Lindström, J. (Jaana), Swift, A.J. (Amy), Uusitupa, M. (Matti), Atalay, M. (Mustafa), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Bolton, J.L. (Jennifer), Fowkes, G. (Gerry), Fraser, R.M. (Ross), Price, J.F. (Jackie F.), Fischer, K. (Krista), KrjutÅkov, K. (Kaarel), Metspalu, A. (Andres), Mihailov, E. (Evelin), Langenberg, C. (Claudia), Luan, J., Ong, K.K. (Ken), Chines, P.S. (Peter), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Edkins, T. (Ted), Franks, P.W. (Paul), Hallmans, G. (Göran), Shungin, D. (Dmitry), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Erbel, R. (Raimund), Moebus, S. (Susanne), Nöthen, M.M. (Markus), Pechlivanis, S. (Sonali), Hveem, K. (Kristian), Narisu, N. (Narisu), Hamsten, A. (Anders), Humphries, S.E. (Steve), Strawbridge, R.J. (Rona), Tremoli, E. (Elena), Grallert, H. (Harald), Thorand, B. (Barbara), Illig, T. (Thomas), Koenig, W. (Wolfgang), Müller-Nurasyid, M. (Martina), Peters, A. (Annette), Boehm, B.O. (Bernhard), Kleber, M.E. (Marcus), März, W. (Winfried), Winkelmann, B., Kuusisto, J. (Johanna), Laakso, M. (Markku), Arveiler, D. (Dominique), Cesana, G. (Giancarlo), Kuulasmaa, K. (Kari), Virtamo, J. (Jarmo), Yarnell, J.W.G. (John W.), Kuh, D. (Diana), Wong, A. (Andrew), Lind, L. (Lars), Faire, U. (Ulf) de, Gigante, B. (Bruna), Magnusson, P.K. (Patrik), Pedersen, N.L. (Nancy), Dedoussis, G.V. (George), Dimitriou, M. (Maria), Kolovou, G. (Genovefa), Kanoni, S. (Stavroula), Stirrups, K. (Kathy), Bonnycastle, L.L. (Lori), Njølstad, I. (Inger), Wilsgaard, T. (Tom), Ganna, A. (Andrea), Rehnberg, E. (Emil), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C. (Craig), Frayling, T.M. (Timothy), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D. (David), Ingelsson, E. (Erik), Kaplan, R.C. (Robert), Mohlke, K.L. (Karen), O´Connell, J.R., Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Abecasis, G.R. (Gonçalo), McCarthy, M.I. (Mark), Anderson, D. (Denise), Hirschhorn, J.N. (Joel), Qi, L. (Lu), Loos, R.J.F. (Ruth), Lindgren, C.M. (Cecilia), North, K.E. (Kari), and Heid, I.M. (Iris)
Published: 2013
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16. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author: Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. (Yvonne) van der, Casas, J.P. (Juan), Mohlke, K.L. (Karen), Vineis, P. (Paolo), Raitakari, O. (Olli), Ganesh, S.K. (Santhi), Shyong Tai, E., Laakso, M. (Markku), Rao, D.C. (Dabeeru C.), Harris, T.B. (Tamara), Morris, R.W. (Richard), Dominiczak, A. (Anna), Kivimaki, M. (Mika), Marmot, M. (Michael), Miki, T. (Tetsuro), Saleheen, D., Chandak, G.R. (Giriraj), Coresh, J. (Josef), Navis, G. (Gerjan), Salomaa, V. (Veikko), Han, B.-G., Kooner, J.S. (Jaspal), Melander, O. (Olle), Ridker, P.M. (Paul), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Tuomilehto, J. (Jaakko), Pramstaller, P.P. (Peter Paul), Elosua, R. (Roberto), Soranzo, N. (Nicole), Sijbrands, E.J.G. (Eric), Altshuler, D. (David), Loos, R.J.F. (Ruth), Shuldiner, A.R. (Alan), Gieger, C. (Christian), Meneton, P. (Pierre), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Gudnason, V. (Vilmundur), Rotter, J.I. (Jerome), Rettig, R. (Rainer), Uda, M. (Manuela), Strachan, D.P. (David), Witteman, J.C.M. (Jacqueline), Hartikainen, A.L., Beckmann, J.S. (Jacques), Boerwinkle, E.A. (Eric), Erdmann, J. (Jeanette), Vasan, R.S. (Ramachandran Srini), Boehnke, M. (Michael), Larson, M.G. (Martin), Järvelin, M.R., Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Newton-Cheh, C. (Christopher), Elliott, P. (Paul), Levy, D. (Daniel), Caulfield, M. (Mark), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda), Bakker, S.J.L. (Stephan), Barroso, I.E. (Inês), Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. (Yvonne) van der, Casas, J.P. (Juan), Mohlke, K.L. (Karen), Vineis, P. (Paolo), Raitakari, O. (Olli), Ganesh, S.K. (Santhi), Shyong Tai, E., Laakso, M. (Markku), Rao, D.C. (Dabeeru C.), Harris, T.B. (Tamara), Morris, R.W. (Richard), Dominiczak, A. (Anna), Kivimaki, M. (Mika), Marmot, M. (Michael), Miki, T. (Tetsuro), Saleheen, D., Chandak, G.R. (Giriraj), Coresh, J. (Josef), Navis, G. (Gerjan), Salomaa, V. (Veikko), Han, B.-G., Kooner, J.S. (Jaspal), Melander, O. (Olle), Ridker, P.M. (Paul), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Tuomilehto, J. (Jaakko), Pramstaller, P.P. (Peter Paul), Elosua, R. (Roberto), Soranzo, N. (Nicole), Sijbrands, E.J.G. (Eric), Altshuler, D. (David), Loos, R.J.F. (Ruth), Shuldiner, A.R. (Alan), Gieger, C. (Christian), Meneton, P. (Pierre), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Gudnason, V. (Vilmundur), Rotter, J.I. (Jerome), Rettig, R. (Rainer), Uda, M. (Manuela), Strachan, D.P. (David), Witteman, J.C.M. (Jacqueline), Hartikainen, A.L., Beckmann, J.S. (Jacques), Boerwinkle, E.A. (Eric), Erdmann, J. (Jeanette), Vasan, R.S. (Ramachandran Srini), Boehnke, M. (Michael), Larson, M.G. (Martin), Järvelin, M.R., Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Newton-Cheh, C. (Christopher), Elliott, P. (Paul), Levy, D. (Daniel), Caulfield, M. (Mark), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda), Bakker, S.J.L. (Stephan), and Barroso, I.E. (Inês)
Abstract: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 geno
Published: 2011
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17. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Author: Dupuis, J. (Josée), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Soranzo, N. (Nicole), Jackson, A.U. (Anne), Wheeler, E. (Eleanor), Glazer, N.L. (Nicole), Bouatia-Naji, N. (Nabila), Gloyn, A.L. (Anna), Lindgren, C.M. (Cecilia), Mägi, R. (Reedik), Morris, A.P. (Andrew), Randall, J.C. (Joshua), Johnson, T. (Toby), Elliott, P. (Paul), Rybin, D. (Denis), Thorleifsson, G. (Gudmar), Steinthorsdottir, V. (Valgerdur), Henneman, P. (Peter), Grallert, H. (Harald), Dehghan, A. (Abbas), JanHottenga, J. (Jouke), Franklin, C.S. (Christopher), Navarro, P. (Pau), Song, K. (Kijoung), Goel, A. (Anuj), Perry, J.R.B. (John), Egan, J.M. (Josephine), Lajunen, T. (Taina), Grarup, N. (Niels), Sparsø, T. (Thomas), Doney, A.S.F. (Alex), Voight, B.F. (Benjamin), Stringham, H.M. (Heather), Li, M. (Man), Kanoni, S. (Stavroula), Shrader, P. (Peter), Cavalcanti-Proença, C. (Christine), Kumari, M. (Meena), Qi, L. (Lu), Timpson, N.J. (Nicholas), Gieger, C. (Christian), Zabena, C. (Carina), Rocheleau, G. (Ghislain), Ingelsson, E. (Erik), An, P. (Ping), O´Connell, J.R., Luan, J., McCarroll, S.A. (Steven), Payne, F. (Felicity), Roccasecca, R.M., Pattou, F. (François), Sethupathy, P. (Praveen), Ardlie, K.G. (Kristin), Ariyurek, Y. (Yavuz), Balkau, B. (Beverley), Barter, P. (Phil), Beilby, J.P. (John), Ben-Shlomo, Y., Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Bergmann, S.M. (Sven), Bochud, M. (Murielle), Boerwinkle, E.A. (Eric), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borch-Johnsen, K., Böttcher, Y. (Yvonne), Brunner, E. (Eric), Bumpstead, S. (Suzannah), Charpentier, G. (Guillaume), IdaChen, Y. (Yii) der, Chines, P.S. (Peter), Clarke, R., McOin, L.J. (Lachlan), Cooper, M.N. (Matthew), Cornelis, M. (Marilyn), Crawford, G. (Gabe), Crisponi, L. (Laura), Day, I.N.M. (Ian), Geus, E.J.C. (Eco) de, Delplanque, J. (Jerome), Dina, C. (Christian), Erdos, M.R. (Michael), Fedson, A.C. (Annette), Fischer-Rosinsky, A. (Antje), Forouhi, N.G. (Nita), Fox, C.S. (Caroline), Frants, R.R. (Rune), GraziaFranzosi, M. (Maria), Galan, P. (Pilar), Goodarzi, M. (Mark), Graessler, J. (Jürgen), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Gwilliam, R. (Rhian), Gyllensten, U. (Ulf), Hadjadj, S. (Samy), Hallmans, G. (Göran), Hammond, N. (Naomi), Han, X. (Xijing), Hartikainen, A.-L. (Anna-Liisa), Hassanali, N. (Neelam), Hayward, C. (Caroline), Heath, S.C. (Simon), Hercberg, S. (Serge), Herder, C. (Christian), Hicks, A.A. (Andrew), Hillman, D.R. (David), Hingorani, A. (Aroon), Hofman, A. (Albert), Hui, J. (Jennie), Hung, J. (Judy), Isomaa, B. (Bo), Jørgensen, T. (Torben), Jula, A. (Antti), Kaakinen, M. (Marika), Kaprio, J. (Jaakko), AnteroKesaniemi, Y., Kivimaki, M. (Mika), Knight, B. (Beatrice), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyvik, K.O. (Kirsten Ohm), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Bacquer, O.L. (Olivier), Lecoeur, C. (Cécile), Lyssenko, V. (Valeriya), Mahley, R. (Robert), Mangino, M. (Massimo), Manning, A.K. (Alisa), TeresaMartínez-Larrad, M. (María), McAteer, J.B. (Jarred), McCulloch, L.J. (Laura), McPherson, R. (Ruth), Meisinger, C. (Christa), Melzer, D. (David), Meyre, D. (David), Mitchell, B.D. (Braxton), Morken, M.A. (Mario), Mukherjee, S. (Sutapa), Naitza, S. (Silvia), Narisu, N. (Narisu), Neville, M.J. (Matthew), Oostra, B.A. (Ben), Orrù, M. (Marco), Pakyz, R. (Ruth), Palmer, C.N.A. (Colin), Paolisso, G. (Giuseppe), Pattaro, C. (Cristian), Pearson, D. (Daniel), Peden, J. (John), Pedersen, N.L. (Nancy), Perola, M. (Markus), Pfeiffer, A.F.H. (Andreas), Pichler, I. (Irene), Polasek, O. (Ozren), Posthuma, D. (Danielle), Potter, S.C. (Simon), Pouta, A. (Anneli), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Rice, K. (Kenneth), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Roden, M. (Michael), Rolandsson, O. (Olov), Sandbaek, A. (Annelli), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Sayer, A.A., Scheet, P. (Paul), Scott, L.J. (Laura), Seedorf, U. (Udo), Sharp, S.J. (Stephen), Shields, B.M. (Beverley), Sigursson, G. (Gunnar), Sijbrands, E.J.G. (Eric), Silveira, A. (Angela), Simpson, L. (Laila), Singleton, A. (Andrew), Smith, N.L. (Nicholas), Sovio, U. (Ulla), Swift, A.J. (Amy), Syddall, H. (Holly), Syvänen, A.-C. (Ann-Christine), Tanaka, T. (Toshiko), Thorand, B. (Barbara), Tichet, J. (Jean), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Uitterlinden, A.G. (André), Willems van Dijk, J.A.P. (Ko), Hoek, M. (Mandy) van, Varma, D. (Dhiraj), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogelzangs, N. (Nicole), Waeber, G. (Gérard), Wagner, P.J. (Peter), Walley, A. (Andrew), BragiWalters, G., Ward, K.L. (Kim), Watkins, H. (Hugh), Weedon, M.N. (Michael), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), GYarnell, J.W. (John), Zeggini, E. (Eleftheria), Zelenika, D. (Diana), Zethelius, B. (Björn), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Meneton, P. (Pierre), Magnusson, P.K. (Patrik), Nathan, D.M. (David), Williams, G.H. (Gordon), Hattersley, A.T. (Andrew), Silander, K. (Kaisa), Salomaa, V. (Veikko), Bornstein, S.R. (Stefan), Schwarz, P. (Peter), Spranger, J. (Jürgen), Karpe, F. (Fredrik), Shuldiner, A.R. (Alan), Dedoussis, G.V. (George), Serrano-Ríos, M. (Manuel), Lind, L. (Lars), Palmer, C. (Cameron), Hu, F.B. (Frank), Franks, P.W. (Paul), Ebrahim, S. (Shanil), Marmot, M. (Michael), Kao, W.-H.L. (Linda), Pankow, J.S. (James), Sampson, M.J. (Michael), Kuusisto, J. (Johanna), Laakso, M. (Markku), Hansen, T. (Torben), Pramstaller, P.P. (Peter Paul), Wichmann, H.E. (Erich), Illig, T. (Thomas), Rudan, I. (Igor), Wright, A.F. (Alan), Stumvoll, M. (Michael), Campbell, H. (Harry), Wilson, J.F. (James), Bergman, R.N. (Richard), Buchanan, T.A. (Thomas), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Altshuler, D. (David), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Deloukas, P. (Panagiotis), Spector, T.D. (Timothy), Frayling, T.M. (Timothy), Ferrucci, L. (Luigi), Kong, A. (Augustine), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Cao, A. (Antonio), Scuteri, A. (Angelo), Schlessinger, D. (David), Uda, M. (Manuela), Ruokonen, A. (Aimo), Jarvelin, M.-R. (Marjo-Riitta), Waterworth, D. (Dawn), Vollenweider, P. (Peter), Peltonen, L. (Leena Johanna), Mooser, V. (Vincent), Abecasis, G.R. (Gonçalo), Wareham, N.J. (Nick), Sladek, R. (Rob), Froguel, P. (Philippe), Meigs, J.B. (James), Groop, L. (Leif), Watanabe, R.M. (Richard), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Florez, J.C. (Jose), Barroso, I.E. (Inês), Dupuis, J. (Josée), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Soranzo, N. (Nicole), Jackson, A.U. (Anne), Wheeler, E. (Eleanor), Glazer, N.L. (Nicole), Bouatia-Naji, N. (Nabila), Gloyn, A.L. (Anna), Lindgren, C.M. (Cecilia), Mägi, R. (Reedik), Morris, A.P. (Andrew), Randall, J.C. (Joshua), Johnson, T. (Toby), Elliott, P. (Paul), Rybin, D. (Denis), Thorleifsson, G. (Gudmar), Steinthorsdottir, V. (Valgerdur), Henneman, P. (Peter), Grallert, H. (Harald), Dehghan, A. (Abbas), JanHottenga, J. (Jouke), Franklin, C.S. (Christopher), Navarro, P. (Pau), Song, K. (Kijoung), Goel, A. (Anuj), Perry, J.R.B. (John), Egan, J.M. (Josephine), Lajunen, T. (Taina), Grarup, N. (Niels), Sparsø, T. (Thomas), Doney, A.S.F. (Alex), Voight, B.F. (Benjamin), Stringham, H.M. (Heather), Li, M. (Man), Kanoni, S. (Stavroula), Shrader, P. (Peter), Cavalcanti-Proença, C. (Christine), Kumari, M. (Meena), Qi, L. (Lu), Timpson, N.J. (Nicholas), Gieger, C. (Christian), Zabena, C. (Carina), Rocheleau, G. (Ghislain), Ingelsson, E. (Erik), An, P. (Ping), O´Connell, J.R., Luan, J., McCarroll, S.A. (Steven), Payne, F. (Felicity), Roccasecca, R.M., Pattou, F. (François), Sethupathy, P. (Praveen), Ardlie, K.G. (Kristin), Ariyurek, Y. (Yavuz), Balkau, B. (Beverley), Barter, P. (Phil), Beilby, J.P. (John), Ben-Shlomo, Y., Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Bergmann, S.M. (Sven), Bochud, M. (Murielle), Boerwinkle, E.A. (Eric), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borch-Johnsen, K., Böttcher, Y. (Yvonne), Brunner, E. (Eric), Bumpstead, S. (Suzannah), Charpentier, G. (Guillaume), IdaChen, Y. (Yii) der, Chines, P.S. (Peter), Clarke, R., McOin, L.J. (Lachlan), Cooper, M.N. (Matthew), Cornelis, M. (Marilyn), Crawford, G. (Gabe), Crisponi, L. (Laura), Day, I.N.M. (Ian), Geus, E.J.C. (Eco) de, Delplanque, J. (Jerome), Dina, C. (Christian), Erdos, M.R. (Michael), Fedson, A.C. (Annette), Fischer-Rosinsky, A. (Antje), Forouhi, N.G. (Nita), Fox, C.S. (Caroline), Frants, R.R. (Rune), GraziaFranzosi, M. (Maria), Galan, P. (Pilar), Goodarzi, M. (Mark), Graessler, J. (Jürgen), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Gwilliam, R. (Rhian), Gyllensten, U. (Ulf), Hadjadj, S. (Samy), Hallmans, G. (Göran), Hammond, N. (Naomi), Han, X. (Xijing), Hartikainen, A.-L. (Anna-Liisa), Hassanali, N. (Neelam), Hayward, C. (Caroline), Heath, S.C. (Simon), Hercberg, S. (Serge), Herder, C. (Christian), Hicks, A.A. (Andrew), Hillman, D.R. (David), Hingorani, A. (Aroon), Hofman, A. (Albert), Hui, J. (Jennie), Hung, J. (Judy), Isomaa, B. (Bo), Jørgensen, T. (Torben), Jula, A. (Antti), Kaakinen, M. (Marika), Kaprio, J. (Jaakko), AnteroKesaniemi, Y., Kivimaki, M. (Mika), Knight, B. (Beatrice), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyvik, K.O. (Kirsten Ohm), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Bacquer, O.L. (Olivier), Lecoeur, C. (Cécile), Lyssenko, V. (Valeriya), Mahley, R. (Robert), Mangino, M. (Massimo), Manning, A.K. (Alisa), TeresaMartínez-Larrad, M. (María), McAteer, J.B. (Jarred), McCulloch, L.J. (Laura), McPherson, R. (Ruth), Meisinger, C. (Christa), Melzer, D. (David), Meyre, D. (David), Mitchell, B.D. (Braxton), Morken, M.A. (Mario), Mukherjee, S. (Sutapa), Naitza, S. (Silvia), Narisu, N. (Narisu), Neville, M.J. (Matthew), Oostra, B.A. (Ben), Orrù, M. (Marco), Pakyz, R. (Ruth), Palmer, C.N.A. (Colin), Paolisso, G. (Giuseppe), Pattaro, C. (Cristian), Pearson, D. (Daniel), Peden, J. (John), Pedersen, N.L. (Nancy), Perola, M. (Markus), Pfeiffer, A.F.H. (Andreas), Pichler, I. (Irene), Polasek, O. (Ozren), Posthuma, D. (Danielle), Potter, S.C. (Simon), Pouta, A. (Anneli), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Rice, K. (Kenneth), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Roden, M. (Michael), Rolandsson, O. (Olov), Sandbaek, A. (Annelli), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Sayer, A.A., Scheet, P. (Paul), Scott, L.J. (Laura), Seedorf, U. (Udo), Sharp, S.J. (Stephen), Shields, B.M. (Beverley), Sigursson, G. (Gunnar), Sijbrands, E.J.G. (Eric), Silveira, A. (Angela), Simpson, L. (Laila), Singleton, A. (Andrew), Smith, N.L. (Nicholas), Sovio, U. (Ulla), Swift, A.J. (Amy), Syddall, H. (Holly), Syvänen, A.-C. (Ann-Christine), Tanaka, T. (Toshiko), Thorand, B. (Barbara), Tichet, J. (Jean), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Uitterlinden, A.G. (André), Willems van Dijk, J.A.P. (Ko), Hoek, M. (Mandy) van, Varma, D. (Dhiraj), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogelzangs, N. (Nicole), Waeber, G. (Gérard), Wagner, P.J. (Peter), Walley, A. (Andrew), BragiWalters, G., Ward, K.L. (Kim), Watkins, H. (Hugh), Weedon, M.N. (Michael), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), GYarnell, J.W. (John), Zeggini, E. (Eleftheria), Zelenika, D. (Diana), Zethelius, B. (Björn), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Meneton, P. (Pierre), Magnusson, P.K. (Patrik), Nathan, D.M. (David), Williams, G.H. (Gordon), Hattersley, A.T. (Andrew), Silander, K. (Kaisa), Salomaa, V. (Veikko), Bornstein, S.R. (Stefan), Schwarz, P. (Peter), Spranger, J. (Jürgen), Karpe, F. (Fredrik), Shuldiner, A.R. (Alan), Dedoussis, G.V. (George), Serrano-Ríos, M. (Manuel), Lind, L. (Lars), Palmer, C. (Cameron), Hu, F.B. (Frank), Franks, P.W. (Paul), Ebrahim, S. (Shanil), Marmot, M. (Michael), Kao, W.-H.L. (Linda), Pankow, J.S. (James), Sampson, M.J. (Michael), Kuusisto, J. (Johanna), Laakso, M. (Markku), Hansen, T. (Torben), Pramstaller, P.P. (Peter Paul), Wichmann, H.E. (Erich), Illig, T. (Thomas), Rudan, I. (Igor), Wright, A.F. (Alan), Stumvoll, M. (Michael), Campbell, H. (Harry), Wilson, J.F. (James), Bergman, R.N. (Richard), Buchanan, T.A. (Thomas), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Altshuler, D. (David), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Deloukas, P. (Panagiotis), Spector, T.D. (Timothy), Frayling, T.M. (Timothy), Ferrucci, L. (Luigi), Kong, A. (Augustine), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Cao, A. (Antonio), Scuteri, A. (Angelo), Schlessinger, D. (David), Uda, M. (Manuela), Ruokonen, A. (Aimo), Jarvelin, M.-R. (Marjo-Riitta), Waterworth, D. (Dawn), Vollenweider, P. (Peter), Peltonen, L. (Leena Johanna), Mooser, V. (Vincent), Abecasis, G.R. (Gonçalo), Wareham, N.J. (Nick), Sladek, R. (Rob), Froguel, P. (Philippe), Meigs, J.B. (James), Groop, L. (Leif), Watanabe, R.M. (Richard), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Florez, J.C. (Jose), and Barroso, I.E. (Inês)
Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Published: 2010
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18. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Author: Voight, B.F. (Benjamin), Scott, L.J. (Laura), Steinthorsdottir, V. (Valgerdur), Morris, A.D. (Andrew), Dina, C. (Christian), Welch, R.P. (Ryan), Zeggini, E. (Eleftheria), Huth, C. (Cornelia), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), McCulloch, L.J. (Laura), Ferreira, T. (Teresa), Grallert, H. (Harald), Amin, N. (Najaf), Wu, G. (Guanming), Willer, C.J. (Cristen), Raychaudhuri, S. (Soumya), McCarroll, S.A. (Steven), Langenberg, C. (Claudia), Hofmann, O.M. (Oliver), Dupuis, J. (Josée), Qi, L. (Lu), Segrè, A.V. (Ayellet), Hoek, M. (Mandy) van, Navarro, P. (Pau), Ardlie, K.G. (Kristin), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Blagieva, R. (Roza), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boström, K.B. (Kristina Bengtsson), Bravenboer, B. (Bert), Bumpstead, S. (Suzannah), Burtt, N.P. (Noël), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David), Crawford, G. (Gabe), Doney, A.S.F. (Alex), Elliott, K.S. (Katherine), Erdos, M.R. (Michael), Fox, C.S. (Caroline), Franklin, C.S. (Christopher), Ganser, M. (Martha), Gieger, C. (Christian), Grarup, N. (Niels), Green, T. (Todd), Griffin, S. (Simon), Groves, C.J. (Christopher), Guiducci, C. (Candace), Hadjadj, S. (Samy), Hassanali, N. (Neelam), Herder, C. (Christian), Isomaa, B. (Bo), Jackson, A.U. (Anne), Johnson, P.R.V. (Paul), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Klopp, N. (Norman), Kong, A. (Augustine), Kraft, P. (Peter), Kuusisto, J. (Johanna), Lauritzen, T. (Torsten), Li, M. (Man), Lieverse, A.G. (Aloysius), Lindgren, C.M. (Cecilia), Lyssenko, V. (Valeriya), Marre, M. (Michel), Meitinger, T. (Thomas), Midthjell, K. (Kristian), Morken, M.A. (Mario), Narisu, N. (Narisu), Nilsson, P. (Peter), Owen, K.R. (Katharine), Payne, F. (Felicity), Perry, J.R.B. (John), Petersen, A.K., Platou, C. (Carl), Proença, C. (Christine), Prokopenko, I. (Inga), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Rocheleau, G. (Ghislain), Roden, M. (Michael), Sampson, M.J. (Michael), Saxena, R. (Richa), Shields, B.M. (Beverley), Shrader, P. (Peter), Sigurdsson, G. (Gunnar), Sparsø, T. (Thomas), Strassburger, K. (Klaus), Stringham, H.M. (Heather), Sun, Q. (Qi), Swift, A.J. (Amy), Thorand, B. (Barbara), Tichet, J. (Jean), Tuomi, T. (Tiinamaija), Dam, R.M. (Rob) van, Haeften, T.W. (Timon) van, Herpt, T.W. (Thijs) van, Vliet-Ostaptchouk, J.V. (Jana) van, Walters, G.B. (Bragi), Weedon, M.N. (Michael), Wijmenga, C. (Cisca), Witteman, J.C.M. (Jacqueline), Bergman, R.N. (Richard), Cauchi, S. (Stephane), Collins, F.S. (Francis), Gloyn, A.L. (Anna), Gyllensten, U. (Ulf), Hansen, T. (Torben), Hide, W.A. (Winston), Hitman, G.A. (Graham), Hofman, A. (Albert), Hunter, D. (David), Hveem, K. (Kristian), Laakso, M. (Markku), Mohlke, K.L. (Karen), Palmer, C.N.A. (Colin), Pramstaller, P.P. (Peter Paul), Rudan, I. (Igor), Sijbrands, E.J.G. (Eric), Stein, L.D. (Lincoln), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Walker, M. (Mark), Wareham, N.J. (Nick), Abecasis, G.R. (Gonçalo), Boehm, B.O. (Bernhard), Campbell, H. (Harry), Daly, M.J. (Mark), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Meigs, J.B. (James), Pankow, J.S. (James), Pedersen, O. (Oluf), Wichmann, H.E. (Erich), Barroso, I.E. (Inês), Florez, J.C. (Jose), Frayling, T.M. (Timothy), Groop, L. (Leif), Sladek, R. (Rob), Thorsteinsdottir, U. (Unnur), Wilson, J.F. (James), Illig, T. (Thomas), Froguel, P. (Philippe), Tikka-Kleemola, P. (Päivi), Zwart, J-A. (John-Anker), Altshuler, D. (David), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Watanabe, R.M. (Richard), Voight, B.F. (Benjamin), Scott, L.J. (Laura), Steinthorsdottir, V. (Valgerdur), Morris, A.D. (Andrew), Dina, C. (Christian), Welch, R.P. (Ryan), Zeggini, E. (Eleftheria), Huth, C. (Cornelia), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), McCulloch, L.J. (Laura), Ferreira, T. (Teresa), Grallert, H. (Harald), Amin, N. (Najaf), Wu, G. (Guanming), Willer, C.J. (Cristen), Raychaudhuri, S. (Soumya), McCarroll, S.A. (Steven), Langenberg, C. (Claudia), Hofmann, O.M. (Oliver), Dupuis, J. (Josée), Qi, L. (Lu), Segrè, A.V. (Ayellet), Hoek, M. (Mandy) van, Navarro, P. (Pau), Ardlie, K.G. (Kristin), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Blagieva, R. (Roza), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boström, K.B. (Kristina Bengtsson), Bravenboer, B. (Bert), Bumpstead, S. (Suzannah), Burtt, N.P. (Noël), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David), Crawford, G. (Gabe), Doney, A.S.F. (Alex), Elliott, K.S. (Katherine), Erdos, M.R. (Michael), Fox, C.S. (Caroline), Franklin, C.S. (Christopher), Ganser, M. (Martha), Gieger, C. (Christian), Grarup, N. (Niels), Green, T. (Todd), Griffin, S. (Simon), Groves, C.J. (Christopher), Guiducci, C. (Candace), Hadjadj, S. (Samy), Hassanali, N. (Neelam), Herder, C. (Christian), Isomaa, B. (Bo), Jackson, A.U. (Anne), Johnson, P.R.V. (Paul), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Klopp, N. (Norman), Kong, A. (Augustine), Kraft, P. (Peter), Kuusisto, J. (Johanna), Lauritzen, T. (Torsten), Li, M. (Man), Lieverse, A.G. (Aloysius), Lindgren, C.M. (Cecilia), Lyssenko, V. (Valeriya), Marre, M. (Michel), Meitinger, T. (Thomas), Midthjell, K. (Kristian), Morken, M.A. (Mario), Narisu, N. (Narisu), Nilsson, P. (Peter), Owen, K.R. (Katharine), Payne, F. (Felicity), Perry, J.R.B. (John), Petersen, A.K., Platou, C. (Carl), Proença, C. (Christine), Prokopenko, I. (Inga), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Rocheleau, G. (Ghislain), Roden, M. (Michael), Sampson, M.J. (Michael), Saxena, R. (Richa), Shields, B.M. (Beverley), Shrader, P. (Peter), Sigurdsson, G. (Gunnar), Sparsø, T. (Thomas), Strassburger, K. (Klaus), Stringham, H.M. (Heather), Sun, Q. (Qi), Swift, A.J. (Amy), Thorand, B. (Barbara), Tichet, J. (Jean), Tuomi, T. (Tiinamaija), Dam, R.M. (Rob) van, Haeften, T.W. (Timon) van, Herpt, T.W. (Thijs) van, Vliet-Ostaptchouk, J.V. (Jana) van, Walters, G.B. (Bragi), Weedon, M.N. (Michael), Wijmenga, C. (Cisca), Witteman, J.C.M. (Jacqueline), Bergman, R.N. (Richard), Cauchi, S. (Stephane), Collins, F.S. (Francis), Gloyn, A.L. (Anna), Gyllensten, U. (Ulf), Hansen, T. (Torben), Hide, W.A. (Winston), Hitman, G.A. (Graham), Hofman, A. (Albert), Hunter, D. (David), Hveem, K. (Kristian), Laakso, M. (Markku), Mohlke, K.L. (Karen), Palmer, C.N.A. (Colin), Pramstaller, P.P. (Peter Paul), Rudan, I. (Igor), Sijbrands, E.J.G. (Eric), Stein, L.D. (Lincoln), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Walker, M. (Mark), Wareham, N.J. (Nick), Abecasis, G.R. (Gonçalo), Boehm, B.O. (Bernhard), Campbell, H. (Harry), Daly, M.J. (Mark), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Meigs, J.B. (James), Pankow, J.S. (James), Pedersen, O. (Oluf), Wichmann, H.E. (Erich), Barroso, I.E. (Inês), Florez, J.C. (Jose), Frayling, T.M. (Timothy), Groop, L. (Leif), Sladek, R. (Rob), Thorsteinsdottir, U. (Unnur), Wilson, J.F. (James), Illig, T. (Thomas), Froguel, P. (Philippe), Tikka-Kleemola, P. (Päivi), Zwart, J-A. (John-Anker), Altshuler, D. (David), Boehnke, M. (Michael), McCarthy, M.I. (Mark), and Watanabe, R.M. (Richard)
Abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P 5 × 10 8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap
Published: 2010
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19. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author: Speliotes, E.K. (Elizabeth), Willer, C.J. (Cristen), Berndt, S.I. (Sonja), Monda, K.L. (Keri), Thorleifsson, G. (Gudmar), Jackson, A.U. (Anne), Allen, H.L., Lindgren, C.M. (Cecilia), Luan, J., Mägi, R. (Reedik), Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Winkler, T.W. (Thomas), Qi, L. (Lu), Workalemahu, T. (Tsegaselassie), Heid, I.M. (Iris), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Wheeler, E. (Eleanor), Wood, A.R. (Andrew), Ferreira, T. (Teresa), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Eestrada, K. (Karol), Liang, L. (Liming), Nemesh, J. (James), Park, J.H., Gustafsson, S. (Stefan), Kilpeläinen, T.O. (Tuomas), Yang, J. (Joanna), Bouatia-Naji, N. (Nabila), Eesko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Kutalik, Z. (Zoltán), Mangino, M. (Massimo), Raychaudhuri, S. (Soumya), Scherag, A. (Andre), Smith, A.V. (Albert Vernon), Welch, R.P. (Ryan), Zhao, J.H. (Jing Hua), Aben, K.K.H. (Katja), Absher, D. (Devin), Amin, N. (Najaf), Dixon, A.L. (Anna), Fisher, E. (Eeva), Glazer, N.L. (Nicole), Goddard, M.E. (Michael), Heard-Costa, N.L. (Nancy), Hoesel, V. (Volker), Hottenga, J.J. (Jouke Jan), Johansson, A. (Åsa), Johnson, T. (Toby), Ketkar, S. (Shamika), Lamina, C. (Claudia), Li, S. (Shengxu), Moffatt, M.F. (Miriam), Myers, R.H. (Richard), Narisu, N. (Narisu), Perry, J.R.B. (John), Peters, M.J. (Marjolein), Preuss, M. (Michael), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Sandholt, C. (Camilla), Scott, L.J. (Laura), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Wingerden, S. (Sophie) van, White, C.C. (Charles), Wiklund, F. (Fredrik), Barlassina, C. (Christina), Chasman, D.I. (Daniel), Cooper, M.N. (Matthew), Jansson, J.O., Lawrence, R.W. (Robert), Pellikka, N. (Niina), Prokopenko, I. (Inga), Shi, J. (Jianxin), Thiering, E. (Eelisabeth), Alavere, H. (Helene), Alibrandi, M.T.S. (Maria), Almgren, P. (Peter), Arnold, A.M. (Alice), Aspelund, T. (Thor), Atwood, L.D. (Larry), Balkau, B. (Beverley), Balmforth, A.J. (Anthony), Bennett, A.J. (Amanda), Ben-Shlomo, Y., Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Biebermann, H. (Heike), Blakemore, A.I.F. (Alexandra), Boes, T. (Tanja), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Buchanan, T.A. (Thomas), Busonero, F., Campbell, H. (Harry), Cappuccio, F.P. (Francesco), Cavalcanti-Proença, C. (Christine), Chen, Y.D.I. (Yii-Der Ida), Chen, C.-M. (Chih-Mei), Chines, P.S. (Peter), Clarke, R., Coin, L. (Lachlan), Connell, J. (John), Day, I.N.M. (Ian), Heijer, M. (Martin) den, Duan, J. (Jubao), Eebrahim, S. (Shah), Eelliott, P. (Paul), Eelosua, R. (Roberto), Eeiriksdottir, G. (Gudny), Eerdos, M.R. (Micheal), Eeriksson, J.G. (Johan), Facheris, M.F. (Maurizio), Felix, S.B. (Stephan), Fischer-Posovszky, P. (Pamela), Folsom, A.R. (Aaron), Friedrich, N. (Nele), Freimer, N.B. (Nelson), Fu, M. (Mao), Gaget, S. (Stefan), Gejman, P.V. (Pablo), Geus, E.J.C. (Eco) de, Gieger, C. (Christian), Gjesing, A.P. (Anette), Goel, A. (Anuj), Goyette, P. (Philippe), Grallert, H. (Harald), Gräßler, J. (Jürgen), Greenawalt, D. (Danielle), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Guiducci, C. (Candace), Hartikainen, A.L., Hassanali, N. (Neelam), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Heath, A.C. (Andrew), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hinney, A. (Anke), Hofman, A. (Albert), Homuth, G. (Georg), Hui, J. (Jennie), Igl, W. (Wilmar), Iribarren, C. (Carlos), Isomaa, B. (Bo), Jacobs, K.B. (Kevin), Jarick, I. (Ivonne), Jewell, E. (Eelizabeth), John, U. (Ulrich), Jørgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaakinen, M. (Marika), Kajantie, E. (Eero), Kaplan, R.C. (Robert), Kathiresan, S. (Sekar), Kettunen, J. (Johannes), Kinnunen, L. (Leena), Knowles, J.W. (Joshua), Kolcic, I. (Ivana), König, I.R. (Inke), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kusisto, J. (Johanna), Kraft, P. (Peter), Kvaløy, K. (Kirsti), Laitinen, J. (Jaana), Lantieri, O. (Olivier), Lanzani, C. (Chiara), Launer, L.J. (Lenore), Lecoeur, C. (Cécile), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Liu, J. (Jianjun), Lokki, M.L., Lorentzon, M. (Mattias), Luben, R.N. (Robert), Ludwig, B. (Barbara), Manunta, P. (Paolo), Marek, D. (Diana), Marre, M. (Michel), Martin, N.G. (Nicholas), McArdle, W.L. (Wendy), McCarthy, M.I. (Mark), McKnight, B. (Barbara), Meitinger, T. (Thomas), Melander, O. (Olle), Meyre, D. (David), Midthjell, K. (Kristian), Montgomery, G.W. (Grant), Morken, M.A. (Mario), Morris, A.D. (Andrew), Mulic, R. (Rosanda), Ngwa, J.S., Nelis, M. (Mari), Neville, M.J. (Matthew), Nyholt, D.R. (Dale), O'Ddonnell, C.J. (Christopher), O'Rahilly, S. (Stephen), Ong, K. (Ken), Oostra, B.A. (Ben), Paré, G. (Guillaume), Parker, A.N. (Alex), Perola, M. (Markus), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Platou, C.P. (Carl), Polasek, O. (Ozren), Pouta, A. (Anneli), Rafelt, S. (Suzanne), Raitakari, O. (Olli), Rayner, N.W. (Nigel William), Ridderstråle, M. (Martin), Rief, W. (Winfried), Ruokonen, A. (Aimo), Robertson, N.R. (Neil), Rzehak, P. (Peter), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Saramies, J. (Jouko), Savolainen, M.J. (Markku), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Silander, K. (Kaisa), Sinisalo, J. (Juha), Siscovick, D.S. (David), Smit, J.H. (Jan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Stephens, J. (Jonathan), Surakka, I. (Ida), Swift, A.J. (Amy), Tammesoo, M.L., Tardif, J.-C. (Jean-Claude), Teder-Laving, M. (Maris), Teslovich, T.M. (Tanya), Thompson, J.R. (John), Thomson, B. (Brian), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Meurs, J.B.J. (Joyce) van, OMen, G.J. van, Vatin, V. (Vincent), Viikari, J. (Jorma), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogel, C.I. (Carla), Voight, B.F. (Benjamin), Waite, L. (Lindsay), Wallaschofski, H. (Henri), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wiegand, S. (Susanna), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witte, D.R. (Deniel), Witteman, J.C.M. (Jacqueline), Xu, J. (Jianfeng), Zhang, Q. (Qunyuan), Zgaga, L. (Lina), Ziegler, A. (Andreas), Zitting, P. (Paavo), Beilby, J.P. (John), FarOqi, I.S. (Ssadaf), Hebebrand, J. (Johannes), Huikuri, H.V. (Heikki), James, A. (Alan), Kähönen, M. (Mika), Levinson, D.F. (Douglas), MacCiardi, F. (Fabio), Nieminen, M.S. (Markku), Ohlsson, C. (Claes), Palmer, C. (Cameron), Ridker, P.M. (Paul), Stumvoll, M. (Michael), Beckmann, J.S. (Jacques), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Collins, F.S. (Francis), Cupples, L.A. (Adrienne), Eerdmann, J. (Jeanette), Frogue, P. (Philippe), Grönberg, H. (Henrik), Gyllensten, U. (Ulf), Hansen, T. (Torben), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayes, R.B. (Richard), Heinrich, J. (Joachim), Hu, F.B. (Frank), Hveem, K. (Kristian), Illig, T. (Thomas), Järvelin, M.R., Kaprio, J. (Jaakko), Karpe, F. (Fredrik), Khaw, K-T. (Kay-Tee), Kiemeney, L.A.L.M. (Bart), Krude, H., Laakso, M. (Markku), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Reinehr, T. (Thomas), Rissanen, A. (Aila), Rudan, I. (Igor), Samani, N.J. (Nilesh), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Spector, T.D. (Timothy), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Valle, T.T. (Timo), Wabitsch, M. (Martin), Waeber, G. (Gérard), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Wright, A.F. (Alan), Zillikens, M.C. (Carola), ChatterjE, N. (Nilanjan), McCarroll, S.A. (Steve), Purcell, S. (Shaun), Schadt, E.E. (Eric), Visscher, P.M. (Peter), Assimes, T.L. (Themistocles), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D.J. (David), Mohlke, K.L. (Karen), O'ConneL, J.R. (Jeffrey), Peltonen, L. (Leena Johanna), SchleSinger, D. (David), Strachan, D.P. (David), Watanabe, R.M. (Richard), Duijn, C.M. (Cornelia) van, Wichmann, H.E. (Heinz Erich), Frayling, T.M. (Timothy), Thorsteinsdottir, U. (Unnur), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), StefanSon, K. (Kari), North, K.E. (Kari), McArthy, M.I. (Mark), Hirschhorn, J.N. (Joel), IngelSon, E. (Erik), Loos, R.J.F. (Ruth), Weedon, M.N. (Michael), Speliotes, E.K. (Elizabeth), Willer, C.J. (Cristen), Berndt, S.I. (Sonja), Monda, K.L. (Keri), Thorleifsson, G. (Gudmar), Jackson, A.U. (Anne), Allen, H.L., Lindgren, C.M. (Cecilia), Luan, J., Mägi, R. (Reedik), Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Winkler, T.W. (Thomas), Qi, L. (Lu), Workalemahu, T. (Tsegaselassie), Heid, I.M. (Iris), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Wheeler, E. (Eleanor), Wood, A.R. (Andrew), Ferreira, T. (Teresa), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Eestrada, K. (Karol), Liang, L. (Liming), Nemesh, J. (James), Park, J.H., Gustafsson, S. (Stefan), Kilpeläinen, T.O. (Tuomas), Yang, J. (Joanna), Bouatia-Naji, N. (Nabila), Eesko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Kutalik, Z. (Zoltán), Mangino, M. (Massimo), Raychaudhuri, S. (Soumya), Scherag, A. (Andre), Smith, A.V. (Albert Vernon), Welch, R.P. (Ryan), Zhao, J.H. (Jing Hua), Aben, K.K.H. (Katja), Absher, D. (Devin), Amin, N. (Najaf), Dixon, A.L. (Anna), Fisher, E. (Eeva), Glazer, N.L. (Nicole), Goddard, M.E. (Michael), Heard-Costa, N.L. (Nancy), Hoesel, V. (Volker), Hottenga, J.J. (Jouke Jan), Johansson, A. (Åsa), Johnson, T. (Toby), Ketkar, S. (Shamika), Lamina, C. (Claudia), Li, S. (Shengxu), Moffatt, M.F. (Miriam), Myers, R.H. (Richard), Narisu, N. (Narisu), Perry, J.R.B. (John), Peters, M.J. (Marjolein), Preuss, M. (Michael), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Sandholt, C. (Camilla), Scott, L.J. (Laura), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Wingerden, S. (Sophie) van, White, C.C. (Charles), Wiklund, F. (Fredrik), Barlassina, C. (Christina), Chasman, D.I. (Daniel), Cooper, M.N. (Matthew), Jansson, J.O., Lawrence, R.W. (Robert), Pellikka, N. (Niina), Prokopenko, I. (Inga), Shi, J. (Jianxin), Thiering, E. (Eelisabeth), Alavere, H. (Helene), Alibrandi, M.T.S. (Maria), Almgren, P. (Peter), Arnold, A.M. (Alice), Aspelund, T. (Thor), Atwood, L.D. (Larry), Balkau, B. (Beverley), Balmforth, A.J. (Anthony), Bennett, A.J. (Amanda), Ben-Shlomo, Y., Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Biebermann, H. (Heike), Blakemore, A.I.F. (Alexandra), Boes, T. (Tanja), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Buchanan, T.A. (Thomas), Busonero, F., Campbell, H. (Harry), Cappuccio, F.P. (Francesco), Cavalcanti-Proença, C. (Christine), Chen, Y.D.I. (Yii-Der Ida), Chen, C.-M. (Chih-Mei), Chines, P.S. (Peter), Clarke, R., Coin, L. (Lachlan), Connell, J. (John), Day, I.N.M. (Ian), Heijer, M. (Martin) den, Duan, J. (Jubao), Eebrahim, S. (Shah), Eelliott, P. (Paul), Eelosua, R. (Roberto), Eeiriksdottir, G. (Gudny), Eerdos, M.R. (Micheal), Eeriksson, J.G. (Johan), Facheris, M.F. (Maurizio), Felix, S.B. (Stephan), Fischer-Posovszky, P. (Pamela), Folsom, A.R. (Aaron), Friedrich, N. (Nele), Freimer, N.B. (Nelson), Fu, M. (Mao), Gaget, S. (Stefan), Gejman, P.V. (Pablo), Geus, E.J.C. (Eco) de, Gieger, C. (Christian), Gjesing, A.P. (Anette), Goel, A. (Anuj), Goyette, P. (Philippe), Grallert, H. (Harald), Gräßler, J. (Jürgen), Greenawalt, D. (Danielle), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Guiducci, C. (Candace), Hartikainen, A.L., Hassanali, N. (Neelam), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Heath, A.C. (Andrew), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hinney, A. (Anke), Hofman, A. (Albert), Homuth, G. (Georg), Hui, J. (Jennie), Igl, W. (Wilmar), Iribarren, C. (Carlos), Isomaa, B. (Bo), Jacobs, K.B. (Kevin), Jarick, I. (Ivonne), Jewell, E. (Eelizabeth), John, U. (Ulrich), Jørgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaakinen, M. (Marika), Kajantie, E. (Eero), Kaplan, R.C. (Robert), Kathiresan, S. (Sekar), Kettunen, J. (Johannes), Kinnunen, L. (Leena), Knowles, J.W. (Joshua), Kolcic, I. (Ivana), König, I.R. (Inke), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kusisto, J. (Johanna), Kraft, P. (Peter), Kvaløy, K. (Kirsti), Laitinen, J. (Jaana), Lantieri, O. (Olivier), Lanzani, C. (Chiara), Launer, L.J. (Lenore), Lecoeur, C. (Cécile), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Liu, J. (Jianjun), Lokki, M.L., Lorentzon, M. (Mattias), Luben, R.N. (Robert), Ludwig, B. (Barbara), Manunta, P. (Paolo), Marek, D. (Diana), Marre, M. (Michel), Martin, N.G. (Nicholas), McArdle, W.L. (Wendy), McCarthy, M.I. (Mark), McKnight, B. (Barbara), Meitinger, T. (Thomas), Melander, O. (Olle), Meyre, D. (David), Midthjell, K. (Kristian), Montgomery, G.W. (Grant), Morken, M.A. (Mario), Morris, A.D. (Andrew), Mulic, R. (Rosanda), Ngwa, J.S., Nelis, M. (Mari), Neville, M.J. (Matthew), Nyholt, D.R. (Dale), O'Ddonnell, C.J. (Christopher), O'Rahilly, S. (Stephen), Ong, K. (Ken), Oostra, B.A. (Ben), Paré, G. (Guillaume), Parker, A.N. (Alex), Perola, M. (Markus), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Platou, C.P. (Carl), Polasek, O. (Ozren), Pouta, A. (Anneli), Rafelt, S. (Suzanne), Raitakari, O. (Olli), Rayner, N.W. (Nigel William), Ridderstråle, M. (Martin), Rief, W. (Winfried), Ruokonen, A. (Aimo), Robertson, N.R. (Neil), Rzehak, P. (Peter), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Saramies, J. (Jouko), Savolainen, M.J. (Markku), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Silander, K. (Kaisa), Sinisalo, J. (Juha), Siscovick, D.S. (David), Smit, J.H. (Jan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Stephens, J. (Jonathan), Surakka, I. (Ida), Swift, A.J. (Amy), Tammesoo, M.L., Tardif, J.-C. (Jean-Claude), Teder-Laving, M. (Maris), Teslovich, T.M. (Tanya), Thompson, J.R. (John), Thomson, B. (Brian), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Meurs, J.B.J. (Joyce) van, OMen, G.J. van, Vatin, V. (Vincent), Viikari, J. (Jorma), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogel, C.I. (Carla), Voight, B.F. (Benjamin), Waite, L. (Lindsay), Wallaschofski, H. (Henri), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wiegand, S. (Susanna), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witte, D.R. (Deniel), Witteman, J.C.M. (Jacqueline), Xu, J. (Jianfeng), Zhang, Q. (Qunyuan), Zgaga, L. (Lina), Ziegler, A. (Andreas), Zitting, P. (Paavo), Beilby, J.P. (John), FarOqi, I.S. (Ssadaf), Hebebrand, J. (Johannes), Huikuri, H.V. (Heikki), James, A. (Alan), Kähönen, M. (Mika), Levinson, D.F. (Douglas), MacCiardi, F. (Fabio), Nieminen, M.S. (Markku), Ohlsson, C. (Claes), Palmer, C. (Cameron), Ridker, P.M. (Paul), Stumvoll, M. (Michael), Beckmann, J.S. (Jacques), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Collins, F.S. (Francis), Cupples, L.A. (Adrienne), Eerdmann, J. (Jeanette), Frogue, P. (Philippe), Grönberg, H. (Henrik), Gyllensten, U. (Ulf), Hansen, T. (Torben), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayes, R.B. (Richard), Heinrich, J. (Joachim), Hu, F.B. (Frank), Hveem, K. (Kristian), Illig, T. (Thomas), Järvelin, M.R., Kaprio, J. (Jaakko), Karpe, F. (Fredrik), Khaw, K-T. (Kay-Tee), Kiemeney, L.A.L.M. (Bart), Krude, H., Laakso, M. (Markku), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Reinehr, T. (Thomas), Rissanen, A. (Aila), Rudan, I. (Igor), Samani, N.J. (Nilesh), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Spector, T.D. (Timothy), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Valle, T.T. (Timo), Wabitsch, M. (Martin), Waeber, G. (Gérard), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Wright, A.F. (Alan), Zillikens, M.C. (Carola), ChatterjE, N. (Nilanjan), McCarroll, S.A. (Steve), Purcell, S. (Shaun), Schadt, E.E. (Eric), Visscher, P.M. (Peter), Assimes, T.L. (Themistocles), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D.J. (David), Mohlke, K.L. (Karen), O'ConneL, J.R. (Jeffrey), Peltonen, L. (Leena Johanna), SchleSinger, D. (David), Strachan, D.P. (David), Watanabe, R.M. (Richard), Duijn, C.M. (Cornelia) van, Wichmann, H.E. (Heinz Erich), Frayling, T.M. (Timothy), Thorsteinsdottir, U. (Unnur), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), StefanSon, K. (Kari), North, K.E. (Kari), McArthy, M.I. (Mark), Hirschhorn, J.N. (Joel), IngelSon, E. (Erik), Loos, R.J.F. (Ruth), and Weedon, M.N. (Michael)
Abstract: Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS index (P < 5-10-8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly aSociated loci may provide new insights into human body weight regulation.
Published: 2010
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20. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Author: Heid, I.M. (Iris), Jackson, A.U. (Anne), Randall, J.C. (Joshua), Winkler, T.W. (Thomas), Qi, L. (Lu), Ssteinthorsdottir, V. (Valgerdur), Tthorleifsson, G. (Ggudmar), Zillikens, M.C. (Carola), Sspeliotes, E.K. (Eelizabeth), Mägi, R. (Reedik), Workalemahu, T. (Tsegaselassie), White, C.C. (Charles), Bouatia-Naji, N. (Nabila), Harris, T.B. (Tamara), Berndt, S.I. (Sonja), Ingelsson, E. (Erik), Willer, C.J. (Cristen), Luan, J., Vedantam, S. (Sailaja), Eesko, T. (Tõnu), Kilpeläinen, T.O. (Tuomas), Kutalik, Z. (Zoltán), Li, S. (Shengxu), Monda, K.L. (Keri), Dixon, A.L. (Anna), Holmes, C. (Christopher), Kaplan, R.C. (Robert), Liang, L. (Liming), Min, J. (Josine), Moffatt, M.F. (Miriam), Molony, C. (Cliona), Nicholson, G. (Ggeorge), Sschadt, E.E. (Eeric), Zondervan, K.T. (Krina), Feitosa, M.F. (Mary Furlan), Ferreira, T. (Teresa), Allen, H.L., Weyant, R.J. (Robert), Wheeler, E. (Eleanor), Wood, A.R. (Andrew), Eestrada, K. (Karol), Goddard, M.E. (Michael), Lettre, G. (Guillaume), Mangino, M. (Massimo), Nyholt, D.R. (Dale), Purcell, S. (Shaun), Ssmith, A.V., Visscher, P.M. (Peter), Yang, J. (Joanna), McCcarroll, S.A. (Ssteven), Nemesh, J. (James), Voight, B.F. (Benjamin), Absher, D. (Devin), Amin, N. (Najaf), Aspelund, T. (Thor), Coin, L. (Lachlan), Glazer, N.L. (Nicole), Hayward, C. (Caroline), Heard-Ccosta, N. (Nancy), Hottenga, J.J. (Jouke Jan), Johansson, A. (Åsa), Johnson, T. (Toby), Kaakinen, M. (Marika), Kapur, K. (Karen), Ketkar, S. (Shamika), Knowles, J.W. (Joshua), Kraft, P. (Peter), Kraja, A. (Aldi), Lamina, C. (Claudia), Leitzmann, M.F. (Michael), McKknight, B. (Barbara), Morris, A.D. (Andrew), Oong, K. (Ken), Perry, J.R.B. (John), Peters, M.J. (Marjolein), Polasek, O. (Ozren), Prokopenko, I. (Inga), Rayner, N.W. (Nigel William), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Robertson, N.R. (Neil), Sanna, S. (Serena), Sovio, U. (Ulla), Surakka, I. (Ida), Teumer, A. (Alexander), Wingerden, S. (Sophie) van, Vitart, V. (Veronique), Zhao, J.H. (Jing Hua), Cavalcanti-Proença, C. (Christine), Chines, P.S. (Peter), Fisher, E. (Eeva), Kulzer, J.R. (Jennifer), Lecoeur, C. (Cécile), Narisu, N. (Narisu), Sandholt, C. (Camilla), Scott, L.J. (Laura), Silander, K. (Kaisa), Stark, K. (Klaus), Tammesoo, M.L., Teslovich, T.M. (Tanya), Timpson, N.J. (Nicholas), Welch, R.P. (Ryan), Chasman, D.I. (Daniel), Cooper, M.N. (Matthew), Jansson, J.O., Kettunen, J. (Johannes), Wlawrence, R. (Robert), Pellikka, N. (Niina), Perola, M. (Markus), Vandenput, L. (Liesbeth), Alavere, H. (Helene), Almgren, P. (Peter), Atwood, L.D. (Larry), Bennett, A.J. (Amanda), Biffar, R. (Reiner), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan), Buchanan, T.A. (Thomas), Campbell, H. (Harry), Day, I.N.M. (Ian), Dei, M. (Mariano), Dörr, M. (Marcus), Eelliott, P. (Paul), Eerdos, M.R. (Micheal), Eeriksson, J.G. (Johan), Freimer, N.B. (Nelson), Fu, M. (Mao), Gaget, S. (Stefan), Geus, E.J.C. (Eco) de, Gjesing, A.P. (Anette), Grallert, H. (Harald), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Guiducci, C. (Candace), Hartikainen, A.L., Hassanali, N. (Neelam), Havulinna, A.S. (Aki), Herzig, K.H., Hicks, A.A. (Andrew), Hui, J. (Jennie), Igl, W. (Wilmar), Jousilahti, P. (Pekka), Jula, A. (Antti), Kajantie, E. (Eero), Kinnunen, L. (Leena), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kroemer, H.K. (Heyo), Krzelj, V. (Vjekoslav), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Laitinen, J. (Jaana), Lantieri, O. (Olivier), Lathrop, G.M. (Mark), Lokki, M.L., Luben, R.N. (Robert), Ludwig, B. (Barbara), McArdle, W.L. (Wendy), McCcarthy, A. (Anne), Morken, M.A. (Mario), Nelis, M. (Mari), Neville, M.J. (Matthew), Paré, G. (Guillaume), Parker, A.N. (Alex), Peden, J. (John), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Platou, C.P. (Carl), Pouta, A. (Anneli), Ridderstråle, M. (Martin), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sinisalo, J. (Juha), Smit, J.H. (Jan), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather), Swift, A.J. (Amy), Teder-Llaving, M. (Maris), Thomson, B. (Brian), Usala, G., Meurs, J.B.J. (Joyce) van, Ommen, G.J. (Gert) van, Vatin, V. (Vincent), Volpato, C.B., Wallaschofski, H. (Henri), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witte, D.R. (Deniel), Zgaga, L. (Lina), Zitting, P. (Paavo), Beilby, J.P. (John), James, A. (Alan), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Nieminen, M.S. (Markku), Ohlsson, C. (Claes), Palmer, C. (Cameron), Raitakari, O. (Olli), Ridker, P.M. (Paul), Stumvoll, M. (Michael), Tönjes, A. (Anke), Viikari, J. (Jorma), Balkau, B. (Beverley), Ben-Shlomo, Y., Bergman, R.N. (Richard), Boeing, H. (Heiner), Smith, A.V. (Albert Vernon), Eebrahim, S. (Shah), Froguel, P. (Philippe), Hansen, T. (Torben), Hengstenberg, C. (Christian), Hveem, K. (Kristian), Isomaa, B. (Bo), Jørgensen, T. (Torben), Karpe, F. (Fredrik), Khaw, K-T. (Kay-Tee), Laakso, M. (Markku), Lawlor, D.A. (Debbie), Marre, M. (Michel), Meitinger, T. (Thomas), Metspalu, A. (Andres), Midthjell, K. (Kristian), Pedersen, O. (Oluf), Salomaa, V. (Veikko), Schwarz, P.E.H. (Peter), Tuomi, T. (Tiinamaija), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Wareham, N.J. (Nick), Arnold, A.M. (Alice), Beckmann, J.S. (Jacques), Bergmann, S.M. (Sven), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Collins, F.S. (Francis), Eeiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Hattersley, A.T. (Andrew), Hofman, A. (Albert), Hu, F.B. (Frank), Illig, T. (Thomas), Iribarren, C. (Carlos), Järvelin, M.R., Kao, W.H.L. (Wen), Kaprio, J. (Jaakko), Launer, L.J. (Lenore), Munroe, P. (Patricia), Oostra, B.A. (Ben), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rissanen, A. (Aila), Rudan, I. (Igor), Shuldiner, A.R. (Alan), Soranzo, N. (Nicole), Spector, T.D. (Timothy), Syvanen, A.C., Uda, M. (Manuela), Uitterlinden, A.G. (André), Völzke, H. (Henry), Vollenweider, P. (Peter), Wilson, J.F. (James), Witteman, J.C.M. (Jacqueline), Wright, A.F. (Alan), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Frayling, T.M. (Timothy), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D.J. (David), North, K.E. (Kari), O'Cconnell, J.R. (Jeffrey), Peltonen, L. (Leena Johanna), Schlessinger, D., Strachan, D.P. (David), Hirschhorn, J.N. (Joel), Assimes, T.L. (Themistocles), Wichmann, H.E. (Heinz Erich), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Stefansson, K. (Kari), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), Barroso, I.E. (Inês), Fox, C.S. (Caroline), Mohlke, K.L. (Karen), Lindgren, C.M. (Cecilia), Watanabe, R.M. (Richard), Weedon, M.N. (Michael), Heid, I.M. (Iris), Jackson, A.U. (Anne), Randall, J.C. (Joshua), Winkler, T.W. (Thomas), Qi, L. (Lu), Ssteinthorsdottir, V. (Valgerdur), Tthorleifsson, G. (Ggudmar), Zillikens, M.C. (Carola), Sspeliotes, E.K. (Eelizabeth), Mägi, R. (Reedik), Workalemahu, T. (Tsegaselassie), White, C.C. (Charles), Bouatia-Naji, N. (Nabila), Harris, T.B. (Tamara), Berndt, S.I. (Sonja), Ingelsson, E. (Erik), Willer, C.J. (Cristen), Luan, J., Vedantam, S. (Sailaja), Eesko, T. (Tõnu), Kilpeläinen, T.O. (Tuomas), Kutalik, Z. (Zoltán), Li, S. (Shengxu), Monda, K.L. (Keri), Dixon, A.L. (Anna), Holmes, C. (Christopher), Kaplan, R.C. (Robert), Liang, L. (Liming), Min, J. (Josine), Moffatt, M.F. (Miriam), Molony, C. (Cliona), Nicholson, G. (Ggeorge), Sschadt, E.E. (Eeric), Zondervan, K.T. (Krina), Feitosa, M.F. (Mary Furlan), Ferreira, T. (Teresa), Allen, H.L., Weyant, R.J. (Robert), Wheeler, E. (Eleanor), Wood, A.R. (Andrew), Eestrada, K. (Karol), Goddard, M.E. (Michael), Lettre, G. (Guillaume), Mangino, M. (Massimo), Nyholt, D.R. (Dale), Purcell, S. (Shaun), Ssmith, A.V., Visscher, P.M. (Peter), Yang, J. (Joanna), McCcarroll, S.A. (Ssteven), Nemesh, J. (James), Voight, B.F. (Benjamin), Absher, D. (Devin), Amin, N. (Najaf), Aspelund, T. (Thor), Coin, L. (Lachlan), Glazer, N.L. (Nicole), Hayward, C. (Caroline), Heard-Ccosta, N. (Nancy), Hottenga, J.J. (Jouke Jan), Johansson, A. (Åsa), Johnson, T. (Toby), Kaakinen, M. (Marika), Kapur, K. (Karen), Ketkar, S. (Shamika), Knowles, J.W. (Joshua), Kraft, P. (Peter), Kraja, A. (Aldi), Lamina, C. (Claudia), Leitzmann, M.F. (Michael), McKknight, B. (Barbara), Morris, A.D. (Andrew), Oong, K. (Ken), Perry, J.R.B. (John), Peters, M.J. (Marjolein), Polasek, O. (Ozren), Prokopenko, I. (Inga), Rayner, N.W. (Nigel William), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Robertson, N.R. (Neil), Sanna, S. (Serena), Sovio, U. (Ulla), Surakka, I. (Ida), Teumer, A. (Alexander), Wingerden, S. (Sophie) van, Vitart, V. (Veronique), Zhao, J.H. (Jing Hua), Cavalcanti-Proença, C. (Christine), Chines, P.S. (Peter), Fisher, E. (Eeva), Kulzer, J.R. (Jennifer), Lecoeur, C. (Cécile), Narisu, N. (Narisu), Sandholt, C. (Camilla), Scott, L.J. (Laura), Silander, K. (Kaisa), Stark, K. (Klaus), Tammesoo, M.L., Teslovich, T.M. (Tanya), Timpson, N.J. (Nicholas), Welch, R.P. (Ryan), Chasman, D.I. (Daniel), Cooper, M.N. (Matthew), Jansson, J.O., Kettunen, J. (Johannes), Wlawrence, R. (Robert), Pellikka, N. (Niina), Perola, M. (Markus), Vandenput, L. (Liesbeth), Alavere, H. (Helene), Almgren, P. (Peter), Atwood, L.D. (Larry), Bennett, A.J. (Amanda), Biffar, R. (Reiner), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan), Buchanan, T.A. (Thomas), Campbell, H. (Harry), Day, I.N.M. (Ian), Dei, M. (Mariano), Dörr, M. (Marcus), Eelliott, P. (Paul), Eerdos, M.R. (Micheal), Eeriksson, J.G. (Johan), Freimer, N.B. (Nelson), Fu, M. (Mao), Gaget, S. (Stefan), Geus, E.J.C. (Eco) de, Gjesing, A.P. (Anette), Grallert, H. (Harald), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Guiducci, C. (Candace), Hartikainen, A.L., Hassanali, N. (Neelam), Havulinna, A.S. (Aki), Herzig, K.H., Hicks, A.A. (Andrew), Hui, J. (Jennie), Igl, W. (Wilmar), Jousilahti, P. (Pekka), Jula, A. (Antti), Kajantie, E. (Eero), Kinnunen, L. (Leena), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kroemer, H.K. (Heyo), Krzelj, V. (Vjekoslav), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Laitinen, J. (Jaana), Lantieri, O. (Olivier), Lathrop, G.M. (Mark), Lokki, M.L., Luben, R.N. (Robert), Ludwig, B. (Barbara), McArdle, W.L. (Wendy), McCcarthy, A. (Anne), Morken, M.A. (Mario), Nelis, M. (Mari), Neville, M.J. (Matthew), Paré, G. (Guillaume), Parker, A.N. (Alex), Peden, J. (John), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Platou, C.P. (Carl), Pouta, A. (Anneli), Ridderstråle, M. (Martin), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sinisalo, J. (Juha), Smit, J.H. (Jan), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather), Swift, A.J. (Amy), Teder-Llaving, M. (Maris), Thomson, B. (Brian), Usala, G., Meurs, J.B.J. (Joyce) van, Ommen, G.J. (Gert) van, Vatin, V. (Vincent), Volpato, C.B., Wallaschofski, H. (Henri), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witte, D.R. (Deniel), Zgaga, L. (Lina), Zitting, P. (Paavo), Beilby, J.P. (John), James, A. (Alan), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Nieminen, M.S. (Markku), Ohlsson, C. (Claes), Palmer, C. (Cameron), Raitakari, O. (Olli), Ridker, P.M. (Paul), Stumvoll, M. (Michael), Tönjes, A. (Anke), Viikari, J. (Jorma), Balkau, B. (Beverley), Ben-Shlomo, Y., Bergman, R.N. (Richard), Boeing, H. (Heiner), Smith, A.V. (Albert Vernon), Eebrahim, S. (Shah), Froguel, P. (Philippe), Hansen, T. (Torben), Hengstenberg, C. (Christian), Hveem, K. (Kristian), Isomaa, B. (Bo), Jørgensen, T. (Torben), Karpe, F. (Fredrik), Khaw, K-T. (Kay-Tee), Laakso, M. (Markku), Lawlor, D.A. (Debbie), Marre, M. (Michel), Meitinger, T. (Thomas), Metspalu, A. (Andres), Midthjell, K. (Kristian), Pedersen, O. (Oluf), Salomaa, V. (Veikko), Schwarz, P.E.H. (Peter), Tuomi, T. (Tiinamaija), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Wareham, N.J. (Nick), Arnold, A.M. (Alice), Beckmann, J.S. (Jacques), Bergmann, S.M. (Sven), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Collins, F.S. (Francis), Eeiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Hattersley, A.T. (Andrew), Hofman, A. (Albert), Hu, F.B. (Frank), Illig, T. (Thomas), Iribarren, C. (Carlos), Järvelin, M.R., Kao, W.H.L. (Wen), Kaprio, J. (Jaakko), Launer, L.J. (Lenore), Munroe, P. (Patricia), Oostra, B.A. (Ben), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rissanen, A. (Aila), Rudan, I. (Igor), Shuldiner, A.R. (Alan), Soranzo, N. (Nicole), Spector, T.D. (Timothy), Syvanen, A.C., Uda, M. (Manuela), Uitterlinden, A.G. (André), Völzke, H. (Henry), Vollenweider, P. (Peter), Wilson, J.F. (James), Witteman, J.C.M. (Jacqueline), Wright, A.F. (Alan), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Frayling, T.M. (Timothy), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D.J. (David), North, K.E. (Kari), O'Cconnell, J.R. (Jeffrey), Peltonen, L. (Leena Johanna), Schlessinger, D., Strachan, D.P. (David), Hirschhorn, J.N. (Joel), Assimes, T.L. (Themistocles), Wichmann, H.E. (Heinz Erich), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Stefansson, K. (Kari), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), Barroso, I.E. (Inês), Fox, C.S. (Caroline), Mohlke, K.L. (Karen), Lindgren, C.M. (Cecilia), Watanabe, R.M. (Richard), and Weedon, M.N. (Michael)
Abstract: Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
Published: 2010
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21. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Author: Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Randall, J.C. (Joshua), Lamina, C. (Claudia), Steinthorsdottir, V. (Valgerdur), Qi, L. (Lu), Speliotes, E.K. (Elizabeth), Thorleifsson, G. (Gudmar), Willer, C.J. (Cristen), Herrera, B.M. (Blanca), Jackson, A.U. (Anne), Lim, N. (Noha), Scheet, P. (Paul), Soranzo, N. (Nicole), Amin, N. (Najaf), Aulchenko, Y.S. (Yurii), Chambers, J.C. (John), Drong, A. (Alexander), Luan, J., Lyon, H.N. (Helen), Rivadeneira Ramirez, F. (Fernando), Sanna, S. (Serena), Timpson, N.J. (Nicholas), Zillikens, M.C. (Carola), Jing, H.Z., Almgren, P. (Peter), Bandinelli, S. (Stefania), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bonnycastle, L.L. (Lori), Bumpstead, S. (Suzannah), Chanock, S.J. (Stephen), Cherkas, L. (Lynn), Chines, P.S. (Peter), Coin, L. (Lachlan), Cooper, C. (Charles), Crawford, G. (Gabe), Doering, A. (Angela), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ebrahim, S. (Shanil), Elliott, P. (Paul), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Ferrucci, L. (Luigi), Fischer, G. (Guido), Forouhi, N.G. (Nita), Gieger, C. (Christian), Grallert, H. (Harald), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Guiducci, C. (Candace), Hadley, D. (David), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hofman, A. (Albert), Holle, R. (Rolf), Holloway, J.W. (John), Illig, T. (Thomas), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jameson, K. (Karen), Jousilahti, P. (Pekka), Karpe, F. (Fredrik), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Morken, M.A. (Mario), Morris, A.P. (Andrew), Munroe, P. (Patricia), Narisu, N. (Narisu), Nordström, A. (Anna), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Payne, F. (Felicity), Peden, J. (John), Prokopenko, I. (Inga), Renström, F. (Frida), Ruokonen, A. (Aimo), Salomaa, V. (Veikko), Sandhu, M.S. (Manjinder), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Song, K. (Kijoung), Yuan, X. (Xin), Stringham, H.M. (Heather), Swift, A.J. (Amy), Tuomi, T. (Tiinamaija), Uda, M. (Manuela), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Walters, G.B. (Bragi), Weedon, M.N. (Michael), Witteman, J.C.M. (Jacqueline), Zhang, C. (Cuilin), Caulfield, M. (Mark), Collins, F.S. (Francis), Smith, A.V. (Davey), Day, I.N.M. (Ian), Franks, P.W. (Paul), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Kong, A. (Augustine), Kooner, J.S. (Jaspal), Laakso, M. (Markku), Lakatta, E. (Edward), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Strachan, D.P. (David), Tanaka, T. (Toshiko), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wareham, N.J. (Nick), Watkins, H. (Hugh), Waterworth, D. (Dawn), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Groop, L. (Leif), Hunter, D.J. (David), Thorsteinsdottir, U. (Unnur), Schlessinger, D. (David), Wichmann, H.E. (Erich), Frayling, T.M. (Timothy), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Loos, R.J.F. (Ruth), Zwart, J-A. (John-Anker), Mohlke, K.L. (Karen), Barroso, I.E. (Inês), McCarthy, M.I. (Mark), Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Randall, J.C. (Joshua), Lamina, C. (Claudia), Steinthorsdottir, V. (Valgerdur), Qi, L. (Lu), Speliotes, E.K. (Elizabeth), Thorleifsson, G. (Gudmar), Willer, C.J. (Cristen), Herrera, B.M. (Blanca), Jackson, A.U. (Anne), Lim, N. (Noha), Scheet, P. (Paul), Soranzo, N. (Nicole), Amin, N. (Najaf), Aulchenko, Y.S. (Yurii), Chambers, J.C. (John), Drong, A. (Alexander), Luan, J., Lyon, H.N. (Helen), Rivadeneira Ramirez, F. (Fernando), Sanna, S. (Serena), Timpson, N.J. (Nicholas), Zillikens, M.C. (Carola), Jing, H.Z., Almgren, P. (Peter), Bandinelli, S. (Stefania), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bonnycastle, L.L. (Lori), Bumpstead, S. (Suzannah), Chanock, S.J. (Stephen), Cherkas, L. (Lynn), Chines, P.S. (Peter), Coin, L. (Lachlan), Cooper, C. (Charles), Crawford, G. (Gabe), Doering, A. (Angela), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ebrahim, S. (Shanil), Elliott, P. (Paul), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Ferrucci, L. (Luigi), Fischer, G. (Guido), Forouhi, N.G. (Nita), Gieger, C. (Christian), Grallert, H. (Harald), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Guiducci, C. (Candace), Hadley, D. (David), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hofman, A. (Albert), Holle, R. (Rolf), Holloway, J.W. (John), Illig, T. (Thomas), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jameson, K. (Karen), Jousilahti, P. (Pekka), Karpe, F. (Fredrik), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Morken, M.A. (Mario), Morris, A.P. (Andrew), Munroe, P. (Patricia), Narisu, N. (Narisu), Nordström, A. (Anna), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Payne, F. (Felicity), Peden, J. (John), Prokopenko, I. (Inga), Renström, F. (Frida), Ruokonen, A. (Aimo), Salomaa, V. (Veikko), Sandhu, M.S. (Manjinder), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Song, K. (Kijoung), Yuan, X. (Xin), Stringham, H.M. (Heather), Swift, A.J. (Amy), Tuomi, T. (Tiinamaija), Uda, M. (Manuela), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Walters, G.B. (Bragi), Weedon, M.N. (Michael), Witteman, J.C.M. (Jacqueline), Zhang, C. (Cuilin), Caulfield, M. (Mark), Collins, F.S. (Francis), Smith, A.V. (Davey), Day, I.N.M. (Ian), Franks, P.W. (Paul), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Kong, A. (Augustine), Kooner, J.S. (Jaspal), Laakso, M. (Markku), Lakatta, E. (Edward), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Strachan, D.P. (David), Tanaka, T. (Toshiko), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wareham, N.J. (Nick), Watkins, H. (Hugh), Waterworth, D. (Dawn), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Groop, L. (Leif), Hunter, D.J. (David), Thorsteinsdottir, U. (Unnur), Schlessinger, D. (David), Wichmann, H.E. (Erich), Frayling, T.M. (Timothy), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Loos, R.J.F. (Ruth), Zwart, J-A. (John-Anker), Mohlke, K.L. (Karen), Barroso, I.E. (Inês), and McCarthy, M.I. (Mark)
Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102-11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10-8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human
Published: 2009
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22. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Author: Willer, C.J. (Cristen), Speliotes, E.K. (Elizabeth), Loos, R.J.F. (Ruth), Li, S. (Shengxu), Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Berndt, S.I. (Sonja), Elliott, A.L. (Amanda), Jackson, A.U. (Anne), Lamina, C. (Claudia), Lettre, G. (Guillaume), Lim, N. (Noha), Lyon, H.N. (Helen), McCarroll, S.A. (Steven), Papadakis, K. (Konstantinos), Qi, L. (Lu), Randall, J.C. (Joshua), Roccasecca, R.M., Sanna, S. (Serena), Scheet, P. (Paul), Weedon, M.N. (Michael), Wheeler, E. (Eleanor), Zhao, J.H. (Jing Hua), Jacobs, L.C. (Leonie), Prokopenko, I. (Inga), Soranzo, N. (Nicole), Tanaka, T. (Toshiko), Timpson, N.J. (Nicholas), Almgren, P. (Peter), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bingham, S. (Sheila), Bonnycastle, L.L. (Lori), Brown, M.J. (Morris), Burtt, N.P. (Noël), Chines, P.S. (Peter), Coin, L. (Lachlan), Collins, F.S. (Francis), Connell, J. (John), Cooper, C. (Charles), Smith, A.V. (Davey), Dennison, E.M. (Elaine), Deodhar, P. (Parimal), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Evans, D.M. (David), Gianniny, L. (Lauren), Gieger, C. (Christian), Gillson, C.J. (Christopher), Guiducci, C. (Candace), Hackett, R. (Rachel), Hadley, D. (David), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hebebrand, J. (Johannes), Hofman, A. (Albert), Isomaa, B. (Bo), Johnson, T. (Toby), Jousilahti, P. (Pekka), Jovanovic, Z. (Zorica), Khaw, K-T. (Kay-Tee), Kraft, P. (Peter), Kuokkanen, M. (Mikko), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lakatta, E. (Edward), Luan, J., Luben, R.N. (Robert), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Mulas, A. (Antonella), Munroe, P. (Patricia), Narisu, N. (Narisu), Ness, A.R. (Andrew), Northstone, K. (Kate), O'Rahilly, S. (Stephen), Purmann, C. (Carolin), Rees, M.G. (Matthew), Ridderstråle, M. (Martin), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Sandhu, M.S. (Manjinder), Saramies, J. (Jouko), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Sims, M.A. (Matthew), Song, K. (Kijoung), Stephens, J. (Jonathan), Stevens, S. (Suzanne), Stringham, H.M. (Heather), Tung, Y.C.L. (Loraine), Valle, T.T. (Timo), Tikka-Kleemola, P. (Päivi), Vimaleswaran, K.S. (Karani), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Watanabe, R.M. (Richard), Waterworth, D. (Dawn), Watkins, N. (Nicholas), Witteman, J.C.M. (Jacqueline), Zeggini, E. (Eleftheria), Zhai, G. (Guangju), Zillikens, M.C. (Carola), Altshuler, D. (David), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Farooqi, I.S. (Sadaf), Ferrucci, L. (Luigi), Guralnik, J.M. (Jack), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Laakso, M. (Markku), Mooser, V. (Vincent), Ong, K.K. (Ken), Ouwehand, W.H. (Willem), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Tuomi, T. (Tiinamaija), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Deloukas, P. (Panagiotis), Wareham, N.J. (Nick), Frayling, T.M. (Timothy), Groop, L. (Leif), Hayes, R.B. (Richard), Hunter, D. (David), Mohlke, K.L. (Karen), Peltonen, L. (Leena Johanna), Schlessinger, D. (David), Strachan, D.P. (David), Wichmann, H.E. (Erich), McCarthy, M.I. (Mark), Boehnke, M. (Michael), Barroso, I.E. (Inês), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Willer, C.J. (Cristen), Speliotes, E.K. (Elizabeth), Loos, R.J.F. (Ruth), Li, S. (Shengxu), Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Berndt, S.I. (Sonja), Elliott, A.L. (Amanda), Jackson, A.U. (Anne), Lamina, C. (Claudia), Lettre, G. (Guillaume), Lim, N. (Noha), Lyon, H.N. (Helen), McCarroll, S.A. (Steven), Papadakis, K. (Konstantinos), Qi, L. (Lu), Randall, J.C. (Joshua), Roccasecca, R.M., Sanna, S. (Serena), Scheet, P. (Paul), Weedon, M.N. (Michael), Wheeler, E. (Eleanor), Zhao, J.H. (Jing Hua), Jacobs, L.C. (Leonie), Prokopenko, I. (Inga), Soranzo, N. (Nicole), Tanaka, T. (Toshiko), Timpson, N.J. (Nicholas), Almgren, P. (Peter), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bingham, S. (Sheila), Bonnycastle, L.L. (Lori), Brown, M.J. (Morris), Burtt, N.P. (Noël), Chines, P.S. (Peter), Coin, L. (Lachlan), Collins, F.S. (Francis), Connell, J. (John), Cooper, C. (Charles), Smith, A.V. (Davey), Dennison, E.M. (Elaine), Deodhar, P. (Parimal), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Evans, D.M. (David), Gianniny, L. (Lauren), Gieger, C. (Christian), Gillson, C.J. (Christopher), Guiducci, C. (Candace), Hackett, R. (Rachel), Hadley, D. (David), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hebebrand, J. (Johannes), Hofman, A. (Albert), Isomaa, B. (Bo), Johnson, T. (Toby), Jousilahti, P. (Pekka), Jovanovic, Z. (Zorica), Khaw, K-T. (Kay-Tee), Kraft, P. (Peter), Kuokkanen, M. (Mikko), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lakatta, E. (Edward), Luan, J., Luben, R.N. (Robert), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Mulas, A. (Antonella), Munroe, P. (Patricia), Narisu, N. (Narisu), Ness, A.R. (Andrew), Northstone, K. (Kate), O'Rahilly, S. (Stephen), Purmann, C. (Carolin), Rees, M.G. (Matthew), Ridderstråle, M. (Martin), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Sandhu, M.S. (Manjinder), Saramies, J. (Jouko), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Sims, M.A. (Matthew), Song, K. (Kijoung), Stephens, J. (Jonathan), Stevens, S. (Suzanne), Stringham, H.M. (Heather), Tung, Y.C.L. (Loraine), Valle, T.T. (Timo), Tikka-Kleemola, P. (Päivi), Vimaleswaran, K.S. (Karani), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Watanabe, R.M. (Richard), Waterworth, D. (Dawn), Watkins, N. (Nicholas), Witteman, J.C.M. (Jacqueline), Zeggini, E. (Eleftheria), Zhai, G. (Guangju), Zillikens, M.C. (Carola), Altshuler, D. (David), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Farooqi, I.S. (Sadaf), Ferrucci, L. (Luigi), Guralnik, J.M. (Jack), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Laakso, M. (Markku), Mooser, V. (Vincent), Ong, K.K. (Ken), Ouwehand, W.H. (Willem), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Tuomi, T. (Tiinamaija), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Deloukas, P. (Panagiotis), Wareham, N.J. (Nick), Frayling, T.M. (Timothy), Groop, L. (Leif), Hayes, R.B. (Richard), Hunter, D. (David), Mohlke, K.L. (Karen), Peltonen, L. (Leena Johanna), Schlessinger, D. (David), Strachan, D.P. (David), Wichmann, H.E. (Erich), McCarthy, M.I. (Mark), Boehnke, M. (Michael), Barroso, I.E. (Inês), Abecasis, G.R. (Gonçalo), and Hirschhorn, J.N. (Joel)
Abstract: Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10-8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
Published: 2009
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23. Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 h.

Author: Grenko CM, Taylor HJ, Bonnycastle LL, Xue D, Lee BN, Weiss Z, Yan T, Swift AJ, Mansell EC, Lee A, Robertson CC, Narisu N, Erdos MR, Chen S, Collins FS, and Taylor DL
Subjects: Humans, Transcriptome, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Insulin metabolism, Insulin-Secreting Cells metabolism, Insulin-Secreting Cells drug effects, Hyperglycemia genetics, Hyperglycemia metabolism, Islets of Langerhans metabolism, Islets of Langerhans drug effects, Glucose pharmacology, Glucose metabolism, Single-Cell Analysis, Gene Expression Profiling
Abstract: Aims/hypothesis: Disruption of pancreatic islet function and glucose homeostasis can lead to the development of sustained hyperglycaemia, beta cell glucotoxicity and subsequently type 2 diabetes. In this study, we explored the effects of in vitro hyperglycaemic conditions on human pancreatic islet gene expression across 24 h in six pancreatic cell types: alpha; beta; gamma; delta; ductal; and acinar. We hypothesised that genes associated with hyperglycaemic conditions may be relevant to the onset and progression of diabetes., Methods: We exposed human pancreatic islets from two donors to low (2.8 mmol/l) and high (15.0 mmol/l) glucose concentrations over 24 h in vitro. To assess the transcriptome, we performed single-cell RNA-seq (scRNA-seq) at seven time points. We modelled time as both a discrete and continuous variable to determine momentary and longitudinal changes in transcription associated with islet time in culture or glucose exposure. Additionally, we integrated genomic features and genetic summary statistics to nominate candidate effector genes. For three of these genes, we functionally characterised the effect on insulin production and secretion using CRISPR interference to knock down gene expression in EndoC-βH1 cells, followed by a glucose-stimulated insulin secretion assay., Results: In the discrete time models, we identified 1344 genes associated with time and 668 genes associated with glucose exposure across all cell types and time points. In the continuous time models, we identified 1311 genes associated with time, 345 genes associated with glucose exposure and 418 genes associated with interaction effects between time and glucose across all cell types. By integrating these expression profiles with summary statistics from genetic association studies, we identified 2449 candidate effector genes for type 2 diabetes, HbA 1c , random blood glucose and fasting blood glucose. Of these candidate effector genes, we showed that three (ERO1B, HNRNPA2B1 and RHOBTB3) exhibited an effect on glucose-stimulated insulin production and secretion in EndoC-βH1 cells., Conclusions/interpretation: The findings of our study provide an in-depth characterisation of the 24 h transcriptomic response of human pancreatic islets to glucose exposure at a single-cell resolution. By integrating differentially expressed genes with genetic signals for type 2 diabetes and glucose-related traits, we provide insights into the molecular mechanisms underlying glucose homeostasis. Finally, we provide functional evidence to support the role of three candidate effector genes in insulin secretion and production., Data Availability: The scRNA-seq data from the 24 h glucose exposure experiment performed in this study are available in the database of Genotypes and Phenotypes (dbGap; https://www.ncbi.nlm.nih.gov/gap/ ) with accession no. phs001188.v3.p1. Study metadata and summary statistics for the differential expression, gene set enrichment and candidate effector gene prediction analyses are available in the Zenodo data repository ( https://zenodo.org/ ) under accession number 11123248. The code used in this study is publicly available at https://github.com/CollinsLabBioComp/publication-islet_glucose_timecourse ., (© 2024. The Author(s).)
Published: 2024
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24. Scalable Hypothalamic Arcuate Neuron Differentiation from Human Pluripotent Stem Cells Suitable for Modeling Metabolic and Reproductive Disorders.

Author: Jovanovic VM, Narisu N, Bonnycastle LL, Tharakan R, Mesch KT, Glover HJ, Yan T, Sinha N, Sen C, Castellano D, Yang S, Blivis D, Ryu S, Bennett DF, Rosales-Soto G, Inman J, Ormanoglu P, LeClair CA, Xia M, Schneider M, Hernandez-Ochoa EO, Erdos MR, Simeonov A, Chen S, Collins FS, Doege CA, and Tristan CA
Abstract: The hypothalamus, composed of several nuclei, is essential for maintaining our body's homeostasis. The arcuate nucleus (ARC), located in the mediobasal hypothalamus, contains neuronal populations with eminent roles in energy and glucose homeostasis as well as reproduction. These neuronal populations are of great interest for translational research. To fulfill this promise, we used a robotic cell culture platform to provide a scalable and chemically defined approach for differentiating human pluripotent stem cells (hPSCs) into pro-opiomelanocortin (POMC), somatostatin (SST), tyrosine hydroxylase (TH) and gonadotropin-releasing hormone (GnRH) neuronal subpopulations with an ARC-like signature. This robust approach is reproducible across several distinct hPSC lines and exhibits a stepwise induction of key ventral diencephalon and ARC markers in transcriptomic profiling experiments. This is further corroborated by direct comparison to human fetal hypothalamus, and the enriched expression of genes implicated in obesity and type 2 diabetes (T2D). Genome-wide chromatin accessibility profiling by ATAC-seq identified accessible regulatory regions that can be utilized to predict candidate enhancers related to metabolic disorders and hypothalamic development. In depth molecular, cellular, and functional experiments unveiled the responsiveness of the hPSC-derived hypothalamic neurons to hormonal stimuli, such as insulin, neuropeptides including kisspeptin, and incretin mimetic drugs such as Exendin-4, highlighting their potential utility as physiologically relevant cellular models for disease studies. In addition, differential glucose and insulin treatments uncovered adaptability within the generated ARC neurons in the dynamic regulation of POMC and insulin receptors. In summary, the establishment of this model represents a novel, chemically defined, and scalable platform for manufacturing large numbers of hypothalamic arcuate neurons and serves as a valuable resource for modeling metabolic and reproductive disorders., Competing Interests: Conflict of Interest Statement The authors declare no competing interests.
Published: 2024
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25. Generation of Human Isogenic Induced Pluripotent Stem Cell Lines with CRISPR Prime Editing.

Author: Bonnycastle LL, Swift AJ, Mansell EC, Lee A, Winnicki E, Li ES, Robertson CC, Parsons VA, Huynh T, Krilow C, Mohlke KL, Erdos MR, Narisu N, and Collins FS
Subjects: Humans, Clustered Regularly Interspaced Short Palindromic Repeats genetics, CRISPR-Cas Systems genetics, Gene Editing, RNA, Guide, CRISPR-Cas Systems, Diabetes Mellitus, Type 2, Induced Pluripotent Stem Cells
Abstract: We developed an efficient CRISPR prime editing protocol and generated isogenic-induced pluripotent stem cell (iPSC) lines carrying heterozygous or homozygous alleles for putatively causal single nucleotide variants at six type 2 diabetes loci ( ABCC8 , MTNR1B , TCF7L2 , HNF4A , CAMK1D , and GCK ). Our two-step sequence-based approach to first identify transfected cell pools with the highest fraction of edited cells significantly reduced the downstream efforts to isolate single clones of edited cells. We found that prime editing can make targeted genetic changes in iPSC and optimization of system components and guide RNA designs that were critical to achieve acceptable efficiency. Systems utilizing PEmax, epegRNA modifications, and MLH1dn provided significant benefit, producing editing efficiencies of 36-73%. Editing success and pegRNA design optimization required for each variant differed depending on the sequence at the target site. With attention to design, prime editing is a promising approach to generate isogenic iPSC lines, enabling the study of specific genetic changes in a common genetic background.
Published: 2024
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26. Population-scale skeletal muscle single-nucleus multi-omic profiling reveals extensive context specific genetic regulation.

Author: Varshney A, Manickam N, Orchard P, Tovar A, Zhang Z, Feng F, Erdos MR, Narisu N, Ventresca C, Nishino K, Rai V, Stringham HM, Jackson AU, Tamsen T, Gao C, Yang M, Koues OI, Welch JD, Burant CF, Williams LK, Jenkinson C, DeFronzo RA, Norton L, Saramies J, Lakka TA, Laakso M, Tuomilehto J, Mohlke KL, Kitzman JO, Koistinen HA, Liu J, Boehnke M, Collins FS, Scott LJ, and Parker SCJ
Abstract: Skeletal muscle, the largest human organ by weight, is relevant to several polygenic metabolic traits and diseases including type 2 diabetes (T2D). Identifying genetic mechanisms underlying these traits requires pinpointing the relevant cell types, regulatory elements, target genes, and causal variants. Here, we used genetic multiplexing to generate population-scale single nucleus (sn) chromatin accessibility (snATAC-seq) and transcriptome (snRNA-seq) maps across 287 frozen human skeletal muscle biopsies representing 456,880 nuclei. We identified 13 cell types that collectively represented 983,155 ATAC summits. We integrated genetic variation to discover 6,866 expression quantitative trait loci (eQTL) and 100,928 chromatin accessibility QTL (caQTL) (5% FDR) across the five most abundant cell types, cataloging caQTL peaks that atlas-level snATAC maps often miss. We identified 1,973 eGenes colocalized with caQTL and used mediation analyses to construct causal directional maps for chromatin accessibility and gene expression. 3,378 genome-wide association study (GWAS) signals across 43 relevant traits colocalized with sn-e/caQTL, 52% in a cell-specific manner. 77% of GWAS signals colocalized with caQTL and not eQTL, highlighting the critical importance of population-scale chromatin profiling for GWAS functional studies. GWAS-caQTL colocalization showed distinct cell-specific regulatory paradigms. For example, a C2CD4A/B T2D GWAS signal colocalized with caQTL in muscle fibers and multiple chromatin loop models nominated VPS13C , a glucose uptake gene. Sequence of the caQTL peak overlapping caSNP rs7163757 showed allelic regulatory activity differences in a human myocyte cell line massively parallel reporter assay. These results illuminate the genetic regulatory architecture of human skeletal muscle at high-resolution epigenomic, transcriptomic, and cell state scales and serve as a template for population-scale multi-omic mapping in complex tissues and traits., Competing Interests: 4.30 Competing interests SCJP has a research grant from Pfizer.
Published: 2023
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27. Functional interrogation of twenty type 2 diabetes-associated genes using isogenic human embryonic stem cell-derived β-like cells.

Author: Xue D, Narisu N, Taylor DL, Zhang M, Grenko C, Taylor HJ, Yan T, Tang X, Sinha N, Zhu J, Vandana JJ, Nok Chong AC, Lee A, Mansell EC, Swift AJ, Erdos MR, Zhong A, Bonnycastle LL, Zhou T, Chen S, and Collins FS
Subjects: Humans, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Carbonyl Reductase (NADPH) genetics, Carbonyl Reductase (NADPH) metabolism, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Human Embryonic Stem Cells metabolism, Insulin-Secreting Cells metabolism
Abstract: Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional roles of many loci remain unexplored. Here, we engineered isogenic knockout human embryonic stem cell lines for 20 genes associated with T2D risk. We examined the impacts of each knockout on β cell differentiation, functions, and survival. We generated gene expression and chromatin accessibility profiles on β cells derived from each knockout line. Analyses of T2D-association signals overlapping HNF4A-dependent ATAC peaks identified a likely causal variant at the FAIM2 T2D-association signal. Additionally, the integrative association analyses identified four genes (CP, RNASE1, PCSK1N, and GSTA2) associated with insulin production, and two genes (TAGLN3 and DHRS2) associated with β cell sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental line and identified a single likely functional variant at each of 23 T2D-association signals., Competing Interests: Declaration of interests S.C. is the co-founder of OncoBeat, LLC and a consultant of Vesalius Therapeutics., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2023
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28. Adipose tissue eQTL meta-analysis reveals the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits.

Author: Brotman SM, El-Sayed Moustafa JS, Guan L, Broadaway KA, Wang D, Jackson AU, Welch R, Currin KW, Tomlinson M, Vadlamudi S, Stringham HM, Roberts AL, Lakka TA, Oravilahti A, Silva LF, Narisu N, Erdos MR, Yan T, Bonnycastle LL, Raulerson CK, Raza Y, Yan X, Parker SCJ, Kuusisto J, Pajukanta P, Tuomilehto J, Collins FS, Boehnke M, Love MI, Koistinen HA, Laakso M, Mohlke KL, Small KS, and Scott LJ
Abstract: Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. Here, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34K conditionally distinct expression quantitative trait locus (eQTL) signals in 18K genes. Over half of eQTL genes exhibited at least two eQTL signals. Compared to primary signals, non-primary signals had lower effect sizes, lower minor allele frequencies, and less promoter enrichment; they corresponded to genes with higher heritability and higher tolerance for loss of function. Colocalization of eQTL with conditionally distinct genome-wide association study signals for 28 cardiometabolic traits identified 3,605 eQTL signals for 1,861 genes. Inclusion of non-primary eQTL signals increased colocalized signals by 46%. Among 30 genes with ≥2 pairs of colocalized signals, 21 showed a mediating gene dosage effect on the trait. Thus, expanded eQTL identification reveals more mechanisms underlying complex traits and improves understanding of the complexity of gene expression regulation., Competing Interests: Competing interests The authors declare no competing interests.
Published: 2023
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29. An integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D associated genes and regulatory signals.

Author: Zhao Z, D'Oliveira Albanus R, Taylor H, Tang X, Han Y, Orchard P, Varshney A, Zhang T, Manickam N, Erdos M, Narisu N, Taylor L, Saavedra X, Zhong A, Li B, Zhou T, Naji A, Liu C, Collins F, Parker SC, and Chen S
Abstract: Genome wide association studies (GWAS) have identified over 100 signals associated with type 1 diabetes (T1D). However, translating any given T1D GWAS signal into mechanistic insights, including putative causal variants and the context (cell type and cell state) in which they function, has been limited. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in healthy and autoantibody + (AAB+) human islets, as well as islets under multiple T1D stimulatory conditions. We broadly nominate effector cell types for all T1D GWAS signals. We further nominated higher-resolution contexts, including effector cell types, regulatory elements, and genes for three independent T1D risk variants acting through islet cells within the pancreas at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we created isogenic gene knockouts DLK1 -/- , RASGRP1 -/- , and TOX -/- , and the corresponding regulatory region knockout, RASGRP1 Δ , and DLK1 Δ hESCs. Loss of RASGRP1 or DLK1 , as well as knockout of the regulatory region of RASGRP1 or DLK1, increased β cell apoptosis. Additionally, pancreatic β cells derived from isogenic hESCs carrying the risk allele of rs3783355 A/A exhibited increased β cell death. Finally, RNA-seq and ATAC-seq identified five genes upregulated in both RASGRP1 -/- and DLK1 -/- β-like cells, four of which are associated with T1D. Together, this work reports an integrative approach for combining single cell multi-omics, GWAS, and isogenic hESC-derived β-like cells to prioritize the T1D associated signals and their underlying context-specific cell types, genes, SNPs, and regulatory elements, to illuminate biological functions and molecular mechanisms., Competing Interests: Conflict of Interest. S.C. is the co-founders of OncoBeat, LLC. and a consultant of Vesalius Therapeutics. The other authors declare no competing interest.
Published: 2023
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30. Bone dysplasia in Hutchinson-Gilford progeria syndrome is associated with dysregulated differentiation and function of bone cell populations.

Author: Cabral WA, Stephan C, Terajima M, Thaivalappil AA, Blanchard O, Tavarez UL, Narisu N, Yan T, Wincovitch SM, Taga Y, Yamauchi M, Kozloff KM, Erdos MR, and Collins FS
Subjects: Mice, Animals, Mutation, Lamin Type A genetics, Lamin Type A metabolism, Cell Differentiation, Progeria genetics, Progeria metabolism, Aging, Premature, Bone Diseases, Developmental
Abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder affecting tissues of mesenchymal origin. Most individuals with HGPS harbor a de novo c.1824C > T (p.G608G) mutation in the gene encoding lamin A (LMNA), which activates a cryptic splice donor site resulting in production of the toxic "progerin" protein. Clinical manifestations include growth deficiency, lipodystrophy, sclerotic dermis, cardiovascular defects, and bone dysplasia. Here we utilized the Lmna G609G knock-in (KI) mouse model of HGPS to further define mechanisms of bone loss associated with normal and premature aging disorders. Newborn skeletal staining of KI mice revealed altered rib cage shape and spinal curvature, and delayed calvarial mineralization with increased craniofacial and mandibular cartilage content. MicroCT analysis and mechanical testing of adult femurs indicated increased fragility associated with reduced bone mass, recapitulating the progressive bone deterioration that occurs in HGPS patients. We investigated mechanisms of bone loss in KI mice at the cellular level in bone cell populations. Formation of wild-type and KI osteoclasts from marrow-derived precursors was inhibited by KI osteoblast-conditioned media in vitro, suggesting a secreted factor(s) responsible for decreased osteoclasts on KI trabecular surfaces in vivo. Cultured KI osteoblasts exhibited abnormal differentiation characterized by reduced deposition and mineralization of extracellular matrix with increased lipid accumulation compared to wild-type, providing a mechanism for altered bone formation. Furthermore, quantitative analyses of KI transcripts confirmed upregulation of adipogenic genes both in vitro and in vivo. Thus, osteoblast phenotypic plasticity, inflammation and altered cellular cross-talk contribute to abnormal bone formation in HGPS mice., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
Published: 2023
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31. Modeling islet enhancers using deep learning identifies candidate causal variants at loci associated with T2D and glycemic traits.

Author: Hudaiberdiev S, Taylor DL, Song W, Narisu N, Bhuiyan RM, Taylor HJ, Tang X, Yan T, Swift AJ, Bonnycastle LL, Consortium D, Chen S, Stitzel ML, Erdos MR, Ovcharenko I, and Collins FS
Subjects: Genetic Variation, Humans, Computer Simulation, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 pathology, Deep Learning, Enhancer Elements, Genetic, Islets of Langerhans metabolism, Islets of Langerhans pathology
Abstract: Genetic association studies have identified hundreds of independent signals associated with type 2 diabetes (T2D) and related traits. Despite these successes, the identification of specific causal variants underlying a genetic association signal remains challenging. In this study, we describe a deep learning (DL) method to analyze the impact of sequence variants on enhancers. Focusing on pancreatic islets, a T2D relevant tissue, we show that our model learns islet-specific transcription factor (TF) regulatory patterns and can be used to prioritize candidate causal variants. At 101 genetic signals associated with T2D and related glycemic traits where multiple variants occur in linkage disequilibrium, our method nominates a single causal variant for each association signal, including three variants previously shown to alter reporter activity in islet-relevant cell types. For another signal associated with blood glucose levels, we biochemically test all candidate causal variants from statistical fine-mapping using a pancreatic islet beta cell line and show biochemical evidence of allelic effects on TF binding for the model-prioritized variant. To aid in future research, we publicly distribute our model and islet enhancer perturbation scores across ~67 million genetic variants. We anticipate that DL methods like the one presented in this study will enhance the prioritization of candidate causal variants for functional studies.
Published: 2023
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32. Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 hours.

Author: Grenko CM, Bonnycastle LL, Taylor HJ, Yan T, Swift AJ, Robertson CC, Narisu N, Erdos MR, Collins FS, and Taylor DL
Abstract: Disruption of pancreatic islet function and glucose homeostasis can lead to the development of sustained hyperglycemia, beta cell glucotoxicity, and ultimately type 2 diabetes (T2D). In this study, we sought to explore the effects of hyperglycemia on human pancreatic islet (HPI) gene expression by exposing HPIs from two donors to low (2.8mM) and high (15.0mM) glucose concentrations over 24 hours, assaying the transcriptome at seven time points using single-cell RNA sequencing (scRNA-seq). We modeled time as both a discrete and continuous variable to determine momentary and longitudinal changes in transcription associated with islet time in culture or glucose exposure. Across all cell types, we identified 1,528 genes associated with time, 1,185 genes associated with glucose exposure, and 845 genes associated with interaction effects between time and glucose. We clustered differentially expressed genes across cell types and found 347 modules of genes with similar expression patterns across time and glucose conditions, including two beta cell modules enriched in genes associated with T2D. Finally, by integrating genomic features from this study and genetic summary statistics for T2D and related traits, we nominate 363 candidate effector genes that may underlie genetic associations for T2D and related traits.
Published: 2023
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33. Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis.

Author: Tenney AP, Di Gioia SA, Webb BD, Chan WM, de Boer E, Garnai SJ, Barry BJ, Ray T, Kosicki M, Robson CD, Zhang Z, Collins TE, Gelber A, Pratt BM, Fujiwara Y, Varshney A, Lek M, Warburton PE, Van Ryzin C, Lehky TJ, Zalewski C, King KA, Brewer CC, Thurm A, Snow J, Facio FM, Narisu N, Bonnycastle LL, Swift A, Chines PS, Bell JL, Mohan S, Whitman MC, Staffieri SE, Elder JE, Demer JL, Torres A, Rachid E, Al-Haddad C, Boustany RM, Mackey DA, Brady AF, Fenollar-Cortés M, Fradin M, Kleefstra T, Padberg GW, Raskin S, Sato MT, Orkin SH, Parker SCJ, Hadlock TA, Vissers LELM, van Bokhoven H, Jabs EW, Collins FS, Pennacchio LA, Manoli I, and Engle EC
Subjects: Animals, Mice, GATA2 Transcription Factor genetics, GATA2 Transcription Factor metabolism, Motor Neurons metabolism, Neurogenesis, Neurons, Efferent, Facial Paralysis genetics, Facial Paralysis congenital, Facial Paralysis metabolism
Abstract: Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease., (© 2023. The Author(s).)
Published: 2023
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34. Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.

Author: Williamson A, Norris DM, Yin X, Broadaway KA, Moxley AH, Vadlamudi S, Wilson EP, Jackson AU, Ahuja V, Andersen MK, Arzumanyan Z, Bonnycastle LL, Bornstein SR, Bretschneider MP, Buchanan TA, Chang YC, Chuang LM, Chung RH, Clausen TD, Damm P, Delgado GE, de Mello VD, Dupuis J, Dwivedi OP, Erdos MR, Fernandes Silva L, Frayling TM, Gieger C, Goodarzi MO, Guo X, Gustafsson S, Hakaste L, Hammar U, Hatem G, Herrmann S, Højlund K, Horn K, Hsueh WA, Hung YJ, Hwu CM, Jonsson A, Kårhus LL, Kleber ME, Kovacs P, Lakka TA, Lauzon M, Lee IT, Lindgren CM, Lindström J, Linneberg A, Liu CT, Luan J, Aly DM, Mathiesen E, Moissl AP, Morris AP, Narisu N, Perakakis N, Peters A, Prasad RB, Rodionov RN, Roll K, Rundsten CF, Sarnowski C, Savonen K, Scholz M, Sharma S, Stinson SE, Suleman S, Tan J, Taylor KD, Uusitupa M, Vistisen D, Witte DR, Walther R, Wu P, Xiang AH, Zethelius B, Ahlqvist E, Bergman RN, Chen YI, Collins FS, Fall T, Florez JC, Fritsche A, Grallert H, Groop L, Hansen T, Koistinen HA, Komulainen P, Laakso M, Lind L, Loeffler M, März W, Meigs JB, Raffel LJ, Rauramaa R, Rotter JI, Schwarz PEH, Stumvoll M, Sundström J, Tönjes A, Tuomi T, Tuomilehto J, Wagner R, Barroso I, Walker M, Grarup N, Boehnke M, Wareham NJ, Mohlke KL, Wheeler E, O'Rahilly S, Fazakerley DJ, and Langenberg C
Subjects: Humans, Insulin genetics, Genome-Wide Association Study, Glucose metabolism, Blood Glucose genetics, Insulin Resistance genetics, Diabetes Mellitus, Type 2 genetics
Abstract: Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10 -8 ) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2023
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35. Functional interrogation of twenty type 2 diabetes-associated genes using isogenic hESC-derived β-like cells.

Author: Xue D, Narisu N, Taylor DL, Zhang M, Grenko C, Taylor HJ, Yan T, Tang X, Sinha N, Zhu J, Vandana JJ, Chong ACN, Lee A, Mansell EC, Swift AJ, Erdos MR, Zhou T, Bonnycastle LL, Zhong A, Chen S, and Collins FS
Abstract: Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional role of many loci has remained unexplored. In this study, we engineered isogenic knockout human embryonic stem cell (hESC) lines for 20 genes associated with T2D risk. We systematically examined β-cell differentiation, insulin production and secretion, and survival. We performed RNA-seq and ATAC-seq on hESC-β cells from each knockout line. Analyses of T2D GWAS signals overlapping with HNF4A-dependent ATAC peaks identified a specific SNP as a likely causal variant. In addition, we performed integrative association analyses and identified four genes ( CP, RNASE1, PCSK1N and GSTA2 ) associated with insulin production, and two genes ( TAGLN3 and DHRS2 ) associated with sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental hESC line, to identify a single likely functional variant at each of 23 T2D GWAS signals.
Published: 2023
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36. Human pancreatic islet microRNAs implicated in diabetes and related traits by large-scale genetic analysis.

Author: Taylor HJ, Hung YH, Narisu N, Erdos MR, Kanke M, Yan T, Grenko CM, Swift AJ, Bonnycastle LL, Sethupathy P, Collins FS, and Taylor DL
Subjects: Humans, Glycated Hemoglobin, Quantitative Trait Loci genetics, MicroRNAs metabolism, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Islets of Langerhans metabolism
Abstract: Genetic studies have identified ≥240 loci associated with the risk of type 2 diabetes (T2D), yet most of these loci lie in non-coding regions, masking the underlying molecular mechanisms. Recent studies investigating mRNA expression in human pancreatic islets have yielded important insights into the molecular drivers of normal islet function and T2D pathophysiology. However, similar studies investigating microRNA (miRNA) expression remain limited. Here, we present data from 63 individuals, the largest sequencing-based analysis of miRNA expression in human islets to date. We characterized the genetic regulation of miRNA expression by decomposing the expression of highly heritable miRNAs into cis- and trans- acting genetic components and mapping cis -acting loci associated with miRNA expression [miRNA-expression quantitative trait loci (eQTLs)]. We found i) 84 heritable miRNAs, primarily regulated by trans -acting genetic effects, and ii) 5 miRNA-eQTLs. We also used several different strategies to identify T2D-associated miRNAs. First, we colocalized miRNA-eQTLs with genetic loci associated with T2D and multiple glycemic traits, identifying one miRNA, miR-1908, that shares genetic signals for blood glucose and glycated hemoglobin (HbA1c). Next, we intersected miRNA seed regions and predicted target sites with credible set SNPs associated with T2D and glycemic traits and found 32 miRNAs that may have altered binding and function due to disrupted seed regions. Finally, we performed differential expression analysis and identified 14 miRNAs associated with T2D status-including miR-187-3p, miR-21-5p, miR-668, and miR-199b-5p-and 4 miRNAs associated with a polygenic score for HbA1c levels-miR-216a, miR-25, miR-30a-3p, and miR-30a-5p.
Published: 2023
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37. ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19.

Author: El-Sayed Moustafa JS, Jackson AU, Brotman SM, Guan L, Villicaña S, Roberts AL, Zito A, Bonnycastle L, Erdos MR, Narisu N, Stringham HM, Welch R, Yan T, Lakka T, Parker S, Tuomilehto J, Seow J, Graham C, Huettner I, Acors S, Kouphou N, Wadge S, Duncan EL, Steves CJ, Doores KJ, Malim MH, Collins FS, Pajukanta P, Boehnke M, Koistinen HA, Laakso M, Falchi M, Bell JT, Scott LJ, Mohlke KL, and Small KS
Subjects: Cardiometabolic Risk Factors, Diabetes Mellitus, Type 2 genetics, Endothelial Cells metabolism, Humans, Obesity, SARS-CoV-2, Adipose Tissue metabolism, Angiotensin-Converting Enzyme 2 genetics, Angiotensin-Converting Enzyme 2 metabolism, COVID-19 complications, COVID-19 genetics
Abstract: Background: COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain., Subjects/methods: In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), measured by RNA-Seq, which acts as a receptor for SARS-CoV-2 cellular entry., Results: Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) (P = 9.14 × 10 -6 ), obesity status (P = 4.81 × 10 -5 ), higher serum fasting insulin (P = 5.32 × 10 -4 ), BMI (P = 3.94 × 10 -4 ), and lower serum HDL levels (P = 1.92 × 10 -7 ). ACE2 expression was also associated with estimated proportions of cell types in adipose tissue: lower expression was associated with a lower proportion of microvascular endothelial cells (P = 4.25 × 10 -4 ) and higher proportion of macrophages (P = 2.74 × 10 -5 ). Despite an estimated heritability of 32%, we did not identify any proximal or distal expression quantitative trait loci (eQTLs) associated with adipose tissue ACE2 expression., Conclusions: Our results demonstrate that individuals with cardio-metabolic features known to increase risk of severe COVID-19 have lower background ACE2 levels in this highly relevant tissue. Reduced adipose tissue ACE2 expression may contribute to the pathophysiology of cardio-metabolic diseases, as well as the associated increased risk of severe COVID-19., (© 2022. The Author(s).)
Published: 2022
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38. SARS-CoV-2 infection induces beta cell transdifferentiation.

Author: Tang X, Uhl S, Zhang T, Xue D, Li B, Vandana JJ, Acklin JA, Bonnycastle LL, Narisu N, Erdos MR, Bram Y, Chandar V, Chong ACN, Lacko LA, Min Z, Lim JK, Borczuk AC, Xiang J, Naji A, Collins FS, Evans T, Liu C, tenOever BR, Schwartz RE, and Chen S
Subjects: Acetamides pharmacology, Adolescent, Adult, Aged, Aged, 80 and over, Animals, COVID-19 mortality, Chlorocebus aethiops, Cyclohexylamines pharmacology, Cytokines metabolism, Eukaryotic Initiation Factor-2 metabolism, Female, Glucagon, Host-Pathogen Interactions, Humans, Insulin metabolism, Insulin-Secreting Cells drug effects, Insulin-Secreting Cells metabolism, Insulin-Secreting Cells pathology, Male, Middle Aged, Phenotype, Signal Transduction, Tissue Culture Techniques, Trypsin metabolism, Vero Cells, Young Adult, COVID-19 virology, Cell Transdifferentiation drug effects, Insulin-Secreting Cells virology, SARS-CoV-2 pathogenicity
Abstract: Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from individuals with COVID-19. Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19., Competing Interests: Declaration of interests R.E.S. is on the scientific advisory board of Miromatrix Inc. and is a paid consultant and speaker for Alnylam Inc. The other authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2021
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39. Genetic effects on liver chromatin accessibility identify disease regulatory variants.

Author: Currin KW, Erdos MR, Narisu N, Rai V, Vadlamudi S, Perrin HJ, Idol JR, Yan T, Albanus RD, Broadaway KA, Etheridge AS, Bonnycastle LL, Orchard P, Didion JP, Chaudhry AS, Innocenti F, Schuetz EG, Scott LJ, Parker SCJ, Collins FS, and Mohlke KL
Subjects: Amino Acid Motifs, Binding Sites, Chromatin Assembly and Disassembly, Enhancer Elements, Genetic, Genetic Variation, Genome-Wide Association Study, Humans, Promoter Regions, Genetic, Protein Binding, Transcription Factors chemistry, Transcription Factors metabolism, Transcriptome, Chromatin metabolism, Liver metabolism, Quantitative Trait Loci
Abstract: Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTLs) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTLs have been identified in a limited set of human tissues. Here we mapped caQTLs in human liver tissue in 20 liver samples and identified 3,123 caQTLs. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTLs. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTLs and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTLs contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci., (Copyright © 2021 American Society of Human Genetics. All rights reserved.)
Published: 2021
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40. A Transcription Start Site Map in Human Pancreatic Islets Reveals Functional Regulatory Signatures.

Author: Varshney A, Kyono Y, Elangovan VR, Wang C, Erdos MR, Narisu N, Albanus RD, Orchard P, Stitzel ML, Collins FS, Kitzman JO, and Parker SCJ
Subjects: Enhancer Elements, Genetic, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Islets of Langerhans physiology, Transcription Initiation Site
Abstract: Identifying the tissue-specific molecular signatures of active regulatory elements is critical to understand gene regulatory mechanisms. Here, we identify transcription start sites (TSS) using cap analysis of gene expression (CAGE) across 57 human pancreatic islet samples. We identify 9,954 reproducible CAGE tag clusters (TCs), ∼20% of which are islet specific and occur mostly distal to known gene TSS. We integrated islet CAGE data with histone modification and chromatin accessibility profiles to identify epigenomic signatures of transcription initiation. Using a massively parallel reporter assay, we validated the transcriptional enhancer activity for 2,279 of 3,378 (∼68%) tested islet CAGE elements (5% false discovery rate). TCs within accessible enhancers show higher enrichment to overlap type 2 diabetes genome-wide association study (GWAS) signals than existing islet annotations, which emphasizes the utility of mapping CAGE profiles in disease-relevant tissue. This work provides a high-resolution map of transcriptional initiation in human pancreatic islets with utility for dissecting active enhancers at GWAS loci., (© 2021 by the American Diabetes Association.)
Published: 2021
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41. A targeted antisense therapeutic approach for Hutchinson-Gilford progeria syndrome.

Author: Erdos MR, Cabral WA, Tavarez UL, Cao K, Gvozdenovic-Jeremic J, Narisu N, Zerfas PM, Crumley S, Boku Y, Hanson G, Mourich DV, Kole R, Eckhaus MA, Gordon LB, and Collins FS
Subjects: Animals, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Morpholinos chemistry, Oligonucleotides, Antisense therapeutic use, Progeria drug therapy
Abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated aging disorder characterized by premature death from myocardial infarction or stroke. It is caused by de novo single-nucleotide mutations in the LMNA gene that activate a cryptic splice donor site, resulting in the production of a toxic form of lamin A, which is termed progerin. Here we present a potential genetic therapeutic strategy that utilizes antisense peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) to block pathogenic splicing of mutant transcripts. Of several candidates, PPMO SRP-2001 provided the most significant decrease in progerin transcripts in patient fibroblasts. Intravenous delivery of SRP-2001 to a transgenic mouse model of HGPS produced significant reduction of progerin transcripts in the aorta, a particularly critical target tissue in HGPS. Long-term continuous treatment with SRP-2001 yielded a 61.6% increase in lifespan and rescue of vascular smooth muscle cell loss in large arteries. These results provide a rationale for proceeding to human trials.
Published: 2021
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42. In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice.

Author: Koblan LW, Erdos MR, Wilson C, Cabral WA, Levy JM, Xiong ZM, Tavarez UL, Davison LM, Gete YG, Mao X, Newby GA, Doherty SP, Narisu N, Sheng Q, Krilow C, Lin CY, Gordon LB, Cao K, Collins FS, Brown JD, and Liu DR
Subjects: Alleles, Alternative Splicing, Animals, Aorta pathology, Base Pairing, Child, DNA genetics, Disease Models, Animal, Female, Fibroblasts metabolism, Humans, Lamin Type A chemistry, Lamin Type A genetics, Lamin Type A metabolism, Longevity, Male, Mice, Mice, Transgenic, Mutant Proteins chemistry, Mutant Proteins genetics, Mutant Proteins metabolism, Progeria pathology, RNA genetics, Adenine metabolism, Gene Editing methods, Mutation, Progeria genetics, Progeria therapy
Abstract: Hutchinson-Gilford progeria syndrome (HGPS or progeria) is typically caused by a dominant-negative C•G-to-T•A mutation (c.1824 C>T; p.G608G) in LMNA, the gene that encodes nuclear lamin A. This mutation causes RNA mis-splicing that produces progerin, a toxic protein that induces rapid ageing and shortens the lifespan of children with progeria to approximately 14 years 1-4 . Adenine base editors (ABEs) convert targeted A•T base pairs to G•C base pairs with minimal by-products and without requiring double-strand DNA breaks or donor DNA templates 5,6 . Here we describe the use of an ABE to directly correct the pathogenic HGPS mutation in cultured fibroblasts derived from children with progeria and in a mouse model of HGPS. Lentiviral delivery of the ABE to fibroblasts from children with HGPS resulted in 87-91% correction of the pathogenic allele, mitigation of RNA mis-splicing, reduced levels of progerin and correction of nuclear abnormalities. Unbiased off-target DNA and RNA editing analysis did not detect off-target editing in treated patient-derived fibroblasts. In transgenic mice that are homozygous for the human LMNA c.1824 C>T allele, a single retro-orbital injection of adeno-associated virus 9 (AAV9) encoding the ABE resulted in substantial, durable correction of the pathogenic mutation (around 20-60% across various organs six months after injection), restoration of normal RNA splicing and reduction of progerin protein levels. In vivo base editing rescued the vascular pathology of the mice, preserving vascular smooth muscle cell counts and preventing adventitial fibrosis. A single injection of ABE-expressing AAV9 at postnatal day 14 improved vitality and greatly extended the median lifespan of the mice from 215 to 510 days. These findings demonstrate the potential of in vivo base editing as a possible treatment for HGPS and other genetic diseases by directly correcting their root cause.
Published: 2021
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43. Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D.

Author: Viñuela A, Varshney A, van de Bunt M, Prasad RB, Asplund O, Bennett A, Boehnke M, Brown AA, Erdos MR, Fadista J, Hansson O, Hatem G, Howald C, Iyengar AK, Johnson P, Krus U, MacDonald PE, Mahajan A, Manning Fox JE, Narisu N, Nylander V, Orchard P, Oskolkov N, Panousis NI, Payne A, Stitzel ML, Vadlamudi S, Welch R, Collins FS, Mohlke KL, Gloyn AL, Scott LJ, Dermitzakis ET, Groop L, Parker SCJ, and McCarthy MI
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Animals, Blood Glucose metabolism, Cell Line, Tumor, Cohort Studies, Diabetes Mellitus, Type 2 blood, Diacylglycerol Kinase genetics, Diacylglycerol Kinase metabolism, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Genome-Wide Association Study, Humans, Male, Mice, Middle Aged, Polymorphism, Single Nucleotide, RNA-Seq, Sequence Analysis, DNA, Transcription Factor 7-Like 2 Protein genetics, Transcription Factor 7-Like 2 Protein metabolism, Young Adult, Blood Glucose genetics, Diabetes Mellitus, Type 2 genetics, Genetic Predisposition to Disease, Islets of Langerhans metabolism, Quantitative Trait Loci
Abstract: Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues.
Published: 2020
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44. Adiponectin GWAS loci harboring extensive allelic heterogeneity exhibit distinct molecular consequences.

Author: Spracklen CN, Iyengar AK, Vadlamudi S, Raulerson CK, Jackson AU, Brotman SM, Wu Y, Cannon ME, Davis JP, Crain AT, Currin KW, Perrin HJ, Narisu N, Stringham HM, Fuchsberger C, Locke AE, Welch RP, Kuusisto JK, Pajukanta P, Scott LJ, Li Y, Collins FS, Boehnke M, Laakso M, and Mohlke KL
Subjects: Alleles, Cadherins genetics, Cadherins metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Gene Frequency genetics, Genetic Predisposition to Disease, Genome-Wide Association Study methods, Humans, Insulin Receptor Substrate Proteins genetics, Insulin Receptor Substrate Proteins metabolism, Male, Metabolic Syndrome genetics, Phenotype, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci genetics, Regulatory Sequences, Nucleic Acid, Transcription Factors genetics, Transcription Factors metabolism, Adiponectin genetics, Adiponectin metabolism, Adipose Tissue metabolism
Abstract: Loci identified in genome-wide association studies (GWAS) can include multiple distinct association signals. We sought to identify the molecular basis of multiple association signals for adiponectin, a hormone involved in glucose regulation secreted almost exclusively from adipose tissue, identified in the Metabolic Syndrome in Men (METSIM) study. With GWAS data for 9,262 men, four loci were significantly associated with adiponectin: ADIPOQ, CDH13, IRS1, and PBRM1. We performed stepwise conditional analyses to identify distinct association signals, a subset of which are also nearly independent (lead variant pairwise r2<0.01). Two loci exhibited allelic heterogeneity, ADIPOQ and CDH13. Of seven association signals at the ADIPOQ locus, two signals colocalized with adipose tissue expression quantitative trait loci (eQTLs) for three transcripts: trait-increasing alleles at one signal were associated with increased ADIPOQ and LINC02043, while trait-increasing alleles at the other signal were associated with decreased ADIPOQ-AS1. In reporter assays, adiponectin-increasing alleles at two signals showed corresponding directions of effect on transcriptional activity. Putative mechanisms for the seven ADIPOQ signals include a missense variant (ADIPOQ G90S), a splice variant, a promoter variant, and four enhancer variants. Of two association signals at the CDH13 locus, the first signal consisted of promoter variants, including the lead adipose tissue eQTL variant for CDH13, while a second signal included a distal intron 1 enhancer variant that showed ~2-fold allelic differences in transcriptional reporter activity. Fine-mapping and experimental validation demonstrated that multiple, distinct association signals at these loci can influence multiple transcripts through multiple molecular mechanisms., Competing Interests: The authors have declared that no competing interests exist.
Published: 2020
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45. ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition.

Author: El-Sayed Moustafa JS, Jackson AU, Brotman SM, Guan L, Villicaña S, Roberts AL, Zito A, Bonnycastle L, Erdos MR, Narisu N, Stringham HM, Welch R, Yan T, Lakka T, Parker S, Tuomilehto J, Collins FS, Pajukanta P, Boehnke M, Koistinen HA, Laakso M, Falchi M, Bell JT, Scott LJ, Mohlke KL, and Small KS
Abstract: COVID-19 severity has varied widely, with demographic and cardio-metabolic factors increasing risk of severe reactions to SARS-CoV-2 infection, but the underlying mechanisms for this remain uncertain. We investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 ( ACE2 ), which has been shown to act as a receptor for SARS-CoV-2 cellular entry. In a meta-analysis of three independent studies including up to 1,471 participants, lower adipose tissue ACE2 expression was associated with adverse cardio-metabolic health indices including type 2 diabetes (T2D) and obesity status, higher serum fasting insulin and BMI, and lower serum HDL levels (P<5.32x10 -4 ). ACE2 expression levels were also associated with estimated proportions of cell types in adipose tissue; lower ACE2 expression was associated with a lower proportion of microvascular endothelial cells (P=4.25x10 -4 ) and higher macrophage proportion (P=2.74x10 -5 ), suggesting a link to inflammation. Despite an estimated heritability of 32%, we did not identify any proximal or distal genetic variants (eQTLs) associated with adipose tissue ACE2 expression. Our results demonstrate that at-risk individuals have lower background ACE2 levels in this highly relevant tissue. Further studies will be required to establish how this may contribute to increased COVID-19 severity.
Published: 2020
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46. Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures.

Author: Rai V, Quang DX, Erdos MR, Cusanovich DA, Daza RM, Narisu N, Zou LS, Didion JP, Guan Y, Shendure J, Parker SCJ, and Collins FS
Subjects: Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 pathology, Gene Expression Profiling, Humans, Islets of Langerhans metabolism, Polymorphism, Single Nucleotide genetics, Chromatin Immunoprecipitation Sequencing, Deep Learning, Diabetes Mellitus, Type 2 genetics, Islets of Langerhans pathology, Single-Cell Analysis
Abstract: Objective: Type 2 diabetes (T2D) is a complex disease characterized by pancreatic islet dysfunction, insulin resistance, and disruption of blood glucose levels. Genome-wide association studies (GWAS) have identified > 400 independent signals that encode genetic predisposition. More than 90% of associated single-nucleotide polymorphisms (SNPs) localize to non-coding regions and are enriched in chromatin-defined islet enhancer elements, indicating a strong transcriptional regulatory component to disease susceptibility. Pancreatic islets are a mixture of cell types that express distinct hormonal programs, so each cell type may contribute differentially to the underlying regulatory processes that modulate T2D-associated transcriptional circuits. Existing chromatin profiling methods such as ATAC-seq and DNase-seq, applied to islets in bulk, produce aggregate profiles that mask important cellular and regulatory heterogeneity., Methods: We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq). We also developed a deep learning model based on U-Net architecture to accurately predict open chromatin peak calls in rare cell populations., Results: We show that sci-ATAC-seq profiles allow us to deconvolve alpha, beta, and delta cell populations and identify cell-type-specific regulatory signatures underlying T2D. Particularly, T2D GWAS SNPs are significantly enriched in beta cell-specific and across cell-type shared islet open chromatin, but not in alpha or delta cell-specific open chromatin. We also demonstrate, using less abundant delta cells, that deep learning models can improve signal recovery and feature reconstruction of rarer cell populations. Finally, we use co-accessibility measures to nominate the cell-specific target genes at 104 non-coding T2D GWAS signals., Conclusions: Collectively, we identify the islet cell type of action across genetic signals of T2D predisposition and provide higher-resolution mechanistic insights into genetically encoded risk pathways., (Published by Elsevier GmbH.)
Published: 2020
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47. Single-cell transcriptomics from human pancreatic islets: sample preparation matters.

Author: Bonnycastle LL, Gildea DE, Yan T, Narisu N, Swift AJ, Wolfsberg TG, Erdos MR, and Collins FS
Abstract: Single-cell RNA sequencing (scRNA-seq) of human primary tissues is a rapidly emerging tool for investigating human health and disease at the molecular level. However, optimal processing of solid tissues presents a number of technical and logistical challenges, especially for tissues that are only available at autopsy, which includes pancreatic islets, a tissue that is highly relevant to diabetes. To assess the possible effects of different sample preparation protocols on fresh islet samples, we performed a detailed comparison of scRNA-seq data generated with islets isolated from a human donor but processed according to four treatment strategies, including fixation and cryopreservation. We found significant and reproducible differences in the proportion of cell types identified, and more minor effects on cell-specific patterns of gene expression. Fresh islets from a second donor confirmed gene expression signatures of alpha and beta subclusters. These findings may well apply to other tissues, emphasizing the need for careful consideration when choosing processing methods, comparing results between different studies, and/or interpreting data in the context of multiple cell types from preserved tissue., (Published by Oxford University Press 2019. This work is written by US Government employees and is in the public domain in the US.)
Published: 2020
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48. Colocalization of GWAS and eQTL signals at loci with multiple signals identifies additional candidate genes for body fat distribution.

Author: Wu Y, Broadaway KA, Raulerson CK, Scott LJ, Pan C, Ko A, He A, Tilford C, Fuchsberger C, Locke AE, Stringham HM, Jackson AU, Narisu N, Kuusisto J, Pajukanta P, Collins FS, Boehnke M, Laakso M, Lusis AJ, Civelek M, and Mohlke KL
Subjects: Adult, Bayes Theorem, Body Mass Index, Female, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, Male, Phenotype, Polymorphism, Single Nucleotide, Subcutaneous Fat metabolism, Waist-Hip Ratio methods, Adipose Tissue physiology, Body Fat Distribution, Genome-Wide Association Study methods, Metabolic Syndrome genetics, Quantitative Trait Loci
Abstract: Integration of genome-wide association study (GWAS) signals with expression quantitative trait loci (eQTL) studies enables identification of candidate genes. However, evaluating whether nearby signals may share causal variants, termed colocalization, is affected by the presence of allelic heterogeneity, different variants at the same locus impacting the same phenotype. We previously identified eQTL in subcutaneous adipose tissue from 770 participants in the Metabolic Syndrome in Men (METSIM) study and detected 15 eQTL signals that colocalized with GWAS signals for waist-hip ratio adjusted for body mass index (WHRadjBMI) from the Genetic Investigation of Anthropometric Traits consortium. Here, we reevaluated evidence of colocalization using two approaches, conditional analysis and the Bayesian test COLOC, and show that providing COLOC with approximate conditional summary statistics at multi-signal GWAS loci can reconcile disagreements in colocalization classification between the two tests. Next, we performed conditional analysis on the METSIM subcutaneous adipose tissue data to identify conditionally distinct or secondary eQTL signals. We used the two approaches to test for colocalization with WHRadjBMI GWAS signals and evaluated the differences in colocalization classification between the two tests. Through these analyses, we identified four GWAS signals colocalized with secondary eQTL signals for FAM13A, SSR3, GRB14 and FMO1. Thus, at loci with multiple eQTL and/or GWAS signals, analyzing each signal independently enabled additional candidate genes to be identified., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Published: 2019
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49. Analysis of somatic mutations identifies signs of selection during in vitro aging of primary dermal fibroblasts.

Author: Narisu N, Rothwell R, Vrtačnik P, Rodríguez S, Didion J, Zöllner S, Erdos MR, Collins FS, and Eriksson M
Subjects: Adolescent, Aged, 80 and over, Cells, Cultured, Child, Child, Preschool, DNA genetics, Female, Fibroblasts metabolism, Humans, Male, Sequence Analysis, RNA, Skin metabolism, Cellular Senescence genetics, Fibroblasts cytology, Mutation, Skin cytology
Abstract: Somatic mutations are critical for cancer development and may play a role in age-related functional decline. Here, we used deep sequencing to analyze the prevalence of somatic mutations during in vitro cell aging. Primary dermal fibroblasts from healthy subjects of young and advanced age, from Hutchinson-Gilford progeria syndrome and from xeroderma pigmentosum complementation groups A and C, were first restricted in number and then expanded in vitro. DNA was obtained from cells pre- and post-expansion and sequenced at high depth (1656× mean coverage), over a cumulative 290 kb target region, including the exons of 44 aging-related genes. Allele frequencies of 58 somatic mutations differed between the pre- and post-cell culture expansion passages. Mathematical modeling revealed that the frequency change of three of the 58 mutations was unlikely to be explained by genetic drift alone, indicative of positive selection. Two of these three mutations, CDKN2A c.53C>T (T18M) and ERCC8 c.*772T>A, were identified in cells from a patient with XPA. The allele frequency of the CDKN2A mutation increased from 0% to 55.3% with increasing cell culture passage. The third mutation, BRCA2 c.6222C>T (H2074H), was identified in a sample from a healthy individual of advanced age. However, further validation of the three mutations suggests that other unmeasured variants probably provide the selective advantage in these cells. Our results reinforce the notions that somatic mutations occur during aging and that some are under positive selection, supporting the model of increased tissue heterogeneity with increased age., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Published: 2019
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50. Adipose Tissue Gene Expression Associations Reveal Hundreds of Candidate Genes for Cardiometabolic Traits.

Author: Raulerson CK, Ko A, Kidd JC, Currin KW, Brotman SM, Cannon ME, Wu Y, Spracklen CN, Jackson AU, Stringham HM, Welch RP, Fuchsberger C, Locke AE, Narisu N, Lusis AJ, Civelek M, Furey TS, Kuusisto J, Collins FS, Boehnke M, Scott LJ, Lin DY, Love MI, Laakso M, Pajukanta P, and Mohlke KL
Subjects: Alleles, Body Mass Index, Finland, Genome-Wide Association Study, Humans, Male, Quantitative Trait Loci, Waist-Hip Ratio, Adipose Tissue metabolism, Diabetes Mellitus, Type 2 genetics, Gene Expression, Obesity genetics
Abstract: Genome-wide association studies (GWASs) have identified thousands of genetic loci associated with cardiometabolic traits including type 2 diabetes (T2D), lipid levels, body fat distribution, and adiposity, although most causal genes remain unknown. We used subcutaneous adipose tissue RNA-seq data from 434 Finnish men from the METSIM study to identify 9,687 primary and 2,785 secondary cis-expression quantitative trait loci (eQTL; <1 Mb from TSS, FDR < 1%). Compared to primary eQTL signals, secondary eQTL signals were located further from transcription start sites, had smaller effect sizes, and were less enriched in adipose tissue regulatory elements compared to primary signals. Among 2,843 cardiometabolic GWAS signals, 262 colocalized by LD and conditional analysis with 318 transcripts as primary and conditionally distinct secondary cis-eQTLs, including some across ancestries. Of cardiometabolic traits examined for adipose tissue eQTL colocalizations, waist-hip ratio (WHR) and circulating lipid traits had the highest percentage of colocalized eQTLs (15% and 14%, respectively). Among alleles associated with increased cardiometabolic GWAS risk, approximately half (53%) were associated with decreased gene expression level. Mediation analyses of colocalized genes and cardiometabolic traits within the 434 individuals provided further evidence that gene expression influences variant-trait associations. These results identify hundreds of candidate genes that may act in adipose tissue to influence cardiometabolic traits., (Copyright © 2019 American Society of Human Genetics. All rights reserved.)
Published: 2019
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