New genetic loci link adipose and insulin biology to body fat distribution


Autoria(s): Shungin, Dmitry; Winkler, Thomas W; Croteau-Chonka, Damien C; Ferreira, Teresa; Locke, Adam E; Mägi, Reedik; Strawbridge, Rona J; Pers, Tune H; Fischer, Krista; Justice, Anne E; Workalemahu, Tsegaselassie; Wu, Joseph M W; Buchkovich, Martin L; Heard-Costa, Nancy L; Roman, Tamara S; Drong, Alexander W; Song, Ci; Gustafsson, Stefan; Day, Felix R; Esko, Tonu; Fall, Tove; Kutalik, Zoltán; Luan, Jian'an; Randall, Joshua C; Scherag, André; Vedantam, Sailaja; Wood, Andrew R; Chen, Jin; Fehrmann, Rudolf; Karjalainen, Juha; Kahali, Bratati; Liu, Ching-Ti; Schmidt, Ellen M; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bragg-Gresham, Jennifer L; Buyske, Steven; Demirkan, Ayse; Ehret, Georg B; Feitosa, Mary F; Goel, Anuj; Jackson, Anne U; Johnson, Toby; Kleber, Marcus E; Kristiansson, Kati; Mangino, Massimo; Mateo Leach, Irene; Medina-Gomez, Carolina; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Peters, Marjolein J; Prokopenko, Inga; Stančáková, Alena; Ju Sung, Yun; Tanaka, Toshiko; Teumer, Alexander; Van Vliet-Ostaptchouk, Jana V; Yengo, Loïc; Zhang, Weihua; Albrecht, Eva; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Böhringer, Stefan; Bonnet, Fabrice; Böttcher, Yvonne; Bruinenberg, Marcel; Carba, Delia B; Caspersen, Ida H; Clarke, Robert; Daw, E Warwick; Deelen, Joris; Deelman, Ewa; Delgado, Graciela; Doney, Alex S F; Eklund, Niina; Erdos, Michael R; Estrada, Karol; Eury, Elodie; Friedrich, Nele; Garcia, Melissa E; Giedraitis, Vilmantas; Gigante, Bruna; Go, Alan S; Golay, Alain; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grewal, Jagvir; Groves, Christopher J; Haller, Toomas; Hallmans, Goran; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heikkilä, Kauko; Herzig, Karl-Heinz; Helmer, Quinta; Hillege, Hans L; Holmen, Oddgeir; Hunt, Steven C; Isaacs, Aaron; Ittermann, Till; James, Alan L; Johansson, Ingegerd; Juliusdottir, Thorhildur; Kalafati, Ioanna-Panagiota; Kinnunen, Leena; Koenig, Wolfgang; Kooner, Ishminder K; Kratzer, Wolfgang; Lamina, Claudia; Leander, Karin; Lee, Nanette R; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Mach, François; Magnusson, Patrik K E; Mahajan, Anubha; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Moayyeri, Alireza; Monda, Keri L; Mooijaart, Simon P; Mühleisen, Thomas W; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nalls, Michael A; Narisu, Narisu; Glorioso, Nicola; Nolte, Ilja M; Olden, Matthias; Rayner, Nigel W; Renstrom, Frida; Ried, Janina S; Robertson, Neil R; Rose, Lynda M; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Sennblad, Bengt; Seufferlein, Thomas; Sitlani, Colleen M; Vernon Smith, Albert; Stirrups, Kathleen; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorand, Barbara; Thorleifsson, Gudmar; Tomaschitz, Andreas; Troffa, Chiara; van Oort, Floor V A; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Wennauer, Roman; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Zhang, Qunyuan; Hua Zhao, Jing; Brennan, Eoin P; Choi, Murim; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Gharavi, Ali G; Hedman, Åsa K; Hivert, Marie-France; Huang, Jinyan; Kanoni, Stavroula; Karpe, Fredrik; Keildson, Sarah; Kiryluk, Krzysztof; Liang, Liming; Lifton, Richard P; Ma, Baoshan; McKnight, Amy J; McPherson, Ruth; Metspalu, Andres; Min, Josine L; Moffatt, Miriam F; Montgomery, Grant W; Murabito, Joanne M; Nicholson, George; Nyholt, Dale R; Olsson, Christian; Perry, John R B; Reinmaa, Eva; Salem, Rany M; Sandholm, Niina; Schadt, Eric E; Scott, Robert A; Stolk, Lisette; Vallejo, Edgar E; Westra, Harm-Jan; Zondervan, Krina T; Amouyel, Philippe; Arveiler, Dominique; Bakker, Stephan J L; Beilby, John; Bergman, Richard N; Blangero, John; Brown, Morris J; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chines, Peter S; Claudi-Boehm, Simone; Collins, Francis S; Crawford, Dana C; Danesh, John; de Faire, Ulf; de Geus, Eco J C; Dörr, Marcus; Erbel, Raimund; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Forouhi, Nita G; Forrester, Terrence; Franco, Oscar H; Gansevoort, Ron T; Gieger, Christian; Gudnason, Vilmundur; Haiman, Christopher A; Harris, Tamara B; Hattersley, Andrew T; Heliövaara, Markku; Hicks, Andrew A; Hingorani, Aroon D; Hoffmann, Wolfgang; Hofman, Albert; Homuth, Georg; Humphries, Steve E; Hyppönen, Elina; Illig, Thomas; Jarvelin, Marjo-Riitta; Johansen, Berit; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kooner, Jaspal S; Kooperberg, Charles; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lyssenko, Valeriya; Männistö, Satu; Marette, André; Matise, Tara C; McKenzie, Colin A; McKnight, Barbara; Musk, Arthur W; Möhlenkamp, Stefan; Morris, Andrew D; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Palmer, Lyle J; Penninx, Brenda W; Peters, Annette; Pramstaller, Peter P; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Ridker, Paul M; Ritchie, Marylyn D; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter E H; Shuldiner, Alan R; Staessen, Jan A; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Strauch, Konstantin; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Vohl, Marie-Claude; Völker, Uwe; Vollenweider, Peter; Wilson, James F; Witteman, Jacqueline C; Adair, Linda S; Bochud, Murielle; Boehm, Bernhard O; Bornstein, Stefan R; Bouchard, Claude; Cauchi, Stéphane; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Cooper, Richard S; Dedoussis, George; Ferrucci, Luigi; Froguel, Philippe; Grabe, Hans-Jörgen; Hamsten, Anders; Hui, Jennie; Hveem, Kristian; Jöckel, Karl-Heinz; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; März, Winfried; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin N A; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Rivadeneira, Fernando; Saaristo, Timo E; Saleheen, Danish; Sinisalo, Juha; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; van der Harst, Pim; Veronesi, Giovanni; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Abecasis, Goncalo R; Assimes, Themistocles L; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; Franke, Lude; Frayling, Timothy M; Groop, Leif C; Hunter, David J; Kaplan, Robert C; O'Connell, Jeffrey R; Qi, Lu; Schlessinger, David; Strachan, David P; Stefansson, Kari; van Duijn, Cornelia M; Willer, Cristen J; Visscher, Peter M; Yang, Jian; Hirschhorn, Joel N; Zillikens, M Carola; McCarthy, Mark I; Speliotes, Elizabeth K; North, Kari E; Fox, Caroline S; Barroso, Inês; Franks, Paul W; Ingelsson, Erik; Heid, Iris M; Loos, Ruth J F; Cupples, L Adrienne; Morris, Andrew P; Lindgren, Cecilia M; Mohlke, Karen L; ADIPOGen Consortium
Data(s)

12/02/2015

Resumo

<p>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.</p>

Identificador

http://pure.qub.ac.uk/portal/en/publications/new-genetic-loci-link-adipose-and-insulin-biology-to-body-fat-distribution(f6a5405e-39dd-473d-b002-31cace4e52c5).html

http://dx.doi.org/10.1038/nature14132

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Shungin , D , Winkler , T W , Croteau-Chonka , D C , Ferreira , T , Locke , A E , Mägi , R , Strawbridge , R J , Pers , T H , Fischer , K , Justice , A E , Workalemahu , T , Wu , J M W , Buchkovich , M L , Heard-Costa , N L , Roman , T S , Drong , A W , Song , C , Gustafsson , S , Day , F R , Esko , T , Fall , T , Kutalik , Z , Luan , J , Randall , J C , Scherag , A , Vedantam , S , Wood , A R , Chen , J , Fehrmann , R , Karjalainen , J , Kahali , B , Liu , C-T , Schmidt , E M , Absher , D , Amin , N , Anderson , D , Beekman , M , Bragg-Gresham , J L , Buyske , S , Demirkan , A , Ehret , G B , Feitosa , M F , Goel , A , Jackson , A U , Johnson , T , Kleber , M E , Kristiansson , K , Mangino , M , Mateo Leach , I , Medina-Gomez , C , Palmer , C D , Pasko , D , Pechlivanis , S , Peters , M J , Prokopenko , I , Stančáková , A , Ju Sung , Y , Tanaka , T , Teumer , A , Van Vliet-Ostaptchouk , J V , Yengo , L , Zhang , W , Albrecht , E , Ärnlöv , J , Arscott , G M , Bandinelli , S , Barrett , A , Bellis , C , Bennett , A J , Berne , C , Blüher , M , Böhringer , S , Bonnet , F , Böttcher , Y , Bruinenberg , M , Carba , D B , Caspersen , I H , Clarke , R , Daw , E W , Deelen , J , Deelman , E , Delgado , G , Doney , A S F , Eklund , N , Erdos , M R , Estrada , K , Eury , E , Friedrich , N , Garcia , M E , Giedraitis , V , Gigante , B , Go , A S , Golay , A , Grallert , H , Grammer , T B , Gräßler , J , Grewal , J , Groves , C J , Haller , T , Hallmans , G , Hartman , C A , Hassinen , M , Hayward , C , Heikkilä , K , Herzig , K-H , Helmer , Q , Hillege , H L , Holmen , O , Hunt , S C , Isaacs , A , Ittermann , T , James , A L , Johansson , I , Juliusdottir , T , Kalafati , I-P , Kinnunen , L , Koenig , W , Kooner , I K , Kratzer , W , Lamina , C , Leander , K , Lee , N R , Lichtner , P , Lind , L , Lindström , J , Lobbens , S , Lorentzon , M , Mach , F , Magnusson , P K E , Mahajan , A , McArdle , W L , Menni , C , Merger , S , Mihailov , E , Milani , L , Mills , R , Moayyeri , A , Monda , K L , Mooijaart , S P , Mühleisen , T W , Mulas , A , Müller , G , Müller-Nurasyid , M , Nagaraja , R , Nalls , M A , Narisu , N , Glorioso , N , Nolte , I M , Olden , M , Rayner , N W , Renstrom , F , Ried , J S , Robertson , N R , Rose , L M , Sanna , S , Scharnagl , H , Scholtens , S , Sennblad , B , Seufferlein , T , Sitlani , C M , Vernon Smith , A , Stirrups , K , Stringham , H M , Sundström , J , Swertz , M A , Swift , A J , Syvänen , A-C , Tayo , B O , Thorand , B , Thorleifsson , G , Tomaschitz , A , Troffa , C , van Oort , F V A , Verweij , N , Vonk , J M , Waite , L L , Wennauer , R , Wilsgaard , T , Wojczynski , M K , Wong , A , Zhang , Q , Hua Zhao , J , Brennan , E P , Choi , M , Eriksson , P , Folkersen , L , Franco-Cereceda , A , Gharavi , A G , Hedman , Å K , Hivert , M-F , Huang , J , Kanoni , S , Karpe , F , Keildson , S , Kiryluk , K , Liang , L , Lifton , R P , Ma , B , McKnight , A J , McPherson , R , Metspalu , A , Min , J L , Moffatt , M F , Montgomery , G W , Murabito , J M , Nicholson , G , Nyholt , D R , Olsson , C , Perry , J R B , Reinmaa , E , Salem , R M , Sandholm , N , Schadt , E E , Scott , R A , Stolk , L , Vallejo , E E , Westra , H-J , Zondervan , K T , Amouyel , P , Arveiler , D , Bakker , S J L , Beilby , J , Bergman , R N , Blangero , J , Brown , M J , Burnier , M , Campbell , H , Chakravarti , A , Chines , P S , Claudi-Boehm , S , Collins , F S , Crawford , D C , Danesh , J , de Faire , U , de Geus , E J C , Dörr , M , Erbel , R , Eriksson , J G , Farrall , M , Ferrannini , E , Ferrières , J , Forouhi , N G , Forrester , T , Franco , O H , Gansevoort , R T , Gieger , C , Gudnason , V , Haiman , C A , Harris , T B , Hattersley , A T , Heliövaara , M , Hicks , A A , Hingorani , A D , Hoffmann , W , Hofman , A , Homuth , G , Humphries , S E , Hyppönen , E , Illig , T , Jarvelin , M-R , Johansen , B , Jousilahti , P , Jula , A M , Kaprio , J , Kee , F , Keinanen-Kiukaanniemi , S M , Kooner , J S , Kooperberg , C , Kovacs , P , Kraja , A T , Kumari , M , Kuulasmaa , K , Kuusisto , J , Lakka , T A , Langenberg , C , Le Marchand , L , Lehtimäki , T , Lyssenko , V , Männistö , S , Marette , A , Matise , T C , McKenzie , C A , McKnight , B , Musk , A W , Möhlenkamp , S , Morris , A D , Nelis , M , Ohlsson , C , Oldehinkel , A J , Ong , K K , Palmer , L J , Penninx , B W , Peters , A , Pramstaller , P P , Raitakari , O T , Rankinen , T , Rao , D C , Rice , T K , Ridker , P M , Ritchie , M D , Rudan , I , Salomaa , V , Samani , N J , Saramies , J , Sarzynski , M A , Schwarz , P E H , Shuldiner , A R , Staessen , J A , Steinthorsdottir , V , Stolk , R P , Strauch , K , Tönjes , A , Tremblay , A , Tremoli , E , Vohl , M-C , Völker , U , Vollenweider , P , Wilson , J F , Witteman , J C , Adair , L S , Bochud , M , Boehm , B O , Bornstein , S R , Bouchard , C , Cauchi , S , Caulfield , M J , Chambers , J C , Chasman , D I , Cooper , R S , Dedoussis , G , Ferrucci , L , Froguel , P , Grabe , H-J , Hamsten , A , Hui , J , Hveem , K , Jöckel , K-H , Kivimaki , M , Kuh , D , Laakso , M , Liu , Y , März , W , Munroe , P B , Njølstad , I , Oostra , B A , Palmer , C N A , Pedersen , N L , Perola , M , Pérusse , L , Peters , U , Power , C , Quertermous , T , Rauramaa , R , Rivadeneira , F , Saaristo , T E , Saleheen , D , Sinisalo , J , Slagboom , P E , Snieder , H , Spector , T D , Thorsteinsdottir , U , Stumvoll , M , Tuomilehto , J , Uitterlinden , A G , Uusitupa , M , van der Harst , P , Veronesi , G , Walker , M , Wareham , N J , Watkins , H , Wichmann , H-E , Abecasis , G R , Assimes , T L , Berndt , S I , Boehnke , M , Borecki , I B , Deloukas , P , Franke , L , Frayling , T M , Groop , L C , Hunter , D J , Kaplan , R C , O'Connell , J R , Qi , L , Schlessinger , D , Strachan , D P , Stefansson , K , van Duijn , C M , Willer , C J , Visscher , P M , Yang , J , Hirschhorn , J N , Zillikens , M C , McCarthy , M I , Speliotes , E K , North , K E , Fox , C S , Barroso , I , Franks , P W , Ingelsson , E , Heid , I M , Loos , R J F , Cupples , L A , Morris , A P , Lindgren , C M , Mohlke , K L & ADIPOGen Consortium 2015 , ' New genetic loci link adipose and insulin biology to body fat distribution ' Nature , vol 518 , no. 7538 , pp. 187-196 . DOI: 10.1038/nature14132

Tipo

article