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

Publication

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

Journal Paper/Review - Feb 12, 2015

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

Citation

Hofman A, Kovacs P, Kraja A, Kumari M, Kuulasmaa K, Kuusisto J, Lakka T, Langenberg C, Le Marchand L, Lehtimäki T, Lyssenko V, Kooperberg C, Kooner J, Keinanen-Kiukaanniemi S, Homuth G, Humphries S, Hyppönen E, Illig T, Jarvelin M, Johansen B, Jousilahti P, Jula A, Kaprio J, Kee F, Männistö S, Marette A, Pramstaller P, Raitakari O, Rankinen T, Rao D, Rice T, Ridker P, Ritchie M, Rudan I, Salomaa V, Samani N, Peters A, Penninx B, Palmer L, Matise T, McKenzie C, McKnight B, Musk A, Möhlenkamp S, Morris A, Nelis M, Ohlsson C, Oldehinkel A, Ong K, Saramies J, Hoffmann W, Murabito J, Amouyel P, Arveiler D, Bakker S, Beilby J, Bergman R, Blangero J, Brown M, Burnier M, Campbell H, Zondervan K, Westra H, Vallejo E, Nicholson G, Nyholt D, Olsson C, Perry J, Reinmaa E, Salem R, Sandholm N, Schadt E, Scott R, Stolk L, Chakravarti A, Chines P, Forrester T, Franco O, Gansevoort R, Gieger C, Gudnason V, Haiman C, Harris T, Hattersley A, Heliövaara M, Hicks A, Forouhi N, Ferrieres J, Ferrannini E, Claudi-Boehm S, Collins F, Crawford D, Danesh J, de Faire U, de Geus E, Dörr M, Erbel R, Eriksson J, Farrall M, Hingorani A, Sarzynski M, Sinisalo J, Wichmann H, Abecasis G, Assimes T, Berndt S, Boehnke M, Borecki I, Deloukas P, Franke L, Frayling T, Groop L, Watkins H, Wareham N, Walker M, Slagboom P, Snieder H, Spector T, Stefansson K, Stumvoll M, Tuomilehto J, Uitterlinden A, Uusitupa M, van der Harst P, Veronesi G, Hunter D, Kaplan R, North K, Fox C, Barroso I, Franks P, Ingelsson E, Heid I, Loos R, Cupples L, Morris A, Lindgren C, Speliotes E, McCarthy M, Zillikens M, O'Connell J, Qi L, Schlessinger D, Strachan D, Thorsteinsdottir U, van Duijn C, Willer C, Visscher P, Yang J, Hirschhorn J, Mohlke K, Saleheen D, Schwarz P, Adair L, Bochud M, Boehm B, Bornstein S, Bouchard C, Cauchi S, Caulfield M, Chambers J, Chasman D, Cooper R, Witteman J, Wilson J, Vollenweider P, Shuldiner A, Staessen J, Steinthorsdottir V, Stolk R, Strauch K, Tönjes A, Tremblay A, Tremoli E, Vohl M, Völker U, Dedoussis G, Ferrucci L, Oostra B, Palmer C, Pedersen N, Perola M, Pérusse L, Peters U, Power C, Quertermous T, Rauramaa R, Rivadeneira F, Njølstad I, Munroe P, März W, Froguel P, Grabe H, Hamsten A, Hui J, Hveem K, Jöckel K, Kivimäki M, Kuh D, Laakso M, Liu Y, Saaristo T, Montgomery G, Pasko D, Bandinelli S, Barrett A, Bellis C, Bennett A, Berne C, Blüher M, Böhringer S, Bonnet F, Böttcher Y, Bruinenberg M, Arscott G, Arnlöv J, Albrecht E, Pechlivanis S, Peters M, Prokopenko I, Stančáková A, Sung Y, Tanaka T, Teumer A, van Vliet-Ostaptchouk J, Yengo L, Zhang W, Carba D, Caspersen I, Gigante B, Go A, Golay A, Grallert H, Grammer T, Gräßler J, Grewal J, Groves C, Haller T, Hallmans G, Giedraitis V, Garcia M, Friedrich N, Clarke R, Daw E, Deelen J, Deelman E, Delgado G, Doney A, Eklund N, Erdos M, Estrada K, Eury E, Hartman C, Palmer C, Shungin D, Roman T, Drong A, Song C, Gustafsson S, Day F, Esko T, Fall T, Kutalik Z, Luan J, Randall J, Heard-Costa N, Buchkovich M, Wu J, Winkler T, Croteau-Chonka D, Ferreira T, Locke A, Mägi R, Strawbridge R, Pers T, Fischer K, Justice A, Workalemahu T, Scherag A, Vedantam S, Demirkan A, Ehret G, Feitosa M, Goel A, Jackson A, Johnson T, Kleber M, Kristiansson K, Mangino M, Leach I, Buyske S, Bragg-Gresham J, Beekman M, Wood A, Chen J, Fehrmann R, Karjalainen J, Kahali B, Liu C, Schmidt E, Absher D, Amin N, Anderson D, Medina-Gomez C, Hassinen M, Rose L, Tayo B, Thorand B, Thorleifsson G, Tomaschitz A, Troffa C, van Oort F, Verweij N, Vonk J, Waite L, Wennauer R, Syvänen A, Swift A, Swertz M, Sanna S, Scharnagl H, Scholtens S, Sennblad B, Seufferlein T, Sitlani C, Smith A, Stirrups K, Stringham H, Sundstrom J, Wilsgaard T, Wojczynski M, Karpe F, Keildson S, Kiryluk K, Liang L, Lifton R, Ma B, McKnight A, McPherson R, Metspalu A, Min J, Kanoni S, Huang J, Hivert M, Wong A, Zhang Q, Zhao J, Brennan E, Choi M, Eriksson P, Folkersen L, Franco-Cereceda A, Gharavi A, Hedman Å, Moffatt M, Robertson N, Hayward C, Koenig W, Kooner I, Kratzer W, Lamina C, Leander K, Lee N, Lichtner P, Lind L, Lindström J, Lobbens S, Kinnunen L, Kalafati I, Juliusdottir T, Heikkilä K, Herzig K, Helmer Q, Hillege H, Holmen O, Hunt S, Isaacs A, Ittermann T, James A, Johansson I, Lorentzon M, Mach F, Müller G, Müller-Nurasyid M, Nagaraja R, Nalls M, Narisu N, Glorioso N, Nolte I, Olden M, Rayner N, Renström F, Mulas A, Mühleisen T, Mooijaart S, Magnusson P, Mahajan A, McArdle W, Menni C, Merger S, Mihailov E, Milani L, Mills R, Moayyeri A, Monda K, Ried J. New genetic loci link adipose and insulin biology to body fat distribution. Nature 2015; 518:187-196.

Type

Journal Paper/Review (English)

Journal

Nature 2015; 518

Publication Date

Feb 12, 2015

Issn Electronic

1476-4687

Pages

187-196

Brief description/objective

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.