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

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.; J. M. . W., 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.; 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.; Leach, I.M.; Medina Gomez, C.; Palmer, C.D.; Pasko, D.; Pechlivanis, S.; Peters, M.J.; Prokopenko, I.; Stanca'Kova', A.; Sung, Y.J.; 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.; A. S., G.; Golay, A.; Grallert, H.; Grammer, T.B.; Gräsler, J.; Grewal, J.; Groves, C.J.; Haller, T.; Hallmans, G.; Hartman, C.A.; Hassinen, M.; Hayward, C.; Heikkilä, K.; Herzig, K.; Helmer, Q.; Hillege, H.L.; Holmen, O.; Hunt, S.C.; Isaacs, A.; Ittermann, T.; James, A.L.; Johansson, I.; Juliusdottir, T.; Kalafati, I.; 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.; Smith, A.V.; Stirrups, K.; Stringham, H.M.; Sundström, J.; Swertz, M.A.; Swift, A.J.; Syvänen, A.; 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.; Zhao, J.H.; Brennan, E.P.; Choi, M.; Eriksson, P.; Folkersen, L.; Franco Cereceda, A.; Gharavi, A.G.; Hedman, A.K.; Hivert, M.; 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.; 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.; 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.; 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.; Hamsten, A.; Hui, J.; Hveem, K.; Jöckel, K.; Kivimaki, M.; Kuh, D.; Laakso, M.; Liu, Y.; März, W.; Munroe, P.B.; Njolstad, I.; Oostra, B.A.; Palmer, C.N..A.; Pedersen, N.L.; Perola, M.; Pe'Russe, 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.; 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.

doi:10.1038/nature14132

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.

New genetic loci link adipose and insulin biology to body fat distribution / D. Shungin, T.W. Winkler, D.C. Croteau-Chonka, T. Ferreira, A.E. Locke, R. Mägi, R.J. Strawbridge, T.H. Pers, K. Fischer, A.E. Justice, T. Workalemahu, J.M..W. Wu, M.L. Buchkovich, N.L. Heard-Costa, T.S. Roman, A.W. Drong, C. Song, S. Gustafsson, F.R. Day, T. Esko, T. Fall, Z. Kutalik, J. Luan, J.C. Randall, A. Scherag, S. Vedantam, A.R. Wood, J. Chen, R. Fehrmann, J. Karjalainen, B. Kahali, C. Liu, E.M. Schmidt, D. Absher, N. Amin, D. Anderson, M. Beekman, J.L. Bragg-Gresham, S. Buyske, A. Demirkan, G.B. Ehret, M.F. Feitosa, A. Goel, A.U. Jackson, T. Johnson, M.E. Kleber, K. Kristiansson, M. Mangino, I.M. Leach, C. Medina-Gomez, C.D. Palmer, D. Pasko, S. Pechlivanis, M.J. Peters, I. Prokopenko, A. Stanca'Kova', Y.J. Sung, T. Tanaka, A. Teumer, J.V. Van Vliet-Ostaptchouk, L. Yengo, W. Zhang, E. Albrecht, J. Ärnlöv, G.M. Arscott, S. Bandinelli, A. Barrett, C. Bellis, A.J. Bennett, C. Berne, M. Blüher, S. Böhringer, F. Bonnet, Y. Böttcher, M. Bruinenberg, D.B. Carba, I.H. Caspersen, R. Clarke, E..W. Daw, J. Deelen, E. Deelman, G. Delgado, A.S..F. Doney, N. Eklund, M.R. Erdos, K. Estrada, E. Eury, N. Friedrich, M.E. Garcia, V. Giedraitis, B. Gigante, A.S. Go, A. Golay, H. Grallert, T.B. Grammer, J. Gräsler, J. Grewal, C.J. Groves, T. Haller, G. Hallmans, C.A. Hartman, M. Hassinen, C. Hayward, K. Heikkilä, K. Herzig, Q. Helmer, H.L. Hillege, O. Holmen, S.C. Hunt, A. Isaacs, T. Ittermann, A.L. James, I. Johansson, T. Juliusdottir, I. Kalafati, L. Kinnunen, W. Koenig, I.K. Kooner, W. Kratzer, C. Lamina, K. Leander, N.R. Lee, P. Lichtner, L. Lind, J. Lindström, S. Lobbens, M. Lorentzon, F. Mach, P.K..E. Magnusson, A. Mahajan, W.L. Mcardle, C. Menni, S. Merger, E. Mihailov, L. Milani, R. Mills, A. Moayyeri, K.L. Monda, S.P. Mooijaart, T.W. Mühleisen, A. Mulas, G. Müller, M. Müller-Nurasyid, R. Nagaraja, M.A. Nalls, N. Narisu, N. Glorioso, I.M. Nolte, M. Olden, N.W. Rayner, F. Renstrom, J.S. Ried, N.R. Robertson, L.M. Rose, S. Sanna, H. Scharnagl, S. Scholtens, B. Sennblad, T. Seufferlein, C.M. Sitlani, A.V. Smith, K. Stirrups, H.M. Stringham, J. Sundström, M.A. Swertz, A.J. Swift, A. Syvänen, B.O. Tayo, B. Thorand, G. Thorleifsson, A. Tomaschitz, C. Troffa, F.V..A. Van Oort, N. Verweij, J.M. Vonk, L.L. Waite, R. Wennauer, T. Wilsgaard, M.K. Wojczynski, A. Wong, Q. Zhang, J.H. Zhao, E.P. Brennan, M. Choi, P. Eriksson, L. Folkersen, A. Franco-Cereceda, A.G. Gharavi, A.K. Hedman, M. Hivert, J. Huang, S. Kanoni, F. Karpe, S. Keildson, K. Kiryluk, L. Liang, R.P. Lifton, B. Ma, A.J. Mcknight, R. Mcpherson, A. Metspalu, J.L. Min, M.F. Moffatt, G.W. Montgomery, J.M. Murabito, G. Nicholson, D.R. Nyholt, C. Olsson, J.R..B. Perry, E. Reinmaa, R.M. Salem, N. Sandholm, E.E. Schadt, R.A. Scott, L. Stolk, E.E. Vallejo, H. Westra, K.T. Zondervan, P. Amouyel, D. Arveiler, S.J..L. Bakker, J. Beilby, R.N. Bergman, J. Blangero, M.J. Brown, M. Burnier, H. Campbell, A. Chakravarti, P.S. Chines, S. Claudi-Boehm, F.S. Collins, D.C. Crawford, J. Danesh, U. De Faire, E.J..C. De Geus, M. Dörr, R. Erbel, J.G. Eriksson, M. Farrall, E. Ferrannini, J. Ferrières, N.G. Forouhi, T. Forrester, O.H. Franco, R.T. Gansevoort, C. Gieger, V. Gudnason, C.A. Haiman, T.B. Harris, A.T. Hattersley, M. Heliövaara, A.A. Hicks, A.D. Hingorani, W. Hoffmann, A. Hofman, G. Homuth, S.E. Humphries, E. Hyppönen, T. Illig, M. Jarvelin, B. Johansen, P. Jousilahti, A.M. Jula, J. Kaprio, F. Kee, S.M. Keinanen-Kiukaanniemi, J.S. Kooner, C. Kooperberg, P. Kovacs, A.T. Kraja, M. Kumari, K. Kuulasmaa, J. Kuusisto, T.A. Lakka, C. Langenberg, L. Le Marchand, T. Lehtimäki, V. Lyssenko, S. Männistö, A. Marette, T.C. Matise, C.A. Mckenzie, B. Mcknight, A.W. Musk, S. Möhlenkamp, A.D. Morris, M. Nelis, C. Ohlsson, A.J. Oldehinkel, K.K. Ong, L.J. Palmer, B.W. Penninx, A. Peters, P.P. Pramstaller, O.T. Raitakari, T. Rankinen, D.C. Rao, T.K. Rice, P.M. Ridker, M.D. Ritchie, I. Rudan, V. Salomaa, N.J. Samani, J. Saramies, M.A. Sarzynski, P.E..H. Schwarz, A.R. Shuldiner, J.A. Staessen, V. Steinthorsdottir, R.P. Stolk, K. Strauch, A. Tönjes, A. Tremblay, E. Tremoli, M. Vohl, U. Völker, P. Vollenweider, J.F. Wilson, J.C. Witteman, L.S. Adair, M. Bochud, B.O. Boehm, S.R. Bornstein, C. Bouchard, S. Cauchi, M.J. Caulfield, J.C. Chambers, D.I. Chasman, R.S. Cooper, G. Dedoussis, L. Ferrucci, P. Froguel, H. Grabe, A. Hamsten, J. Hui, K. Hveem, K. Jöckel, M. Kivimaki, D. Kuh, M. Laakso, Y. Liu, W. März, P.B. Munroe, I. Njolstad, B.A. Oostra, C.N..A. Palmer, N.L. Pedersen, M. Perola, L. Pe'Russe, U. Peters, C. Power, T. Quertermous, R. Rauramaa, F. Rivadeneira, T.E. Saaristo, D. Saleheen, J. Sinisalo, P..E. Slagboom, H. Snieder, T.D. Spector, U. Thorsteinsdottir, M. Stumvoll, J. Tuomilehto, A.G. Uitterlinden, M. Uusitupa, P. Van Der Harst, G. Veronesi, M. Walker, N.J. Wareham, H. Watkins, H. Wichmann, G.R. Abecasis, T.L. Assimes, S.I. Berndt, M. Boehnke, I.B. Borecki, P. Deloukas, L. Franke, T.M. Frayling, L.C. Groop, D.J. Hunter, R.C. Kaplan, J.R. O'Connell, L. Qi, D. Schlessinger, D.P. Strachan, K. Stefansson, C.M. Van Duijn, C.J. Willer, P.M. Visscher, J. Yang, J.N. Hirschhorn, M..C. Zillikens, M.I. Mccarthy, E.K. Speliotes, K.E. North, C.S. Fox, I. Barroso, P.W. Franks, E. Ingelsson, I.M. Heid, R.J..F. Loos, L..A. Cupples, A.P. Morris, C.M. Lindgren, K.L. Mohlke. - In: NATURE. - ISSN 0028-0836. - 518:7538(2015 Feb), pp. 187-197. [10.1038/nature14132]

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

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

2015

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.

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	Parole chiave
	
				Adipocytes; Adipogenesis; Adipose Tissue; Age Factors; Body Mass Index; Continental Population Groups; Epigenesis, Genetic; Europe; Female; Genome, Human; Humans; Insulin; Insulin Resistance; Male; Models, Biological; Neovascularization, Physiologic; Obesity; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Sex Characteristics; Transcription, Genetic; Waist-Hip Ratio; Body Fat Distribution; Genome-Wide Association Study; Multidisciplinary
			
	Settori scientifico-disciplinari dell'articolo
	
				Settore BIO/18 - Genetica
			
	Data di pubblicazione
	
				feb-2015
			
	Rivista in ANCE
	
				NATURE
			
	DOI
	
				https://dx.doi.org/10.1038/nature14132
			
	Tipologia
	
				Article (author)
			
	Appare nelle tipologie:
	
				01 - Articolo su periodico

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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/282822

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