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

D Shungin, TW Winkler, DC Croteau-Chonka, T Ferreira, AE Lockes, R Magi, RJ Strawbridge, TH Pers, K (Kirsten) Fischer, AE Justice, T Workalemahu, JMW Wu, ML Buchkovich, NL Heard-Costa, TS Roman, AW Drong, C Song, S Gustafsson, FR Day, T EskoT Fall, Z Kutalik, JA Luan, JC Randall, A Scherag, S Vedantam, AR Wood, J Chen, R Fehrmann, J Karjalainen, B Kahali, CT Liu, EM Schmidt, D Absher, Najaf Amin, D Anderson, M Beekman, JL Bragg-Gresham, S Buyske, Ayse Demirkan, GB Ehret, MF Feitosa, A Goel, AU Jackson, T Johnson, ME Kleber, K Kristiansson, M Mangino, IM Leach, C Medina-Gomez, CD Palmer, D Pasko, S Pechlivaniss, Marjolein Peters, I Prokopenko, A Stancakova, YJ Sung, T Tanakam, A Teumer, JV van Vliet-Ostaptchouk, L Yengo, WH Zhang, E Albrecht, J Arnlov, GM Arscott, S Bandinelli, A Barrett, C Bellis, AJ Bennett, C Berne, M Bluher, S Buhringer, F Bonnet, Y Bottcher, M Bruinenberg, DB Carba, IH Caspersen, R Clarke, EW Daw, J Deelen, E Deelman, G Delgado, ASF Doney, N Eklund, MR Erdos, Karol Estrada Gil, E Eury, N Friedrichs, ME Garcia, V Giedraitis, B Gigante, AS Go, A Golay, H Grallert, TB Grammer, J Grassler, J Grewal, CJ Groves, T Haller, G Hallmans, CA Hartman, M Hassinen, C Hayward, K Heikkila, KH Herzig, Q Helmer, HL Hillege, O Holmen, SC Hunt, Aaron Isaacs, T Ittermann, AL James, I Johansson, T Juliusdottir, IP Kalafati, L Kinnunen, W Koenig, IK Kooner, W Kratzer, C Lamina, K Leander, NR Lee, P Lichtner, L Lind, J Lindstrom, S Lobbens, M Lorentzon, F Mach, PKE Magnusson, A Mahajan, WL McArdle, C Menni, S Merger, E Mihailov, L Milani, R Mills, A Moayyeri, KL Monda, SP Mooijaart, TW Muhleisen, A Mulas, G Muller, M Muller-Nurasyid, R Nagaraja, MA Nalls, N Narisu, N Glorioso, IM (Ilja) Nolte, M Olden, NW Rayner, F Renstrom, JS Ried, NR Robertson, LM Rose, S Sanna, H Scharnagl, s Scholtens, B Sennblad, T Seufferlein, CM Sitlani, AV Smith, K Stirrups, HM Stringhams, J Sundstrom, MA Swertz, AJ Swift, AC Syvanen, BO Tayo, B Thorand, G Thorleifsson, A Tomaschitz, C Troffa, Floor Oort, N (Niek) Verweij, JM Vonk, LL Waite, R Wennauer, T Wilsgaard, MK Wojczynski, A Wong, QY Zhang, JH Zhao, EP Brennan, M Choi, P Eriksson, L Folkersen, A Franco-Cereceda, AG Gharavi, AK Hedman, MF Hivert, JY Huang, S Kanoni, F Karpe, S Keildson, K Kiryluk, LM Liang, RP Lifton, BS Ma, AJ McKnight, R McPherson, A Metspalu, JL Min, MF Moffatt, GW Montgomery, JM Murabito, G Nicholson, DR Nyholt, C Olsson, JRB Perry, E Reinmaa, RM Salem, N Sandholm, EE Schadt, R Scott, Lisette Stolk, EE Vallejo, HJ Westra, KT Zondervan, P Amouyel, D Arveiler, SJL Bakker, J Beilby, RN Bergman, J Blangero, MJ Brown, M Burnier, H Campbell, A Chakravarti, PS Chiness, S Claudi-Boehmi, FS Collins, DC Crawford, J Danesh, U de Faire, EJC de Geusl, M Dorr, R Erbel, JG Eriksson, M Farrall, E Ferrannini, J Ferrieres, NG Forouhi, T Forrester, OH Franco Duran, RT Gansevoort, C Gieger, V Gudnason, CA Haiman, TB Harris, AT Hattersley, M Heliovaara, AA Hicks, AD Hingorani, W Hoffmann, Bert Hofman, G Homuth, SE Humphries, E Hypponen, T Illig, MR Jarvelin, B Johansen, P Jousilahti, AM Jula, J Kaprio, F Kee, SM Keinanen-Kiukaanniemi, JS Kooner, C Kooperberg, P Kovacs, AT Kraja, M Kumari, K Kuulasmaa, J Kuusisto, TA Lakka, C Langenberg, L Le Marchand, T Lehtimaki, V Lyssenko, S Mannisto, A Marette, TC Matise, CA McKenzie, B McKnight, AW Musk, S Mohlenkamp, AD Morris, M Nelis, C Ohlsson, AJ (A.) Oldehinkel, KK Ong, LJ Palmer, BW Penninx, A Peters, PP Pramstaller, OT Raitakari, T Rankinen, DC Rao, TK Rice, PM Ridker, MD Ritchie, I Rudan, V Salomaa, NJ Samani, J Saramies, MA Sarzynski, PEH Schwarz, AR Shuldiner, JA Staessen, V Steinthorsdottir, RP (Ronald) Stolk, K Strauch, A Tonjes, A Tremblay, E Tremoli, MC Vohl, U Volker, P Vollenweider, JF Wilson, JCM Witteman, LS Adair, M Bochud, BO Boehm, SR Bornstein, C Bouchard, S Cauchi, MJ Caulfield, JC Chambers, DI Chasman, RS Cooper, G Dedoussis, L Ferrucci, P Froguel, HJ Grabe, A Hamsten, JN Hui, K Hveem, KH Jockel, M Kivimaki, D Kuh, M Laakso, YM Liu, W Marz, PB Munroe, I Njolstad, Ben Oostra, CNA Palmer, NL Pedersen, M Perola, L Perusse, U Peters, C Power, T Quertermous, R Rauramaa, Fernando Rivadeneira, TE Saaristo, D Saleheen, J Sinisalo, PE (Eline) Slagboom, H Snieder, TD Spector, UR Thorsteinsdottir, M Stumvoll, J Tuomilehto, André Uitterlinden, M Uusitupa, P van der Harst, G Veronesi, M Walker, NJ Wareham, H Watkins, HE Wichmann, GR Abecasis, TL Assimes, SI Berndt, M Boehnkes, IB Borecki, P Deloukas, L Franke, TM Frayling, LC Groop, DJ Hunter, RC Kaplan, JR O'Connell, L Qi, D Schlessinger, DP Strachan, K Stefansson, CM van Dujin, CJ Willer, PM Visscher, Jiaqi Yang, JN Hirschhorn, M.C. Zillikens, MI McCarthy, EK Speliotes, KE North, CS Fox, I Barroso, PW Franks, E Ingelsson, IM Heid, RJF Loos, LA Cupples, AP Morris, CM Lindgren, KL Mohlke

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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 x 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.
Original languageUndefined/Unknown
Pages (from-to)187-196
Number of pages10
JournalNature
Volume518
Issue number7538
DOIs
Publication statusPublished - 2015

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