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

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Authors: Shungin, D.; Winkler, T. W.; Croteau-Chonka, D. C.; Ferreira, T.; Locke, A. E.; Magi, R.; Strawbridge, R. J.; Pers, T. H.; Fischer, K; Justice, A. E.; Workalemahu, T.; Wu, J. M.; 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; Stancakova, A.; Ju Sung, Y.; Tanaka, T; Teumer, A; Van Vliet-Ostaptchouk, J. V.; Yengo, L; Zhang, W; Albrecht, E.; Arnlov, J.; Arscott, G. M.; Bandinelli, S; Barrett, A.; Bellis, C.; Bennett, A. J.; Berne, C.; Bluher, M.; Bohringer, S.; Bonnet, F.; Bottcher, Y.; Bruinenberg, M; Carba, D. B.; Caspersen, I. H.; Clarke, R.; Daw, E. W.; Deelen, J.; Deelman, E.; Delgado, G; Doney, A. S.; 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.; Grassler, J.; Grewal, J.; Groves, C. J.; Haller, T; Hallmans, G; Hartman, C. A.; Hassinen, M; Hayward, C; Heikkila, 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; Lindstrom, J.; Lobbens, S; Lorentzon, M; Mach, F.; Magnusson, P. K.; Mahajan, A; McArdle, W. L.; Menni, C; Merger, S.; Mihailov, E; Milani, L; Mills, R.; Moayyeri, A.; Monda, K. L.; Mooijaart, S. P.; Muhleisen, T. W.; Mulas, A.; Muller, G.; Muller-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.; Sundstrom, J.; Swertz, M. A.; Swift, A. J.; Syvanen, A. C.; Tayo, B. O.; Thorand, B; Thorleifsson, G; Tomaschitz, A.; Troffa, C.; van Oort, F. V.; 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, A. 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.; Reinmaa, E.; Salem, R. M.; Sandholm, N.; Schadt, E. E.; Scott, R. A.; Stolk, L.; Vallejo, E. E.; Westra, H. J.; Zondervan, K. T.; ADIPOGen Consortium; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GEFOS Consortium; GENIE Consortium; GLGC; ICBP; International Endogene Consortium; Lifelines Cohort Study; MAGIC Investigators; MuTHER Consortium; PAGE Consortium; ReproGen Consortium; Amouyel, P.; Arveiler, D.; Bakker, S. J.; 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.; Dorr, M.; Erbel, R.; Eriksson, J. G.; Farrall, M; Ferrannini, E.; Ferrieres, 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.; Heliovaara, M.; Hicks, A. A.; Hingorani, A. D.; Hoffmann, W.; Hofman, A; Homuth, G; Humphries, S. E.; Hypponen, 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; Lehtimaki, T.; Lyssenko, V.; Mannisto, S.; Marette, A.; Matise, T. C.; McKenzie, C. A.; McKnight, B; Musk, A. W.; Mohlenkamp, 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.; Shuldiner, A. R.; Staessen, J. A.; Steinthorsdottir, V.; Stolk, R. P.; Strauch, K; Tonjes, A.; Tremblay, A.; Tremoli, E; Vohl, M. C.; Volker, 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; Jockel, K. H.; Kivimaki, M; Kuh, D; Laakso, M; Liu, Y; Marz, W.; Munroe, P. B.; Njolstad, I.; Oostra, B. A.; Palmer, C. N.; Pedersen, N. L.; Perola, M; Perusse, 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.; Cupples, L. A.; Morris, A. P.; Lindgren, C. M.; Mohlke, K. L.
Article Title: New genetic loci link adipose and insulin biology to body fat distribution
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.
Journal Title: Nature
Volume: 518
Issue: 7538
ISSN: 1476-4687; 0028-0836
Publisher: Unknown  
Journal Place: England
Date Published: 2015
Start Page: 187
End Page: 196
Language: eng
DOI/URL:

10.1038/nature14132
Notes: JID: 0410462; 2013/11/20 [received]; 2014/12/02 [accepted]; ppublish