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Open Access Publications from the University of California

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

  • Author(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 MW
  • 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
  • Leach, Irene Mateo
  • Medina-Gomez, Carolina
  • Palmer, Cameron D
  • Pasko, Dorota
  • Pechlivanis, Sonali
  • Peters, Marjolein J
  • Prokopenko, Inga
  • Stančáková, Alena
  • Sung, Yun Ju
  • 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 Sf
  • 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 Ke
  • 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
  • Smith, Albert Vernon
  • 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 Va
  • Verweij, Niek
  • Vonk, Judith M
  • Waite, Lindsay L
  • Wennauer, Roman
  • Wilsgaard, Tom
  • Wojczynski, Mary K
  • 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
  • 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 Rb
  • Reinmaa, Eva
  • Salem, Rany M
  • Sandholm, Niina
  • Schadt, Eric E
  • Scott, Robert A
  • Stolk, Lisette
  • Vallejo, Edgar E
  • Westra, Harm-Jan
  • Zondervan, Krina 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, Philippe
  • Arveiler, Dominique
  • Bakker, Stephan Jl
  • 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 Jc
  • 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, DC
  • Rice, Treva K
  • Ridker, Paul M
  • Ritchie, Marylyn D
  • Rudan, Igor
  • Salomaa, Veikko
  • Samani, Nilesh J
  • Saramies, Jouko
  • Sarzynski, Mark A
  • Schwarz, Peter Eh
  • 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 Na
  • 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
  • Stefansson, Kari
  • 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
  • Thorsteinsdottir, Unnur
  • 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 Jf
  • Cupples, L Adrienne
  • Morris, Andrew P
  • Lindgren, Cecilia M
  • Mohlke, Karen L
  • et al.
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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