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

Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Locke, Adam E, Magi, Reedik, Strawbridge, Rona J, Pers, Tune H, Fischer, Krista, Justice, Anne E, Workalemahu, Tsegaselassie, Wu, Joseph M.W, 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, Zoltan, Luan, Jian'an, Randall, Joshua C, Scherag, Andre, 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, George 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, Stanca'kova', Alena, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana, Yengo, Loic, Zhang, Weihua, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Bluher, Matthias, Bohringer, Stefan, Bonnet, Fabrice, Bottcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B, Caspersen, Ida H, Clarke, Robert, Daw, E. Warwick, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S.F, 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, Grasler, Jurgen, Grewal, Jagvir, Groves, Christopher J, Haller, Toomas, Hallmans, Goran, Hartman, Catharina A, Hassinen, Maija, Hayward, Caroline, Heikkila, 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, Lindstrom, Jaana, Lobbens, Stephane, Lorentzon, Mattias, Mach, Francois, Magnusson, Patrik K. E, Mahajan, Anubha, McArdle, Wendy L, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Keri L, Mooijaart, Simon P, Muhleisen, Thomas W, Mulas, Antonella, Muller, Gabriele, Muller-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, Sundstrom, Johan, Swertz, Morris A, Swift, Amy J, Syvanen, Anne-Christine, Tayo, Bamidele O, Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, Van Oort, Floor V.A, 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, Asa 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 R.B, Reinmaa, Eva, Salem, Rany M, Sandholm, Niina, Schadt, Eric E, Scott, Robert A, Stolk, Lisette, Vallejo, Edgar E, Westra, Harm-Jan, Zondervan, Krina T, Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan J.L, 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 J.C, Dorr, Marcus, Erbel, Raimund, Eriksson, Johan G, Farrall, Martin, Ferrannini, Ele, Ferrieres, 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, Heliovaara, Markku, Hicks, Andrew A, Hingorani, Aroon D, Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E, Hypponen, 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, Lehtimaki, Terho, Lyssenko, Valeriya, Mannisto, Satu, Marette, Andre, Matise, Tara C, McKenzie, Colin A, McKnight, Barbara, Musk, Arthur W, Mohlenkamp, 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, D.C, Rice, Treva K, Ridker, Paul M, Ritchie, Marylyn D, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Saramies, Jouko, Sarzynski, Mark A, Schwarz, Peter E.H, Shuldiner, Alan R, Staessen, Jan A, Steinthorsdottir, Valgerdur, Stolk, Ronald P, Strauch, Konstantin, Tonjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Volker, Uwe, Vollenweider, Peter, Wilson, James F, Witteman, Jacqueline C, Adair, Linda S, Bochud, Murielle, Boehm, Bernhard O, Bornstein, Stefan R, Bouchard, Claude, Cauchi, Stephane, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Cooper, Richard S, Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Jorgen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Jockel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Marz, Winfried, Munroe, Patricia B, Njolstad, Inger, Oostra, Ben A, Palmer, Colin N.A, Pedersen, Nancy L, Perola, Markus, Pe'russe, 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, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, Andre 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, Stefansson, Kari, 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, Ines, Franks, Paul W, Ingelsson, Erik, Heid, Iris M, Loos, Ruth J.F, Cupples, L, Morris, Andrew P, Lindgren, Cecilia M and Mohlke, Karen L (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518 7538: 187-196. doi:10.1038/nature14132


Author Shungin, Dmitry
Winkler, Thomas W
Croteau-Chonka, Damien C
Ferreira, Teresa
Locke, Adam E
Magi, Reedik
Strawbridge, Rona J
Pers, Tune H
Fischer, Krista
Justice, Anne E
Workalemahu, Tsegaselassie
Wu, Joseph M.W
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, Zoltan
Luan, Jian'an
Randall, Joshua C
Scherag, Andre
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, George 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
Stanca'kova', Alena
Sung, Yun Ju
Tanaka, Toshiko
Teumer, Alexander
Van Vliet-Ostaptchouk, Jana
Yengo, Loic
Zhang, Weihua
Albrecht, Eva
Arnlov, Johan
Arscott, Gillian M
Bandinelli, Stefania
Barrett, Amy
Bellis, Claire
Bennett, Amanda J
Berne, Christian
Bluher, Matthias
Bohringer, Stefan
Bonnet, Fabrice
Bottcher, Yvonne
Bruinenberg, Marcel
Carba, Delia B
Caspersen, Ida H
Clarke, Robert
Daw, E. Warwick
Deelen, Joris
Deelman, Ewa
Delgado, Graciela
Doney, Alex S.F
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
Grasler, Jurgen
Grewal, Jagvir
Groves, Christopher J
Haller, Toomas
Hallmans, Goran
Hartman, Catharina A
Hassinen, Maija
Hayward, Caroline
Heikkila, 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
Lindstrom, Jaana
Lobbens, Stephane
Lorentzon, Mattias
Mach, Francois
Magnusson, Patrik K. E
Mahajan, Anubha
McArdle, Wendy L
Menni, Cristina
Merger, Sigrun
Mihailov, Evelin
Milani, Lili
Mills, Rebecca
Moayyeri, Alireza
Monda, Keri L
Mooijaart, Simon P
Muhleisen, Thomas W
Mulas, Antonella
Muller, Gabriele
Muller-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
Sundstrom, Johan
Swertz, Morris A
Swift, Amy J
Syvanen, Anne-Christine
Tayo, Bamidele O
Thorand, Barbara
Thorleifsson, Gudmar
Tomaschitz, Andreas
Troffa, Chiara
Van Oort, Floor V.A
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, Asa 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 R.B
Reinmaa, Eva
Salem, Rany M
Sandholm, Niina
Schadt, Eric E
Scott, Robert A
Stolk, Lisette
Vallejo, Edgar E
Westra, Harm-Jan
Zondervan, Krina T
Amouyel, Philippe
Arveiler, Dominique
Bakker, Stephan J.L
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 J.C
Dorr, Marcus
Erbel, Raimund
Eriksson, Johan G
Farrall, Martin
Ferrannini, Ele
Ferrieres, 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
Heliovaara, Markku
Hicks, Andrew A
Hingorani, Aroon D
Hoffmann, Wolfgang
Hofman, Albert
Homuth, Georg
Humphries, Steve E
Hypponen, 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
Lehtimaki, Terho
Lyssenko, Valeriya
Mannisto, Satu
Marette, Andre
Matise, Tara C
McKenzie, Colin A
McKnight, Barbara
Musk, Arthur W
Mohlenkamp, 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, D.C
Rice, Treva K
Ridker, Paul M
Ritchie, Marylyn D
Rudan, Igor
Salomaa, Veikko
Samani, Nilesh J
Saramies, Jouko
Sarzynski, Mark A
Schwarz, Peter E.H
Shuldiner, Alan R
Staessen, Jan A
Steinthorsdottir, Valgerdur
Stolk, Ronald P
Strauch, Konstantin
Tonjes, Anke
Tremblay, Angelo
Tremoli, Elena
Vohl, Marie-Claude
Volker, Uwe
Vollenweider, Peter
Wilson, James F
Witteman, Jacqueline C
Adair, Linda S
Bochud, Murielle
Boehm, Bernhard O
Bornstein, Stefan R
Bouchard, Claude
Cauchi, Stephane
Caulfield, Mark J
Chambers, John C
Chasman, Daniel I
Cooper, Richard S
Dedoussis, George
Ferrucci, Luigi
Froguel, Philippe
Grabe, Hans-Jorgen
Hamsten, Anders
Hui, Jennie
Hveem, Kristian
Jockel, Karl-Heinz
Kivimaki, Mika
Kuh, Diana
Laakso, Markku
Liu, Yongmei
Marz, Winfried
Munroe, Patricia B
Njolstad, Inger
Oostra, Ben A
Palmer, Colin N.A
Pedersen, Nancy L
Perola, Markus
Pe'russe, 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
Thorsteinsdottir, Unnur
Stumvoll, Michael
Tuomilehto, Jaakko
Uitterlinden, Andre 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
Stefansson, Kari
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, Ines
Franks, Paul W
Ingelsson, Erik
Heid, Iris M
Loos, Ruth J.F
Cupples, L
Morris, Andrew P
Lindgren, Cecilia M
Mohlke, Karen L
Title New genetic loci link adipose and insulin biology to body fat distribution
Journal name Nature   Check publisher's open access policy
ISSN 1476-4687
0028-0836
Publication date 2015-02-12
Year available 2015
Sub-type Article (original research)
DOI 10.1038/nature14132
Open Access Status Not yet assessed
Volume 518
Issue 7538
Start page 187
End page 196
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
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.
Formatted 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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
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Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
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