Titre
Common variants near MC4R are associated with fat mass, weight and risk of obesity.
Type
Institution
Périodique
Nature Genetics
Auteur(s)
Loos, R.J.
Lindgren, C.M.
Li, S.
Wheeler, E.
Zhao, J.H.
Prokopenko, I.
Inouye, M.
Freathy, R.M.
Attwood, A.P.
Beckmann, J.S.
Berndt, S.I.
Prostate Lung, Colorectal
Jacobs, K.B.
Jacobs, K.B.
Chanock, S.J.
Hayes, R.B.
Bergmann, S.
Bennett, A.J.
Bingham, S.A.
Bochud, M.
Brown, M.
Cauchi, S.
Connell, J.M.
Cooper, C.
Smith, G.D.
Day, I.
Dina, C.
De, S.
Dermitzakis, E.T.
Doney, A.S.
Elliott, K.S.
Elliott, P.
Evans, D.M.
Sadaf Farooqi, I.
Froguel, P.
Ghori, J.
Groves, C.J.
Gwilliam, R.
Hadley, D.
Hall, A.S.
Hattersley, A.T.
Hebebrand, J.
Heid, I.M.
Lamina, C.
Lamina, C.
Gieger, C.
Illig, T.
Meitinger, T.
Wichmann, H.E.
Herrera, B.
Hinney, A.
Hunt, S.E.
Jarvelin, M.R.
Johnson, T.
Jolley, J.D.
Karpe, F.
Keniry, A.
Khaw, K.T.
Luben, R.N.
Mangino, M.
Marchini, J.
McArdle, W.L.
McGinnis, R.
Meyre, D.
Munroe, P.B.
Morris, A.D.
Ness, A.R.
Neville, M.J.
Nica, A.C.
Ong, K.K.
O'Rahilly, S.
Owen, K.R.
Palmer, C.N.
Papadakis, K.
Potter, S.
Pouta, A.
Qi, L.
Randall, J.C.
Randall, J.C.
Rayner, N.W.
Ring, S.M.
Sandhu, M.S.
Scherag, A.
Sims, M.A.
Song, K.
Soranzo, N.
Speliotes, E.K.
Syddall, H.E.
Syddall, H.E.
Teichmann, S.A.
Timpson, N.J.
Tobias, J.H.
Uda, M.
Vogel, C.I.
Vogel, C.I.
Wallace, C.
Waterworth, D.M.
Weedon, M.N.
Willer, C.J.
Willer, C.J.
Wraight, X.
Wraight, X.
Yuan, X.
Zeggini, E.
Hirschhorn, J.N.
Strachan, D.P.
Ouwehand, W.H.
Caulfield, M.J.
Samani, N.J.
Frayling, T.M.
Vollenweider, P.
Waeber, G.
Mooser, V.
Deloukas, P.
McCarthy, M.I.
Wareham, N.J.
Barroso, I.
Jacobs, K.B.
Chanock, S.J.
Hayes, R.B.
Lamina, C.
Gieger, C.
Illig, T.
Meitinger, T.
Wichmann, H.E.
Kraft, P.
Hankinson, S.E.
Hunter, D.J.
Hu, F.B.
Lyon, H.N.
Voight, B.F.
Ridderstrale, M.
Groop, L.
Scheet, P.
Sanna, S.
Abecasis, G.R.
Albai, G.
Nagaraja, R.
Schlessinger, D.
Jackson, A.U.
Tuomilehto, J.
Collins, F.S.
Boehnke, M.
Mohlke, K.L.
Contributrices/contributeurs
Prostate Lung, Colorectal
KORA, X.
FUSION, X.
Burton, PR.
Clayton, DG.
Cardon, LR.
Craddock, N.
Deloukas, P.
Duncanson, A.
Kwiatkowski, DP.
McCarthy, MI.
Ouwehand, WH.
Samani, NJ.
Todd, JA.
Donnelly, P.
Barrett, JC.
Burton, PR.
Davison, D.
Donnelly, P.
Easton, D.
Evans, DM.
Leung, HT.
Marchini, JL.
Morris, AP.
Spencer, CC.
Tobin, MD.
Cardon, LR.
Clayton, DG.
Attwood, AP.
Boorman, JP.
Cant, B.
Everson, U.
Hussey, JM.
Jolley, JD.
Knight, AS.
Koch, K.
Meech, E.
Nutland, S.
Prowse, CV.
Stevens, HE.
Taylor, NC.
Walters, GR.
Walker, NM.
Watkins, NA.
Winzer, T.
Todd, JA.
Ouwehand, WH.
Jones, RW.
McArdle, WL.
Ring, SM.
Strachan, DP.
Pembrey, M.
Breen, G.
St Clair, D.
Caesar, S.
Gordon-Smith, K.
Jones, L.
Fraser, C.
Green, EK.
Grozeva, D.
Hamshere, ML.
Holmans, PA.
Jones, IR.
Kirov, G.
Moskvina, V.
Nikolov, I.
O'Donovan, MC.
Owen, MJ.
Craddock, N.
Collier, DA.
Elkin, A.
Farmer, A.
Williamson, R.
McGuffin, P.
Young, AH.
Ferrier, IN.
Ball, SG.
Balmforth, AJ.
Barrett, JH.
Bishop, DT.
Iles, MM.
Maqbool, A.
Yuldasheva, N.
Hall, AS.
Braund, PS.
Burton, PR.
Dixon, RJ.
Mangino, M.
Stevens, S.
Tobin, MD.
Thompson, JR.
Samani, NJ.
Bredin, F.
Tremelling, M.
Parkes, M.
Drummond, H.
Lees, CW.
Nimmo, ER.
Satsangi, J.
Fisher, SA.
Forbes, A.
Lewis, CM.
Onnie, CM.
Prescott, NJ.
Sanderson, J.
Mathew, CG.
Barbour, J.
Mohiuddin, MK.
Todhunter, CE.
Mansfield, JC.
Ahmad, T.
Cummings, FR.
Jewell, DP.
Webster, J.
Brown, MJ.
Clayton, DG.
Lathrop, GM.
Connell, J.
Dominiczak, A.
Samani, NJ.
Marcano, CA.
Burke, B.
Dobson, R.
Gungadoo, J.
Lee, KL.
Munroe, PB.
Newhouse, SJ.
Onipinla, A.
Wallace, C.
Xue, M.
Caulfield, M.
Farrall, M.
Barton, A.
Bruce, IN.
Donovan, H.
Eyre, S.
Gilbert, PD.
Hider, SL.
Hinks, AM.
John, SL.
Potter, C.
Silman, AJ.
Symmons, DP.
Thomson, W.
Worthington, J.
Clayton, DG.
Dunger, DB.
Nutland, S.
Stevens, HE.
Walker, NM.
Widmer, B.
Todd, JA.
Frayling, TM.
Freathy, RM.
Lango, H.
Perry, JR.
Shields, BM.
Weedon, MN.
Hattersley, AT.
Hitman, GA.
Walker, M.
Elliott, KS.
Groves, CJ.
Lindgren, CM.
Rayner, NW.
Timpson, NJ.
Zeggini, E.
McCarthy, MI.
Newport, M.
Sirugo, G.
Lyons, E.
Vannberg, F.
Hill, AV.
Bradbury, LA.
Farrar, C.
Pointon, JJ.
Wordsworth, P.
Brown, MA.
Franklyn, JA.
Heward, JM.
Simmonds, MJ.
Gough, SC.
Seal, S.
Stratton, MR.
Rahman, N.
Ban, M.
Goris, A.
Sawcer, SJ.
Compston, A.
Conway, D.
Jallow, M.
Newport, M.
Sirugo, G.
Rockett, KA.
Kwiatkowski, DP.
Bumpstead, SJ.
Chaney, A.
Downes, K.
Ghori, MJ.
Gwilliam, R.
Hunt, SE.
Inouye, M.
Keniry, A.
King, E.
McGinnis, R.
Potter, S.
Ravindrarajah, R.
Whittaker, P.
Widden, C.
Withers, D.
Deloukas, P.
Leung, HT.
Nutland, S.
Stevens, HE.
Walker, NM.
Todd, JA.
Easton, D.
Clayton, DG.
Burton, PR.
Tobin, MD.
Barrett, JC.
Evans, DM.
Morris, AP.
Cardon, LR.
Cardin, NJ.
Davison, D.
Ferreira, T.
Pereira-Gale, J.
Hallgrimsdóttir, IB.
Howie, BN.
Marchini, JL.
Spencer, CC.
Su, Z.
Teo, YY.
Vukcevic, D.
Donnelly, P.
Bentley, D.
Brown, MA.
Cardon, LR.
Caulfield, M.
Clayton, DG.
Compston, A.
Craddock, N.
Deloukas, P.
Donnelly, P.
Farrall, M.
Gough, SC.
Hall, AS.
Hattersley, AT.
Hill, AV.
Kwiatkowski, DP.
Mathew, CG.
McCarthy, MI.
Ouwehand, WH.
Parkes, M.
Pembrey, M.
Rahman, N.
Samani, NJ.
Stratton, MR.
Todd, JA.
Worthington, J.
Groupes de travail
Ovarian (PLCO) Cancer Screening Trial
KORA
Nurses' Health Study
Diabetes Genetics Initiative
SardiNIA Study
Wellcome Trust Case Control Consortium
FUSION
Liens vers les personnes
Beckmann, Jacques
Vollenweider, Peter
Bergmann, Sven
Bochud, Murielle
Waeber, Gérard
Mooser, Vincent
Liens vers les unités
PTR - Génétique médicale
Service de médecine interne
Médecine sociale et préventive (IUMSP)
ISSN
1546-1718
Statut éditorial
Date de publication
2008
Volume
40
Numéro
6
Première page
768
Dernière page/numéro d’article
775
Peer-reviewed
Langue
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
Sujets
PID Serval
serval:BIB_C6AB1518E478
PMID
Open Access
Date de création
2009-02-20T12:27:33.387Z
Date de création dans IRIS
2025-05-21T01:56:14Z