Tags

Type your tag names separated by a space and hit enter

Common variants near MC4R are associated with fat mass, weight and risk of obesity.
Nat Genet 2008; 40(6):768-75NGen

Abstract

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.

Authors+Show Affiliations

MRC Epidemiology Unit, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18454148

Citation

Loos, Ruth J F., et al. "Common Variants Near MC4R Are Associated With Fat Mass, Weight and Risk of Obesity." Nature Genetics, vol. 40, no. 6, 2008, pp. 768-75.
Loos RJ, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008;40(6):768-75.
Loos, R. J., Lindgren, C. M., Li, S., Wheeler, E., Zhao, J. H., Prokopenko, I., ... Mohlke, K. L. (2008). Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature Genetics, 40(6), pp. 768-75. doi:10.1038/ng.140.
Loos RJ, et al. Common Variants Near MC4R Are Associated With Fat Mass, Weight and Risk of Obesity. Nat Genet. 2008;40(6):768-75. PubMed PMID: 18454148.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Common variants near MC4R are associated with fat mass, weight and risk of obesity. AU - Loos,Ruth J F, AU - Lindgren,Cecilia M, AU - Li,Shengxu, AU - Wheeler,Eleanor, AU - Zhao,Jing Hua, AU - Prokopenko,Inga, AU - Inouye,Michael, AU - Freathy,Rachel M, AU - Attwood,Antony P, AU - Beckmann,Jacques S, AU - Berndt,Sonja I, AU - ,, AU - Jacobs,Kevin B, AU - Chanock,Stephen J, AU - Hayes,Richard B, AU - Bergmann,Sven, AU - Bennett,Amanda J, AU - Bingham,Sheila A, AU - Bochud,Murielle, AU - Brown,Morris, AU - Cauchi,Stéphane, AU - Connell,John M, AU - Cooper,Cyrus, AU - Smith,George Davey, AU - Day,Ian, AU - Dina,Christian, AU - De,Subhajyoti, AU - Dermitzakis,Emmanouil T, AU - Doney,Alex S F, AU - Elliott,Katherine S, AU - Elliott,Paul, AU - Evans,David M, AU - Sadaf Farooqi,I, AU - Froguel,Philippe, AU - Ghori,Jilur, AU - Groves,Christopher J, AU - Gwilliam,Rhian, AU - Hadley,David, AU - Hall,Alistair S, AU - Hattersley,Andrew T, AU - Hebebrand,Johannes, AU - Heid,Iris M, AU - ,, AU - Lamina,Claudia, AU - Gieger,Christian, AU - Illig,Thomas, AU - Meitinger,Thomas, AU - Wichmann,H-Erich, AU - Herrera,Blanca, AU - Hinney,Anke, AU - Hunt,Sarah E, AU - Jarvelin,Marjo-Riitta, AU - Johnson,Toby, AU - Jolley,Jennifer D M, AU - Karpe,Fredrik, AU - Keniry,Andrew, AU - Khaw,Kay-Tee, AU - Luben,Robert N, AU - Mangino,Massimo, AU - Marchini,Jonathan, AU - McArdle,Wendy L, AU - McGinnis,Ralph, AU - Meyre,David, AU - Munroe,Patricia B, AU - Morris,Andrew D, AU - Ness,Andrew R, AU - Neville,Matthew J, AU - Nica,Alexandra C, AU - Ong,Ken K, AU - O'Rahilly,Stephen, AU - Owen,Katharine R, AU - Palmer,Colin N A, AU - Papadakis,Konstantinos, AU - Potter,Simon, AU - Pouta,Anneli, AU - Qi,Lu, AU - ,, AU - Randall,Joshua C, AU - Rayner,Nigel W, AU - Ring,Susan M, AU - Sandhu,Manjinder S, AU - Scherag,André, AU - Sims,Matthew A, AU - Song,Kijoung, AU - Soranzo,Nicole, AU - Speliotes,Elizabeth K, AU - ,, AU - Syddall,Holly E, AU - Teichmann,Sarah A, AU - Timpson,Nicholas J, AU - Tobias,Jonathan H, AU - Uda,Manuela, AU - ,, AU - Vogel,Carla I Ganz, AU - Wallace,Chris, AU - Waterworth,Dawn M, AU - Weedon,Michael N, AU - ,, AU - Willer,Cristen J, AU - ,, AU - Wraight,, AU - Yuan,Xin, AU - Zeggini,Eleftheria, AU - Hirschhorn,Joel N, AU - Strachan,David P, AU - Ouwehand,Willem H, AU - Caulfield,Mark J, AU - Samani,Nilesh J, AU - Frayling,Timothy M, AU - Vollenweider,Peter, AU - Waeber,Gerard, AU - Mooser,Vincent, AU - Deloukas,Panos, AU - McCarthy,Mark I, AU - Wareham,Nicholas J, AU - Barroso,Inês, AU - Jacobs,Kevin B, AU - Chanock,Stephen J, AU - Hayes,Richard B, AU - Lamina,Claudia, AU - Gieger,Christian, AU - Illig,Thomas, AU - Meitinger,Thomas, AU - Wichmann,H-Erich, AU - Kraft,Peter, AU - Hankinson,Susan E, AU - Hunter,David J, AU - Hu,Frank B, AU - Lyon,Helen N, AU - Voight,Benjamin F, AU - Ridderstrale,Martin, AU - Groop,Leif, AU - Scheet,Paul, AU - Sanna,Serena, AU - Abecasis,Goncalo R, AU - Albai,Giuseppe, AU - Nagaraja,Ramaiah, AU - Schlessinger,David, AU - Jackson,Anne U, AU - Tuomilehto,Jaakko, AU - Collins,Francis S, AU - Boehnke,Michael, AU - Mohlke,Karen L, Y1 - 2008/05/04/ PY - 2007/11/16/received PY - 2008/02/19/accepted PY - 2008/5/6/pubmed PY - 2008/6/20/medline PY - 2008/5/6/entrez SP - 768 EP - 75 JF - Nature genetics JO - Nat. Genet. VL - 40 IS - 6 N2 - 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. SN - 1546-1718 UR - https://www.unboundmedicine.com/medline/citation/18454148/Common_variants_near_MC4R_are_associated_with_fat_mass_weight_and_risk_of_obesity_ L2 - http://dx.doi.org/10.1038/ng.140 DB - PRIME DP - Unbound Medicine ER -