Association study of MC4R with complex obesity and replication of the rs17782313 association signal

Molecular Genetics and Metabolism

Volumn 103, Issue 1, 2011, Pages 71-75

  Beckers, Sigri ^a   Zegers, Doreen ^a   de Freitas, Fenna ^a   Mertens, Ilse L ^b   Van Gaal, Luc F ^b   Van Hul, Wim ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

^b ANTWERP UNIVERSITY HOSPITAL   (Belgium)

Author keywords

Association; Melanocortin 4 receptor; Obesity

Indexed keywords

MELANOCORTIN 4 RECEPTOR;

ADULT; ARTICLE; BODY MASS; BODY WEIGHT; CONTROLLED STUDY; FEMALE; GENOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; OBESITY; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; ALLELES; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; MALE; MIDDLE AGED; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTOR, MELANOCORTIN, TYPE 4; RISK FACTORS;

EID: 79955138611     PISSN: 10967192     EISSN: 10967206     Source Type: Journal    
DOI: 10.1016/j.ymgme.2011.01.007     Document Type: Article

References (25)

1. Frayling T.M., Timpson N.J., Weedon M.N., Zeggini E., Freathy R.M., Lindgren C.M., Perry J.R., Elliott K.S., Lango H., Rayner N.W., Shields B., Harries L.W., Barrett J.C., Ellard S., Groves C.J., Knight B., Patch A.M., Ness A.R., Ebrahim S., Lawlor D.A., Ring S.M., Ben-Shlomo Y., Jarvelin M.R., Sovio U., Bennett A.J., Melzer D., Ferrucci L., Loos R.J., Barroso I., Wareham N.J., Karpe F., Owen K.R., Cardon L.R., Walker M., Hitman G.A., Palmer C.N., Doney A.S., Morris A.D., Smith G.D., Hattersley A.T., McCarthy M.I. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007, 316:889-894.
2. Dina C., Meyre D., Gallina S., Durand E., Korner A., Jacobson P., Carlsson L.M., Kiess W., Vatin V., Lecoeur C., Delplanque J., Vaillant E., Pattou F., Ruiz J., Weill J., Levy-Marchal C., Horber F., Potoczna N., Hercberg S., Le Stunff C., Bougneres P., Kovacs P., Marre M., Balkau B., Cauchi S., Chevre J.C., Froguel P. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat. Genet. 2007, 39:724-726.
3. Scuteri A., Sanna S., Chen W.M., Uda M., Albai G., Strait J., Najjar S., Nagaraja R., Orru M., Usala G., Dei M., Lai S., Maschio A., Busonero F., Mulas A., Ehret G.B., Fink A.A., Weder A.B., Cooper R.S., Galan P., Chakravarti A., Schlessinger D., Cao A., Lakatta E., Abecasis G.R. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007, 3:e115.
4. Peeters A., Beckers S., Verrijken A., Roevens P., Peeters P., Van Gaal L., Van Hul W. Variants in the FTO gene are associated with common obesity in the Belgian population. Mol. Genet. Metab. 2008, 93:481-484.
5. 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., 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., 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., Rayner N.W., Ring S.M., Sandhu M.S., Scherag A., Sims M.A., Song K., Soranzo N., Speliotes E.K., Syddall H.E., Teichmann S.A., Timpson N.J., Tobias J.H., Uda M., Vogel C.I., Wallace C., Waterworth D.M., Weedon M.N., Willer C.J., Wraight, 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., 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. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 2008, 40:768-775.
6. Larsen L.H., Echwald S.M., Sorensen T.I., Andersen T., Wulff B.S., Pedersen O. Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. J. Clin. Endocrinol. Metab. 2005, 90:219-224.
7. Lubrano-Berthelier C., Dubern B., Lacorte J.M., Picard F., Shapiro A., Zhang S., Bertrais S., Hercberg S., Basdevant A., Clement K., Vaisse C. Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating. J. Clin. Endocrinol. Metab. 2006, 91:1811-1818.
8. Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988, 16:1215.
9. de Bakker P.I., Yelensky R., Pe'er I., Gabriel S.B., Daly M.J., Altshuler D. Efficiency and power in genetic association studies. Nat. Genet. 2005, 37:1217-1223.
10. Ott J. Documentation to LINKAGE UTILITY Programs accessed on 15 May 2010. http://linkage.rockefeller.edu/ott/linkutil.htm.
11. Gauderman W.J., Morrison J.M. QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies accessed on 15 May 2010. http://hydra.usc.edu/gxe.
12. Benjamini Y., Hochberg Y. Controlling the false discovery rate-a practical and powerful approach to multiple testing. J. R. Stat. Soc. B Methodol. 1995, 57:289-300.
13. Willer C.J., Speliotes E.K., Loos R.J., Li S., Lindgren C.M., Heid I.M., Berndt S.I., Elliott A.L., Jackson A.U., Lamina C., Lettre G., Lim N., Lyon H.N., McCarroll S.A., Papadakis K., Qi L., Randall J.C., Roccasecca R.M., Sanna S., Scheet P., Weedon M.N., Wheeler E., Zhao J.H., Jacobs L.C., Prokopenko I., Soranzo N., Tanaka T., Timpson N.J., Almgren P., Bennett A., Bergman R.N., Bingham S.A., Bonnycastle L.L., Brown M., Burtt N.P., Chines P., Coin L., Collins F.S., Connell J.M., Cooper C., Smith G.D., Dennison E.M., Deodhar P., Elliott P., Erdos M.R., Estrada K., Evans D.M., Gianniny L., Gieger C., Gillson C.J., Guiducci C., Hackett R., Hadley D., Hall A.S., Havulinna A.S., Hebebrand J., Hofman A., Isomaa B., Jacobs K.B., Johnson T., Jousilahti P., Jovanovic Z., Khaw K.T., Kraft P., Kuokkanen M., Kuusisto J., Laitinen J., Lakatta E.G., Luan J., Luben R.N., Mangino M., McArdle W.L., Meitinger T., Mulas A., Munroe P.B., Narisu N., Ness A.R., Northstone K., O'Rahilly S., Purmann C., Rees M.G., Ridderstrale M., Ring S.M., Rivadeneira F., Ruokonen A., Sandhu M.S., Saramies J., Scott L.J., Scuteri A., Silander K., Sims M.A., Song K., Stephens J., Stevens S., Stringham H.M., Tung Y.C., Valle T.T., Van Duijn C.M., Vimaleswaran K.S., Vollenweider P., Waeber G., Wallace C., Watanabe R.M., Waterworth D.M., Watkins N., Witteman J.C., Zeggini E., Zhai G., Zillikens M.C., Altshuler D., Caulfield M.J., Chanock S.J., Farooqi I.S., Ferrucci L., Guralnik J.M., Hattersley A.T., Hu F.B., Jarvelin M.R., Laakso M., Mooser V., Ong K.K., Ouwehand W.H., Salomaa V., Samani N.J., Spector T.D., Tuomi T., Tuomilehto J., Uda M., Uitterlinden A.G., Wareham N.J., Deloukas P., Frayling T.M., Groop L.C., Hayes R.B., Hunter D.J., Mohlke K.L., Peltonen L., Schlessinger D., Strachan D.P., Wichmann H.E., McCarthy M.I., Boehnke M., Barroso I., Abecasis G.R., Hirschhorn J.N. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 2009, 41:25-34.
14. Thorleifsson G., Walters G.B., Gudbjartsson D.F., Steinthorsdottir V., Sulem P., Helgadottir A., Styrkarsdottir U., Gretarsdottir S., Thorlacius S., Jonsdottir I., Jonsdottir T., Olafsdottir E.J., Olafsdottir G.H., Jonsson T., Jonsson F., Borch-Johnsen K., Hansen T., Andersen G., Jorgensen T., Lauritzen T., Aben K.K., Verbeek A.L., Roeleveld N., Kampman E., Yanek L.R., Becker L.C., Tryggvadottir L., Rafnar T., Becker D.M., Gulcher J., Kiemeney L.A., Pedersen O., Kong A., Thorsteinsdottir U., Stefansson K. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. 2009, 41:18-24.
15. Meyre D., Delplanque J., Chevre J.C., Lecoeur C., Lobbens S., Gallina S., Durand E., Vatin V., Degraeve F., Proenca C., Gaget S., Korner A., Kovacs P., Kiess W., Tichet J., Marre M., Hartikainen A.L., Horber F., Potoczna N., Hercberg S., Levy-Marchal C., Pattou F., Heude B., Tauber M., McCarthy M.I., Blakemore A.I., Montpetit A., Polychronakos C., Weill J., Coin L.J., Asher J., Elliott P., Jarvelin M.R., Visvikis-Siest S., Balkau B., Sladek R., Balding D., Walley A., Dina C., Froguel P. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat. Genet. 2009, 41:157-159.
16. Heard-Costa N.L., Zillikens M.C., Monda K.L., Johansson A., Harris T.B., Fu M., Haritunians T., Feitosa M.F., Aspelund T., Eiriksdottir G., Garcia M., Launer L.J., Smith A.V., Mitchell B.D., McArdle P.F., Shuldiner A.R., Bielinski S.J., Boerwinkle E., Brancati F., Demerath E.W., Pankow J.S., Arnold A.M., Chen Y.D., Glazer N.L., McKnight B., Psaty B.M., Rotter J.I., Amin N., Campbell H., Gyllensten U., Pattaro C., Pramstaller P.P., Rudan I., Struchalin M., Vitart V., Gao X., Kraja A., Province M.A., Zhang Q., Atwood L.D., Dupuis J., Hirschhorn J.N., Jaquish C.E., O'Donnell C.J., Vasan R.S., White C.C., Aulchenko Y.S., Estrada K., Hofman A., Rivadeneira F., Uitterlinden A.G., Witteman J.C., Oostra B.A., Kaplan R.C., Gudnason V., O'Connell J.R., Borecki I.B., van Duijn C.M., Cupples L.A., Fox C.S., North K.E. NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS Genet. 2009, 5:e1000539.
17. Lindgren C.M., Heid I.M., Randall J.C., Lamina C., Steinthorsdottir V., Qi L., Speliotes E.K., Thorleifsson G., Willer C.J., Herrera B.M., Jackson A.U., Lim N., Scheet P., Soranzo N., Amin N., Aulchenko Y.S., Chambers J.C., Drong A., Luan J., Lyon H.N., Rivadeneira F., Sanna S., Timpson N.J., Zillikens M.C., Zhao J.H., Almgren P., Bandinelli S., Bennett A.J., Bergman R.N., Bonnycastle L.L., Bumpstead S.J., Chanock S.J., Cherkas L., Chines P., Coin L., Cooper C., Crawford G., Doering A., Dominiczak A., Doney A.S., Ebrahim S., Elliott P., Erdos M.R., Estrada K., Ferrucci L., Fischer G., Forouhi N.G., Gieger C., Grallert H., Groves C.J., Grundy S., Guiducci C., Hadley D., Hamsten A., Havulinna A.S., Hofman A., Holle R., Holloway J.W., Illig T., Isomaa B., Jacobs L.C., Jameson K., Jousilahti P., Karpe F., Kuusisto J., Laitinen J., Lathrop G.M., Lawlor D.A., Mangino M., McArdle W.L., Meitinger T., Morken M.A., Morris A.P., Munroe P., Narisu N., Nordstrom A., Nordstrom P., Oostra B.A., Palmer C.N., Payne F., Peden J.F., Prokopenko I., Renstrom F., Ruokonen A., Salomaa V., Sandhu M.S., Scott L.J., Scuteri A., Silander K., Song K., Yuan X., Stringham H.M., Swift A.J., Tuomi T., Uda M., Vollenweider P., Waeber G., Wallace C., Walters G.B., Weedon M.N., Witteman J.C., Zhang C., Zhang W., Caulfield M.J., Collins F.S., Davey Smith G., Day I.N., Franks P.W., Hattersley A.T., Hu F.B., Jarvelin M.R., Kong A., Kooner J.S., Laakso M., Lakatta E., Mooser V., Morris A.D., Peltonen L., Samani N.J., Spector T.D., Strachan D.P., Tanaka T., Tuomilehto J., Uitterlinden A.G., van Duijn C.M., Wareham N.J., Hugh W., Waterworth D.M., Boehnke M., Deloukas P., Groop L., Hunter D.J., Thorsteinsdottir U., Schlessinger D., Wichmann H.E., Frayling T.M., Abecasis G.R., Hirschhorn J.N., Loos R.J., Stefansson K., Mohlke K.L., Barroso I., McCarthy M.I. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution. PLoS Genet. 2009, 5:e1000508.
18. Loos R.J., Bouchard C. FTO: the first gene contributing to common forms of human obesity. Obes. Rev. 2008, 9:246-250.
19. Zobel D.P., Andreasen C.H., Grarup N., Eiberg H., Sorensen T.I., Sandbaek A., Lauritzen T., Borch-Johnsen K., Jorgensen T., Pedersen O., Hansen T. Variants near MC4R are associated with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14, 940 Danes. Diabetes 2009, 58:757-764.
20. Renstrom F., Payne F., Nordstrom A., Brito E.C., Rolandsson O., Hallmans G., Barroso I., Nordstrom P., Franks P.W. Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum. Mol. Genet. 2009, 18:1489-1496.
21. Tenesa A., Campbell H., Theodoratou E., Dunlop L., Cetnarskyj R., Farrington S.M., Dunlop M.G. Common genetic variants at the MC4R locus are associated with obesity, but not with dietary energy intake or colorectal cancer in the Scottish population. Int. J. Obes. (Lond.) 2009, 33:284-288.
22. Heid I.M., Vollmert C., Hinney A., Doring A., Geller F., Lowel H., Wichmann H.E., Illig T., Hebebrand J., Kronenberg F. Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys. J. Med. Genet. 2005, 42:e21.
23. Stutzmann F., Vatin V., Cauchi S., Morandi A., Jouret B., Landt O., Tounian P., Levy-Marchal C., Buzzetti R., Pinelli L., Balkau B., Horber F., Bougneres P., Froguel P., Meyre D. Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene. Hum. Mol. Genet. 2007, 16:1837-1844.
24. Geller F., Reichwald K., Dempfle A., Illig T., Vollmert C., Herpertz S., Siffert W., Platzer M., Hess C., Gudermann T., Biebermann H., Wichmann H.E., Schafer H., Hinney A., Hebebrand J. Melanocortin-4 receptor gene variant I103 is negatively associated with obesity. Am. J. Hum. Genet. 2004, 74:572-581.
25. Young E.H., Wareham N.J., Farooqi S., Hinney A., Hebebrand J., Scherag A., O'Rahilly S., Barroso I., Sandhu M.S. The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals. Int. J. Obes. (Lond.) 2007, 31:1437-1441.