Association of FTO gene variants with body composition in UK twins

Annals of Human Genetics

Volumn 76, Issue 5, 2012, Pages 333-341

  Livshits, Gregory ^a,b   Malkin, Ida ^b   Moayyeri, Alireza ^a   Spector, Timothy D ^a   Hammond, Christopher J ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b TEL AVIV UNIVERSITY   (Israel)

Author keywords

Association analysis; BMI; Lean and fat body mass; SNP; Waist and hip circumference

Indexed keywords

2 OXOGLUTARIC ACID; FAT MASS AND OBESITY ASSOCIATED PROTEIN; UNCLASSIFIED DRUG;

ADULT; AGE DISTRIBUTION; AGED; ARTICLE; BODY COMPOSITION; BODY FAT; BODY MASS; CHROMOSOME 16Q; CONTROLLED STUDY; FEMALE; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC VARIABILITY; GENOTYPE; HUMAN; LEAN BODY WEIGHT; NORMAL HUMAN; PRIORITY JOURNAL; SAMPLE SIZE; SINGLE NUCLEOTIDE POLYMORPHISM; SOFT TISSUE; TWINS; UNITED KINGDOM; WAIST CIRCUMFERENCE; WAIST HIP RATIO;

ADIPOSE TISSUE; ADULT; AGE FACTORS; AGED; AGED, 80 AND OVER; BODY COMPOSITION; BODY MASS INDEX; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MIDDLE AGED; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEINS; WAIST CIRCUMFERENCE;

EID: 84865102536     PISSN: 00034800     EISSN: 14691809     Source Type: Journal    
DOI: 10.1111/j.1469-1809.2012.00720.x     Document Type: Article

References (36)

1. Anderson, T. W. (1984) An introduction to multivariate statistical analysis (2nd ed.). New York: John Wiley & Sons.
2. Arden N. K. & Spector T. D. (1997) Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J Bone Miner Res 12, 2076-2081.
3. Attaoua, R., Ait El Mkadem, S., Lautier, C., Kaouache, S., Renard, E., Brun J. F., Fedou, C., Gris, J. C., Bringer, J. & Grigorescu, F. (2009) Association of the FTO gene with obesity and the metabolic syndrome is independent of the IRS-2 gene in the female population of Southern France. Diabetes Metab 35, 476-483.
4. Aulchenko, Y. S., Ripke, S., Isaacs, A. & van Duijn, C. M. (2007) GenABEL: An R library for genome-wide association analysis. Bioinformatics 23, 1294-1296.
5. Berulava, T. & Horsthemke, B. (2010) The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels. Eur J Hum Genet 18, 1054-1056.
6. Bogl, L. H., Latvala, A., Kaprio, J., Sovijärvi, O., Rissanen, A. & Pietiläinen, K. H. (2011) An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample. J Bone Miner Res 26, 79-87.
7. Chen, W. M. & Abecasis, G. R. (2007) Family-based association tests for genomewide association scans. Am J Hum Genet 81, 913-926.
8. De Koning, L., Merchant, A. T., Pogue, J. & Anand, S. S. (2007) Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: Meta-regression analysis of prospective studies. Eur Heart J 28, 850-856.
9. Farooqi, I. S. (2011) Genetic, molecular and physiological insights into human obesity. Eur J Clin Invest 41, 451-455.
10. Farooqi, I. S. & O'Rahilly, S. (2006) Genetics of obesity in humans. Endocr Rev 27, 710-718.
11. Fawcett, K. A. & Barroso, I. (2010) The genetics of obesity: FTO leads the way. Trends Genet 2010 26, 266-274.
12. 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. (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894.
13. Gao, X., Shin, Y. H., Li, M., Wang, F., Tong, Q. & Zhang, P. (2010) The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice. PLoS ONE 5(11), e14005.
14. Haupt, A., Thamer, C., Machann, J., Kirchhoff, K., Stefan, N., Tschritter, O., Machicao F, Schick F, Häring HU & Fritsche A. (2008) Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity 2008 16, 1969-1972.
15. Herrera, B. M. & Lindgren, C. M. (2010) The genetics of obesity. Curr Diab Rep 10, 498-505.
16. Hertel, J. K., Johansson, S., Sonestedt, E., Jonsson, A., Lie, R. T., Platou, C. G., Nilsson, P. M., Rukh, G., Midthjell, K., Hveem, K., Melander, O., Groop, L., Lyssenko, V., Molven, A., Orho-Melander, M. & Njølstad, P. R. (2011) FTO, Type 2 diabetes, and weight gain throughout adult life. A meta-analysis of 41, 504 subjects from the scandinavian HUNT, MDC, and MPP Studies. Diabetes 60, 1637-1644.
17. Hinney, A., Nguyen, T. T., Scherag, A., Friedel, S., Brönner, G., Müller, T. D., Grallert, H., Illig, T., Wichmann, HE, Rief, W., Schäfer, H. & Hebebrand, J. (2007) Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PloS ONE 2, e1361.
18. Ho, A. J., Stein, J. L., Hua, X., Lee, S., Hibar, D. P., Leow, A. D., Dinov, I. D., Toga, A. W., Saykin, A. J., Shen, L., Foroud, T., Pankratz, N., Huentelman, M. J., Craig, D. W., Gerber, J. D., Allen, A. N., Corneveaux, J. J., Stephan, D. A., DeCarli, C. S., DeChairo, B. M., Potkin, S. G., Jack, C. R. Jr, Weiner M. W., Raji, C. A., Lopez, O. L., Becker, J. T., Carmichael, O. T. & Thompson, P. M., Alzheimer's Disease Neuroimaging Initiative. (2010) A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly. PNAS 107, 8404-8409.
19. Jacobsson, J. A., Almén, M. A., Benedict, C., Hedberg, L. A., Michaëlsson, K., Brooks, S., Kullberg, J., Axelsson, T., Johansson, L., Ahlström, H., Fredriksson, R., Lind, L. & Schiöth, H. B. (2011) Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly. PLoS ONE 6, e20158.
20. Jacobsson, J. A., Riserus, U., Axelsson, T., Lannfelt, L., Schioth, H. B. & Fredriksson, R., (2009) The common FTO variant rs9939609 is not associated with BMI in a longitudinal study on a cohort of Swedish men born 1920-1924. BMC Med Genet 10, 131.
21. Kaakinen, M., Läärä, E., Pouta, A., Hartikainen, A. L., Laitinen, J., Tammelin, T. H., Herzig, K. H., Sovio, U., Bennett, A. J., Peltonen, L., McCarthy, M. I., Elliott, P., De Stavola, B. & Järvelin, M. R. (2010) Life-course analysis of a fat mass and obesity-associated (FTO) gene variant and body mass index in the Northern Finland Birth Cohort 1966 using structural equation modeling. Am J Epidemiol 2010 172, 653-665.
22. Kilpeläinen, T. O., Zillikens, M. C., Stančákova, A., Finucane, F. M., Ried, J. S., Langenberg, C., Zhang, W., Beckmann, J. S., Luan, J., Vandenput, L., Styrkarsdottir, U., Zhou, Y., Smith, A. V., Zhao, J. H., Amin, N., Vedantam, S., Shin, S. Y., Haritunians, T., Fu, M., Feitosa, M. F., Kumari, M., Halldorsson, B. V., Tikkanen, E., Mangino, M., Hayward, C., Song, C., Arnold, A. M., Aulchenko, Y. S., Oostra, B. A., Campbell, H., Cupples, L. A., Davis, K. E., Döring, A., Eiriksdottir, G., Estrada, K., Fernández-Real, J. M., Garcia, M., Gieger, C., Glazer, N. L., Guiducci, C., Hofman, A., Humphries, S. E., Isomaa, B., Jacobs, L. C., Jula, A., Karasik, D., Karlsson, M. K., Khaw, K. T., Kim, L. J., Kivimäki, M., Klopp, N., Kühnel, B., Kuusisto, J., Liu, Y., Ljunggren, O., Lorentzon, M., Luben, R. N., McKnight, B., Mellström, D., Mitchell, B. D., Mooser, V., Moreno, J. M., Männistö, S., O'Connell, J. R., Pascoe, L., Peltonen, L., Peral, B., Perola, M., Psaty, B. M., Salomaa, V., Savage, D. B., Semple, R. K., Skaric-Juric, T., Sigurdsson, G., Song, K. S., Spector, T. D., Syvänen, A. C., Talmud, P. J., Thorleifsson, G., Thorsteinsdottir, U., Uitterlinden, A. G., van Duijn, C. M., Vidal-Puig, A., Wild, S. H., Wright, A. F., Clegg, D. J., Schadt, E., Wilson, J. F., Rudan, I., Ripatti, S., Borecki, I. B., Shuldiner, A. R., Ingelsson, E., Jansson, J. O., Kaplan, R. C., Gudnason, V., Harris, T. B., Groop, L., Kiel, D. P., Rivadeneira, F., Walker, M., Barroso, I., Vollenweider, P., Waeber, G., Chambers, J. C., Kooner, J. S., Soranzo, N., Hirschhorn, J. N., Stefansson, K., Wichmann, H. E., Ohlsson, C, O'Rahilly, S., Wareham, N. J., Speliotes, E. K., Fox, C. S., Laakso, M. & Loos, R. J. (2011) Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet 43, 753-760.
23. Korostishevsky, M., Cohen, Z., Malkin, I., Ermakov, S., Yarenchuk, O. & Livshits, G. (2010) Morphological and biochemical features of obesity are associated with mineralization genes' polymorphisms. Int J Obes (Lond) 34, 1308-1318.
24. Liem, E. T., Vonk, J. M., Saue, r. P., van der Steege, G., Oosterom, E., Stolk, R. P. & Snieder H. (2010) Influence of common variants near INSIG2, in FTO, and near MC4R genes on overweight and the metabolic profile in adolescence: The TRAILS (TRacking Adolescents' Individual Lives Survey) Study. Am J Clin Nutr 91, 321-328.
25. Livshits, G., Kato, B. S., Wilson, S. G. & Spector, T. D. (2007) Linkage of genes to total lean body mass in normal women. J Clin Endocrinol Metab 98, 371-376.
26. Livshits, G., Yakovenko, K., Ginsburg, E. & Kobyliansky, E. (1998) Genetics of human body size and shape: Pleiotropic and independent genetic determinants of adiposity. Ann Hum Biol 25, 221-236.
27. Lopez-Bermejo, A., Petry, C. J., Diaz, M., Sebastiani, G., de Zegher, F., Dunger, D. B. & Ibáñez L. (2008) The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. J Clin Endocrinal Metab 93, 1501-1505.
28. Malkin, I. & Ginsburg, E. (2009) Program package for Mendelian analysis of pedigree data (MAN, Version 9);Technical Report. Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University.
29. Mangge, H., Renner, W., Almer, G., Weghuber, D., Möller, R. & Horejsi, R. (2011) Rs9939609 variant of the fat mass and obesity-associated gene and trunk obesity in adolescents. J Obesity 2011, 186368.
30. Rutters, F., Nieuwenhuizen, A. G., Bouwman, F., Mariman, E. & Westerterp-Plantenga, M. S. (2011) Associations between a single nucleotide polymorphism of the FTO Gene (rs9939609) and obesity-related characteristics over time during puberty in a Dutch children cohort. J Clin Endocrinal Metab 96, E939-E942.
31. Sanchez-Pulido L. & Andrade-Navarro MA. (2007) The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily. BMC Biochem 8(23), 1-6.
32. Scuteri, A., Sanna, S., Chen, W. M., Uda, M., Albai, G., Strait, J., Najjar, S., Nagaraja, R., Orrú, 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. (2007) Genome-wide association scan shows genetic variants in the FTO Gene are associated with obesity-related traits. PloS Genet 3, e115.
33. Sonestedt, E., Gullberg, B., Ericson, U., Wirfält, E., Hedblad, B. & Orho-Melander, M. (2011) Association between fat intake, physical activity and mortality depending on genetic variation in FTO. Int J Obes (Lond) 35, 1041-1049.
34. Southam, L., Panoutsopoulou, K., Rayner, N. W., Chapman, K., Durrant, C., Ferreira, T., Arden, N., Carr, A., Deloukas, P., Doherty, M., Loughlin, J., McCaskie, A., Ollier, W. E., Ralston, S., Spectorm, T. D., Valdes, A. M., Wallis, G. A., Wilkinson J. M.; arcOGEN consortium, Marchini, J. & Zeggini, E. (2011) The effect of genome-wide association scan quality control on imputation outcome for common variants. Eur J Hum Genet 19, 610-614.
35. Spector, T. D. & Williams, F. M. (2006) The UK Adult Twin Registry (TwinsUK). Twin Res Hum Genet 9, 899-906.
36. Xi, B., Shen, Y., Zhang, M., Liu, X., Zhao, X., Wu, L., Cheng, H., Hou, D., Lindpaintner, K., Liu, L., Mi, J. & Wang, X. (2010) The common rs9939609 variant of the fat mass and obesity-associated gene is associated with obesity risk in children and adolescents of Beijing, China. BMC Med Genet 11, 107.