Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity

Nature Genetics - Tập 41 Số 1 - Trang 18-24 - 2009
Guðmar Þorleifsson1, G. Bragi Walters1, Daníel F. Guðbjartsson1, Valgerður Steinthórsdóttir1, Patrick Sulem1, Anna Helgadóttir1, Unnur Styrkársdóttir1, Sólveig Grétarsdóttir1, Steinunn Thorlacius1, Ingileif Jónsdóttir2,1, Þorbjörg Jónsdóttir1, Elínborg J. Ólafsdóttir3, Guðríður H. Ólafsdóttir3, Þorvaldur Jónsson4,2, Frosti Jónsson1, Knut Borch‐Johnsen5,6, Torben Hansen6, Gary L. Andersen6, Torben Jørgensen7,8, Torsten Lauritzen9, Katja K.H. Aben10, André L. M. Verbeek11, Nel Roeleveld11, Ellen Kampman11, Lisa R. Yanek12, Lewis C. Becker12, Laufey Tryggvadóttír3, Þórunn Rafnar1, Diane M. Becker12, Jeffrey R. Gulcher1, Lambertus A. Kiemeney10,13,11, Oluf Pedersen5,7,6, Augustine Kong1, Unnur Þorsteinsdóttir2,1, Kāri Stefánsson2,1
1deCODE Genetics, Reykjavik, Iceland
2Faculty of Medicine, University of Iceland, Reykjavík, Iceland
3Icelandic Cancer Registry, Reykjavik, Iceland
4Department of Surgery, University Hospital, Reykjavik, Iceland
5Faculty of Health Science, University of Aarhus, Aarhus, Denmark
6Steno Diabetes Center, Copenhagen, Denmark
7Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
8Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
9The Department of General Medical Practice, University of Aarhus, Aarhus, Denmark
10Comprehensive Cancer Centre East, Nijmegen, The Netherlands
11Radboud University Nijmegen Medical Center Department of Epidemiology & Biostatistics, Nijmegen, The Netherlands
12The Johns Hopkins Sibling and Family Heart Study, The Johns Hopkins University School of Medicine, Baltimore, USA
13Radboud University Nijmegen Department of Urology, Nijmegen, The Netherlands

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Parikh, N.I. et al. Increasing trends in incidence of overweight and obesity over 5 decades. Am. J. Med. 120, 242–250 (2007).

Ogden, C.L. et al. Prevalence of overweight and obesity in the United States, 1999–2004. J. Am. Med. Assoc. 295, 1549–1555 (2006).

Haslam, D.W. & James, W.P. Obesity. Lancet 366, 1197–1209 (2005).

Wardle, J., Carnell, S., Haworth, C.M. & Plomin, R. Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment. Am. J. Clin. Nutr. 87, 398–404 (2008).

Maes, H.H., Neale, M.C. & Eaves, L.J. Genetic and environmental factors in relative body weight and human adiposity. Behav. Genet. 27, 325–351 (1997).

Rankinen, T. et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 14, 529–644 (2006).

Mutch, D.M. & Clement, K. Unraveling the genetics of human obesity. PLoS Genet. 2, e188 (2006).

Gudbjartsson, D.F. et al. Many sequence variants affecting diversity of adult human height. Nat. Genet. 40, 609–615 (2008).

Frayling, T.M. et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889–894 (2007).

Loos, R.J. et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 40, 768–775 (2008).

Chambers, J.C. et al. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat. Genet. 40, 716–718 (2008).

Saxena, R. et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 1331–1336 (2007).

International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).

Willer, C.J. et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. advance online publication, doi:10.1038/ng.287 (14 December 2008).

Jurvansuu, J. et al. Transmembrane protein 18 enhances the tropism of neural stem cells for glioma cells. Cancer Res. 68, 4614–4622 (2008).

Jamshidi, Y., Snieder, H., Ge, D., Spector, T.D. & O'Dell, S.D. The SH2B gene is associated with serum leptin and body fat in normal female twins. Obesity (Silver Spring) 15, 5–9 (2007).

Chouchane, L. et al. Genetic variation in the stress protein hsp70–2 gene is highly associated with obesity. Int. J. Obes. Relat. Metab. Disord. 25, 462–466 (2001).

Hamid, Y.H. et al. The common T60N polymorphism of the lymphotoxin-alpha gene is associated with type 2 diabetes and other phenotypes of the metabolic syndrome. Diabetologia 48, 445–451 (2005).

Sookoian, S.C., Gonzalez, C. & Pirola, C.J. Meta-analysis on the G-308A tumor necrosis factor alpha gene variant and phenotypes associated with the metabolic syndrome. Obes. Res. 13, 2122–2131 (2005).

Willer, C.J. et al. Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes. Diabetes 56, 256–264 (2007).

Gratacos, M. et al. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol. Psychiatry 61, 911–922 (2007).

Gunstad, J. et al. BDNF Val66Met polymorphism is associated with body mass index in healthy adults. Neuropsychobiology 53, 153–156 (2006).

Aravind, L. & Koonin, E.V. Fold prediction and evolutionary analysis of the POZ domain: structural and evolutionary relationship with the potassium channel tetramerization domain. J. Mol. Biol. 285, 1353–1361 (1999).

Ding, X.F. et al. Characterization and expression of a human KCTD1 gene containing the BTB domain, which mediates transcriptional repression and homomeric interactions. DNA Cell Biol. 27, 257–265 (2008).

Marg, A. et al. Neurotractin, a novel neurite outgrowth-promoting Ig-like protein that interacts with CEPU-1 and LAMP. J. Cell Biol. 145, 865–876 (1999).

Schafer, M., Brauer, A.U., Savaskan, N.E., Rathjen, F.G. & Brummendorf, T. Neurotractin/kilon promotes neurite outgrowth and is expressed on reactive astrocytes after entorhinal cortex lesion. Mol. Cell. Neurosci. 29, 580–590 (2005).

Mi, H. et al. The PANTHER database of protein families, subfamilies, functions and pathways. Nucleic Acids Res. 33, D284–D288 (2005).

Gullicksen, P.S., Della-Fera, M.A. & Baile, C.A. Leptin-induced adipose apoptosis: Implications for body weight regulation. Apoptosis 8, 327–335 (2003).

Emilsson, V. et al. Genetics of gene expression and its effect on disease. Nature 452, 423–428 (2008).

Steinthorsdottir, V. et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat. Genet. 39, 770–775 (2007).

Gulcher, J.R., Kristjansson, K., Gudbjartsson, H. & Stefansson, K. Protection of privacy by third-party encryption in genetic research in Iceland. Eur. J. Hum. Genet. 8, 739–742 (2000).

Jorgensen, T. et al. A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur. J. Cardiovasc. Prev. Rehabil. 10, 377–386 (2003).

Lauritzen, T. et al. The ADDITION study: proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with Type 2 diabetes detected by screening. Int. J. Obes. Relat. Metab. Disord. 24, Suppl 3, S6–S11 (2000).

Kutyavin, I.V. et al. A novel endonuclease IV post-PCR genotyping system. Nucleic Acids Res. 34, e128 (2006).

Devlin, B., Bacanu, S.A. & Roeder, K. Genomic Control to the extreme. Nat. Genet. 36, 1129–1130 (2004).