Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile

Nature Genetics

Volumn 43, Issue 8, 2011, Pages 753-760

  Kilpeläinen, Tuomas O ^a   Zillikens, M Carola ^b,c   Stančákova, Alena ^d   Finucane, Francis M ^a   Ried, Janina S ^e   Langenberg, Claudia ^a   Zhang, Weihua ^f   Beckmann, Jacques S ^g   Luan, Jian'An ^a   Vandenput, Liesbeth ^h   Styrkarsdottir, Unnur ⁱ   Zhou, Yanhua ^j   Smith, Albert Vernon ^k   Zhao, Jing Hua ^a   Amin, Najaf ^b   Vedantam, Sailaja ^l,m   Shin, So Youn ⁿ   Haritunians, Talin ^o   Fu, Mao ^p   Feitosa, Mary F ^q   Kumari, Meena ^r   Halldorsson, Bjarni V ^i,s   Tikkanen, Emmi ^t,u   Mangino, Massimo ^v   Hayward, Caroline ^w   Song, Ci ^x   Arnold, Alice M ^y   Aulchenko, Yurii S ^b   Oostra, Ben A ^b   Campbell, Harry ^z   Cupples, L Adrienne ^j,aa   Davis, Kathryn E ^ab   Döring, Angela ^e   Eiriksdottir, Gudny ^k   Estrada, Karol ^b,c   Fernández Real, José Manuel ^ac   Garcia, Melissa ^ad   Gieger, Christian ^e   Glazer, Nicole L ^y,ae   Guiducci, Candace ^l   Hofman, Albert ^b,c   Humphries, Steve E ^r   Isomaa, Bo ^af,ag   Jacobs, Leonie C ^b   Jula, Antti ^u   Karasik, David ^ah   Karlsson, Magnus K ^ai,aj   Khaw, Kay Tee ^ak   Kim, Lauren J ^ad   Kivimäki, Mika ^r   Klopp, Norman ^e   Kühnel, Brigitte ^y   Kuusisto, Johanna ^d   Liu, Yongmei ^al   Ljunggren, Östen ^am   Lorentzon, Mattias ^h   Luben, Robert N ^ak   McKnight, Barbara ^y,ae   Mellström, Dan ^h   Mitchell, Braxton D ^p   Mooser, Vincent ^an   Moreno, José Maria ^ac   Männistö, Satu ^u   O'Connell, Jeffery R ^p   Pascoe, Laura ^ao   Peltonen, Leena ^n,t,u   Peral, Belén ^y,ap   Perola, Markus ^t,u   Psaty, Bruce M ^d,i,y,ae,aq   Salomaa, Veikko ^u   Savage, David B ^ar   Semple, Robert K ^ar   Skaric Juric, Tatjana ^as   Sigurdsson, Gunnar ^at,au   Song, Kijoung S ^an   Spector, Timothy D ^v   Syvänen, Ann Christine ^am   Talmud, Philippa J ^r   Thorleifsson, Gudmar ⁱ   Thorsteinsdottir, Unnur ^i,au   Uitterlinden, Andrá G ^b,c   Van Duijn, Cornelia M ^b,c,av   Vidal Puig, Antonio ^ar   Wild, Sarah H ^z   Wright, Alan F ^w   Clegg, Deborah J ^ab   Schadt, Eric ^aw,ax   Wilson, James F ^z   Rudan, Igor ^z,ay,az   Ripatti, Samuli ^t,u   Borecki, Ingrid B ^q   Shuldiner, Alan R ^p,ba   Ingelsson, Erik ^x,bb   Jansson, John Olov ^h   Kaplan, Robert C ^bc   Gudnason, Vilmundur ^k,au   Harris, Tamara B ^ad   Groop, Leif ^bd   Kiel, Douglas P ^ah   Rivadeneira, Fernando ^b,c   Walker, Mark ^ao   Barroso, Inês ^n,ar   Vollenweider, Peter ^g   Waeber, Gérard ^g   Chambers, John C ^f   Kooner, Jaspal S ^be   Soranzo, Nicole ⁿ   Hirschhorn, Joel N ^l,m,ah   Stefansson, Kari ^i,au   Wichmann, H Erich ^e,bf   Ohlsson, Claes ^h   O'Rahilly, Stephen ^ar   Wareham, Nicholas J ^a   Speliotes, Elizabeth K ^l,bg   Fox, Caroline S ^ah   Laakso, Markku ^d   Loos, Ruth J F ^a   more..

^a INSTITUTE OF METABOLIC SCIENCE   (United Kingdom)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c Netherlands Genomics Initiative   (Netherlands)

^d KUOPIO UNIVERSITY HOSPITAL   (Finland)

^e INSTITUTE OF EPIDEMIOLOGY   (Germany)

^f IMPERIAL COLLEGE LONDON   (United Kingdom)

^g LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^h UNIVERSITY OF GOTHENBURG   (Sweden)

ⁱ DECODE GENETICS   (Iceland)

^j BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

^k ICELANDIC HEART ASSOCIATION   (Iceland)

^l BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^m BOSTON CHILDREN S HOSPITAL   (United States)

ⁿ WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^o CEDARS SINAI MEDICAL CENTER   (United States)

^p UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^q WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^r UNIVERSITY COLLEGE LONDON   (United Kingdom)

^s REYKJAVIK UNIVERSITY   (Iceland)

^t UNIVERSITY OF HELSINKI   (Finland)

^u NATIONAL PUBLIC HEALTH INSTITUTE   (Finland)

^v KING'S COLLEGE LONDON   (United Kingdom)

^w UNIVERSITY OF EDINBURGH   (United Kingdom)

^x KAROLINSKA INSTITUTE   (Sweden)

^y UNIVERSITY OF WASHINGTON   (United States)

^z UNIVERSITY OF EDINBURGH   (United Kingdom)

^aa FRAMINGHAM HEART STUDY   (United States)

^ab UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^ac Instituto de Salud Carlos III   (Spain)

^ad NATIONAL INSTITUTE ON AGING   (United States)

^ae UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^af FOLKHÄLSAN RESEARCH CENTER   (Finland)

^ag Hebrew SeniorLife and Harvard Medical School ^*  (Finland)

^ah HARVARD MEDICAL SCHOOL   (United States)

^ai LUND UNIVERSITY   (Sweden)

^aj LUND UNIVERSITY HOSPITAL   (Sweden)

^ak UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^al WAKE FOREST SCHOOL OF MEDICINE   (United States)

^am UPPSALA UNIVERSITY   (Sweden)

^an GLAXOSMITHKLINE   (United States)

^ao NEWCASTLE UNIVERSITY   (United Kingdom)

^ap UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^aq CENTER FOR HEALTH STUDIES   (United States)

^ar UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^as INSTITUTE FOR ANTHROPOLOGICAL RESEARCH   (Croatia)

^at LANDSPITALI UNIVERSITY HOSPITAL   (Iceland)

^au UNIVERSITY OF ICELAND   (Iceland)

^av LEIDEN UNIVERSITY   (Netherlands)

^aw PACIFIC BIOSCIENCES   (United States)

^ax SAGE BIONETWORKS   (United States)

^ay UNIVERSITY OF SPLIT   (Croatia)

^az Gen Info Ltd   (Croatia)

^ba BALTIMORE VA MEDICAL CENTER   (United States)

^bb UPPSALA UNIVERSITY   (Sweden)

^bc ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^bd LUND UNIVERSITY DIABETES CENTRE   (Sweden)

^be NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^bf LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^bg MASSACHUSETTS GENERAL HOSPITAL   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN RECEPTOR SUBSTRATE 1;

ADULT; ARTICLE; BODY FAT; BODY MASS; CORONARY ARTERY DISEASE; DIABETES MELLITUS; DYSLIPIDEMIA; FEMALE; GENETIC VARIABILITY; GENOME; HUMAN; INSULIN RESISTANCE; MAJOR CLINICAL STUDY; MALE; METABOLIC SYNDROME X; OBESITY; PRIORITY JOURNAL; RACE DIFFERENCE; RISK ASSESSMENT; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM;

ADIPONECTIN; ADIPOSITY; ALLELES; BODY FAT DISTRIBUTION; BODY MASS INDEX; BODY WEIGHT; FEMALE; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INSULIN RECEPTOR SUBSTRATE PROTEINS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; META-ANALYSIS AS TOPIC; METABOLOME; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE; SUBCUTANEOUS FAT;

EID: 79960895140     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.866     Document Type: Article

References (51)

1. Anonymous. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ. Tech. Rep. Ser. 894, 1-253 (2000).
2. 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). (Pubitemid 27415169)
3. 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). (Pubitemid 46764279)
4. 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). (Pubitemid 351748863)
5. Scuteri, A. et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 3, e115 (2007).
6. Thorleifsson, G. et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. 41, 18-24 (2009).
7. Willer, C.J. et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 41, 25-34 (2009).
8. Speliotes, E.K. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 42, 937-948 (2010).
9. Teslovich, T.M. et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707-713 (2010).
10. Rung, J. et al. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat. Genet. 41, 1110-1115 (2009).
11. Samani, N.J. et al. Genomewide association analysis of coronary artery disease. N. Engl. J. Med. 357, 443-453 (2007). (Pubitemid 47204873)
12. Matsuda, M. & DeFronzo, R.A. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22, 1462-1470 (1999). (Pubitemid 29418240)
13. Gutt, M. et al. Validation of the insulin sensitivity index (ISI(0,120)): comparison with other measures. Diabetes Res. Clin. Pract. 47, 177-184 (2000). (Pubitemid 30068708)
14. Badman, M.K. & Flier, J.S. The adipocyte as an active participant in energy balance and metabolism. Gastroenterology 132, 2103-2115 (2007). (Pubitemid 46693755)
15. Kim, J.Y. et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J. Clin. Invest. 117, 2621-2637 (2007).
16. Virtue, S. & Vidal-Puig, A. It's not how fat you are, it's what you do with it that counts. PLoS Biol. 6, e237 (2008).
17. Emilsson, V. et al. Genetics of gene expression and its effect on disease. Nature 452, 423-428 (2008). (Pubitemid 351450845)
18. Zhong, H., Yang, X., Kaplan, L.M., Molony, C. & Schadt, E.E. Integrating pathway analysis and genetics of gene expression for genome-wide association studies. Am. J. Hum. Genet. 86, 581-591 (2010).
19. Myers, A.J. et al. A survey of genetic human cortical gene expression. Nat. Genet. 39, 1494-1499 (2007). (Pubitemid 350191339)
20. Cabrita, M.A. & Christofori, G. Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis 11, 53-62 (2008).
21. Yigzaw, Y., Cartin, L., Pierre, S., Scholich, K. & Patel, T.B. The C terminus of sprouty is important for modulation of cellular migration and proliferation. J. Biol. Chem. 276, 22742-22747 (2001).
22. Lee, C.C. et al. Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis. Oncogene 23, 5193-5202 (2004).
23. Zhang, C. et al. Regulation of vascular smooth muscle cell proliferation and migration by human sprouty 2. Arterioscler. Thromb. Vasc. Biol. 25, 533-538 (2005). (Pubitemid 40315674)
24. Urs, S. et al. Sprouty1 is a critical regulatory switch of mesenchymal stem cell lineage allocation. FASEB J. 24, 3264-3273 (2010).
25. Heard-Costa, N.L. et al. NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS Genet. 5, e1000539 (2009).
26. Lindgren, C.M. et al. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet. 5, e1000508 (2009).
27. Meyre, D. et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat. Genet. 41, 157-159 (2009).
28. Scherag, A. et al. Two new loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and German study groups. PLoS Genet. 6, e1000916 (2010).
29. Heid, I.M. et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat. Genet. 42, 949-960 (2010).
30. Grarup, N., Sparso, T. & Hansen, T. Physiologic characterization of type 2 diabetes-related loci. Curr. Diab. Rep. 10, 485-497 (2010).
31. Stumvoll, M. & Jacob, S. Multiple sites of insulin resistance: muscle, liver and adipose tissue. Exp. Clin. Endocrinol. Diabetes 107, 107-110 (1999). (Pubitemid 29179275)
32. Arner, P. Insulin resistance in type 2 diabetes: role of fatty acids. Diabetes Metab. Res. Rev. 18 (Suppl 2) S5-S9 (2002). (Pubitemid 34467308)
33. Wajchenberg, B.L. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr. Rev. 21, 697-738 (2000). (Pubitemid 32113289)
34. Araki, E. et al. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372, 186-190 (1994). (Pubitemid 24347839)
35. Tamemoto, H. et al. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372, 182-186 (1994). (Pubitemid 24347838)
36. Zhou, L. et al. Insulin receptor substrate-2 (IRS-2) can mediate the action of insulin to stimulate translocation of GLUT4 to the cell surface in rat adipose cells. J. Biol. Chem. 272, 29829-29833 (1997).
37. Kaburagi, Y. et al. Role of insulin receptor substrate-1 and pp60 in the regulation of insulin-induced glucose transport and GLUT4 translocation in primary adipocytes. J. Biol. Chem. 272, 25839-25844 (1997). (Pubitemid 27438907)
38. Smith-Hall, J. et al. The 60 kDa insulin receptor substrate functions like an IRS protein (pp60IRS3) in adipose cells. Biochemistry 36, 8304-8310 (1997). (Pubitemid 27297540)
39. Laustsen, P.G. et al. Lipoatrophic diabetes in Irs1Irs3 double knockout mice. Genes Dev. 16, 3213-3222 (2002).
40. Miki, H. et al. Essential role of insulin receptor substrate 1 (IRS-1) and IRS-2 in adipocyte differentiation. Mol. Cell. Biol. 21, 2521-2532 (2001). (Pubitemid 32222104)
41. Tseng, Y.H., Kriauciunas, K.M., Kokkotou, E. & Kahn, C.R. Differential roles of insulin receptor substrates in brown adipocyte differentiation. Mol. Cell. Biol. 24, 1918-1929 (2004). (Pubitemid 38248933)
42. Reich, D., Thangaraj, K., Patterson, N., Price, A.L. & Singh, L. Reconstructing Indian population history. Nature 461, 489-494 (2009).
43. Barnett, A.H. et al. Type 2 diabetes and cardiovascular risk in the UK south Asian community. Diabetologia 49, 2234-2246 (2006). (Pubitemid 44359083)
44. Pruim, R.J. et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26, 2336-2337 (2010).
45. Li, Y. & Mach Abecasis, G.R. 1.0: rapid haplotype reconstruction and missing genotype inference. Am. J. Hum. Genet. S79, 2290 (2006).
46. Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906-913 (2007). (Pubitemid 47014502)
47. Servin, B. & Stephens, M. Imputation-based analysis of association studies: candidate regions and quantitative traits. PLoS Genet. 3, e114 (2007).
48. Chambers, J.C. et al. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat. Genet. 40, 716-718 (2008). (Pubitemid 351748872)
49. Abecasis, G.R., Cherny, S.S., Cookson, W.O. & Cardon, L.R. Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30, 97-101 (2002).
50. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575 (2007). (Pubitemid 47330214)
51. Wang, Z.V., Deng, Y., Wang, Q.A., Sun, K. & Scherer, P.E. Identification and characterization of a promoter cassette conferring adipocyte-specific gene expression. Endocrinology 151, 2933-2939 (2010).