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  • Walford, G. A.Harvard University,Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA. (författare)

Genome-wide association study of the modified stumvoll insulin sensitivity index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci

  • Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

  • 2016-07-14
  • American Diabetes Association,2016

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/244482
  • https://gup.ub.gu.se/publication/244482URI
  • https://doi.org/10.2337/db16-0199DOI
  • https://lup.lub.lu.se/record/a1089904-0acf-4b54-b9aa-99471a04695cURI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-311224URI

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  • Språk:engelska

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  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding:This work was supported by National Institutes of Health grant DK099249 (to G.A.W.). Grant support was provided to cohorts. For METSIM, the study was funded by the Academy of Finland (grants 77299 and 124243). For Sorbs, the work was supported by grants from the German Research Council (DFG-SFB 1052, "Obesity mechanisms," A01, C01, B03, and SPP 1629 TO 718/2-1), the German Diabetes Association, and the Diabetes Hilfs-und Forschungsfonds Deutschland (DHFD). This work was further supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ (01EO1501, AD2-060E to P.K.), and by the Boehringer Ingelheim Foundation. For FHS, the study was supported by the National Heart, Lung, and Blood Institute (contract nos. N02-HL-6-4278 [supporting its contract with Affymetrix, Inc., for genotyping services], N01-HC-25195, HL084756, and HHSN268201500001I) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK078616 to J.D., U01-DK085526 to H.C. and J.D., 2R01 DK078616 and K24 DK080140 to J.M.). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. A.K.M. was supported by American Diabetes Association Research Foundation (grant 7-12-MN-02). For CHS, research was supported by National Heart, Lung, and Blood Institute contract nos. HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant nos. U01HL080295, HL105756, and HL120393, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). For ULSAM, the project was supported by the Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), the European Research Council (ERC Starting Grant), the Swedish Diabetes Foundation (grant 2013-024), the Swedish Research Council (grant 2012-1397), and the Swedish Heart-Lung Foundation (20120197). A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant WT098017 from the Nordic Center of Excellence in Disease Genetics). For LURIC, the study was supported by the 7th Framework Program (AtheroRemo, grant agreement no. 201668, and RiskyCAD, grant agreement no. 305739) of the European Union and by the INTERREG-IV-Oberrhein-Program (Project A28, Genetic mechanisms of cardiovascular diseases) with support from the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive. M.E.K. and W.M. are supported by the German Federal Ministry of Education and Research as part of the Competence Cluster of Nutrition and Cardiovascular Health (nutriCARD). For Inter99, the study was financially supported by research grants from the Danish Research Council, the Danish Centre for Health Technology Assessment, Novo Nordisk, the Research Foundation of Copenhagen County, Ministry of Internal Affairs and Health of Denmark, the Danish Heart Foundation, the Danish Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen Foundation, the Becket Foundation, and the Danish Diabetes Association. For FUSION, the study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (DK093757, DK072193, DK062370) and the National Human Genome Research Institute (ZIA-HG000024). H.A.K. has received funding from the Academy of Finland (support for clinical research careers, grant no. 258753).Work on the Amish Studies was supported by National Institutes of Health awards K23GM102678 (from National Institute of General Medical Sciences) to J.P.L. and HL084756 (from National Heart, Lung, and Blood Institute) to J.R.O. The Botnia study has been financially supported by grants from the Sigrid Juselius Foundation, the Folkhalsan Research Foundation, the Nordic Center of Excellence in Disease Genetics, a European Union grant (EXGENESIS, GA FP6 2004-005272), the Signe and Ane Gyllenberg Foundation, the Swedish Cultural Foundation in Finland, the Finnish Diabetes Research Foundation, the Foundation for Life and Health in Finland, the Finnish Medical Society, the Paavo Nurmi Foundation, the Helsinki University Central Hospital Research Foundation, the Perklen Foundation, the Ollqvist Foundation, the Narpes Health Care Foundation, and the Ahokas Foundation. The DGI study was further supported by a Swedish Research Council Linne grant (2006-237) and by the Ministry of Education in Finland, the Municipal Health Care Center and Hospital in Jakobstad, and the Health Care Centers in Vasa, Narpes, and Korsholm. The Tubingen study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD e.V.). For the Ely Study, J.L., C. Lang, R.A.S., and N.J.W. acknowledge support from the Medical Research Council (MC_UU_12015/1). The Ely Study was funded by the Medical Research Council (MC_U106179471) and Diabetes UK. Genotyping in the Ely and Fenland studies was supported in part by a Medical Research Council-GlaxoSmithKline pilot program grant (G0701863). For the Birth Cohort 1936 and Inter99 studies, work was support by the Novo Nordisk Foundation Center for Basic Metabolic Research, an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). Work on the Pizarra study was support by Instituto de Salud Carlos III PI11/00880 and Instituto de Salud Carlos III PS09/02117. For Segovia, this work was supported by the Fondo Europeo para el Desarrollo Regional, Red de Centros RCMN (C03/08) grants FEDER 2FD 1997/2309, the Instituto de Salud Carlos III-RETIC RD06/0015/0012, Madrid, Spain (FIS 03/1618); CIBER in Diabetes and Associated Metabolic Disorders (Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion); and the Madrid Autonomous Community (MOIR S2010/BMD-2423), and by educational grants from Eli Lilly Lab, Spain; Bayer Pharmaceutical Co., Spain; and the Fundacion Mutua Madrilena 2008, Spain.De tre första författarna delar förstaförfattarskapet.De två sista författarna delar sistaförfattarskapet.
  • Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci. © 2016 by the American Diabetes Association.

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Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Gustafsson, StefanUppsala universitet,Uppsala University,Institutionen för medicinska vetenskaper(Swepub:uu)stegu732 (författare)
  • Rybin, D.Boston University,Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. (författare)
  • Stancáková, A.University of Eastern Finland,Univ Eastern Finland, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland. (författare)
  • Chen, H.Harvard University,Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. (författare)
  • Liu, C. T.Boston University,Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. (författare)
  • Hong, J.Boston University,Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. (författare)
  • Jensen, R. A.University of Washington,Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Seattle, WA USA. (författare)
  • Rice, K.University of Washington,Yeshiva University,Univ Washington, Dept Biostat, Seattle, WA 98195 USA.,Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.;Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. (författare)
  • Morris, A. P.Wellcome Trust Centre for Human Genetics,Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. (författare)
  • Mägi, R.University of Tartu,Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. (författare)
  • Tönjes, A.Leipzig University,Univ Leipzig, Dept Med, Leipzig, Germany. (författare)
  • Prokopenko, I.University of Oxford,Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Imperial Coll London, Dept Genom Common Dis, London, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. (författare)
  • Kleber, M. E.Heidelberg University,Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany. (författare)
  • Delgado, G.Heidelberg University,Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany. (författare)
  • Silbernagel, G.Medical University of Graz,Med Univ Graz, Dept Internal Med, Div Angiol, Graz, Austria. (författare)
  • Jackson, A. U.University of Michigan,Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. (författare)
  • Appel, E. V.University of Copenhagen,Univ Copenhagen, Fac Hlth & Med Sci, Ctr Basic Metab Res, Novo Nordisk Fdn, Copenhagen, Denmark. (författare)
  • Grarup, N.University of Copenhagen,Univ Copenhagen, Fac Hlth & Med Sci, Ctr Basic Metab Res, Novo Nordisk Fdn, Copenhagen, Denmark. (författare)
  • Lewis, J. P.University of Maryland,Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. (författare)
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  • Ladenvall, ClaesUppsala universitet,Uppsala University,Lund University,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden(Swepub:uu)clala862 (författare)
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Walford, G. A.
Gustafsson, Stef ...
Rybin, D.
Stancáková, A.
Chen, H.
Liu, C. T.
visa fler...
Hong, J.
Jensen, R. A.
Rice, K.
Morris, A. P.
Mägi, R.
Tönjes, A.
Prokopenko, I.
Kleber, M. E.
Delgado, G.
Silbernagel, G.
Jackson, A. U.
Appel, E. V.
Grarup, N.
Lewis, J. P.
Montasser, M. E.
Ladenvall, Claes
Staiger, H.
Luan, J.
Frayling, T. M.
Weedon, M. N.
Xie, W.
Morcillo, S.
Martínez-Larrad, ...
Lind, Lars
Chen, Y. D. I.
Corbaton-Anchuel ...
Færch, K.
Gómez-Zumaquero, ...
Goodarzi, M. O.
Kizer, J. R.
Koistinen, H. A.
Leong, A.
Lind, L.
Lindgren, C.
Machicao, F.
Manning, A. K.
Martín-Núñez, G. ...
Rojo-Martínez, G ...
Rotter, J. I.
Siscovick, D. S.
Zmuda, J. M.
Zhang, Z.
Serrano-Rios, M.
Smith, Ulf, 1943
Soriguer, F.
Hansen, T.
JØrgensen, T. J.
Linnenberg, A.
Pedersen, O.
Walker, M.
Langenberg, C.
Scott, R. A.
Wareham, N. J.
Fritsche, A.
Häring, H. U.
Stefan, N.
Groop, Leif
O'Connell, J. R.
Boehnke, M.
Bergman, R. N.
Collins, F. S.
Mohlke, K. L.
Tuomilehto, J.
März, W.
Kovacs, P.
Stumvoll, M.
Psaty, B. M.
Kuusisto, J.
Laakso, M.
Meigs, J. B.
Dupuis, J.
Ingelsson, Erik
Florez, J. C.
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