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Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes.
Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Sulem, Patrick; Helgason, Hannes; Grarup, Niels; Sigurdsson, Asgeir; Helgadottir, Hafdis T; Johannsdottir, Hrefna; Magnusson, Olafur T; Gudjonsson, Sigurjon A; Justesen, Johanne M; Harder, Marie N; Jørgensen, Marit E; Christensen, Cramer; Brandslund, Ivan; Sandbæk, Annelli; Lauritzen, Torsten; Vestergaard, Henrik; Linneberg, Allan; Jørgensen, Torben; Hansen, Torben; Daneshpour, Maryam S; Fallah, Mohammad-Sadegh; Hreidarsson, Astradur B; Sigurdsson, Gunnar; Azizi, Fereidoun; Benediktsson, Rafn; Masson, Gisli; Helgason, Agnar; Kong, Augustine; Gudbjartsson, Daniel F; Pedersen, Oluf; Thorsteinsdottir, Unnur; Stefansson, Kari.
Afiliación
  • Steinthorsdottir V; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Thorleifsson G; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Sulem P; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Helgason H; 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
  • Grarup N; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Sigurdsson A; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Helgadottir HT; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Johannsdottir H; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Magnusson OT; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Gudjonsson SA; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Justesen JM; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Harder MN; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Jørgensen ME; Steno Diabetes Center, Gentofte, Denmark.
  • Christensen C; Department of Internal Medicine and Endocrinology, Vejle Hospital, Vejle, Denmark.
  • Brandslund I; 1] Department of Clinical Biochemistry, Vejle Hospital, Vejle, Denmark. [2] Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
  • Sandbæk A; Department of Public Health, Section of General Practice, University of Aarhus, Aarhus, Denmark.
  • Lauritzen T; Department of Public Health, Section of General Practice, University of Aarhus, Aarhus, Denmark.
  • Vestergaard H; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Linneberg A; Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.
  • Jørgensen T; 1] Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark. [2] Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [3] Faculty of Medicine, University of Aalborg, Aalborg, Denmark.
  • Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Daneshpour MS; Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Fallah MS; Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Hreidarsson AB; Department of Endocrinology and Metabolism, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland.
  • Sigurdsson G; Department of Endocrinology and Metabolism, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland.
  • Azizi F; Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Benediktsson R; Department of Endocrinology and Metabolism, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland.
  • Masson G; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Helgason A; 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Department of Anthropology, University of Iceland, Reykjavik, Iceland.
  • Kong A; 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
  • Gudbjartsson DF; 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
  • Pedersen O; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Thorsteinsdottir U; 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Stefansson K; 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Nat Genet ; 46(3): 294-8, 2014 Mar.
Article en En | MEDLINE | ID: mdl-24464100
Through whole-genome sequencing of 2,630 Icelanders and imputation into 11,114 Icelandic cases and 267,140 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (1.47%) variant in intron 1 of CCND2, rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.53, P = 5.0 × 10(-21)) and is correlated with increased CCND2 expression. Notably, this variant is also associated with both greater height and higher body mass index (1.17 cm per allele, P = 5.5 × 10(-12) and 0.56 kg/m(2) per allele, P = 6.5 × 10(-7), respectively). In addition, two missense variants in PAM, encoding p.Asp563Gly (frequency of 4.98%) and p.Ser539Trp (frequency of 0.65%), confer moderately higher risk of T2D (OR = 1.23, P = 3.9 × 10(-10) and OR = 1.47, P = 1.7 × 10(-5), respectively), and a rare (0.20%) frameshift variant in PDX1, encoding p.Gly218Alafs*12, associates with high risk of T2D (OR = 2.27, P = 7.3 × 10(-7)).
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Variación Genética / Transactivadores / Proteínas de Homeodominio / Amidina-Liasas / Diabetes Mellitus Tipo 2 / Ciclina D2 / Oxigenasas de Función Mixta Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male País/Región como asunto: Asia / Europa Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2014 Tipo del documento: Article País de afiliación: Islandia
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Variación Genética / Transactivadores / Proteínas de Homeodominio / Amidina-Liasas / Diabetes Mellitus Tipo 2 / Ciclina D2 / Oxigenasas de Función Mixta Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male País/Región como asunto: Asia / Europa Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2014 Tipo del documento: Article País de afiliación: Islandia