title: The Chromosome 9p21 CVD- and T2D-Associated Regions in a Norwegian Population (The HUNT2 Survey).
abstract: Background. Two adjacent regions upstream CDKN2B on chromosome 9p21 have been associated with type 2 diabetes (T2D) and progression of cardiovascular disease (CVD). The precise location and number of risk variants have not been completely delineated and a possible synergistic relationship between the adjacent regions is not fully addressed. By a population based cross-sectional case-control design, we genotyped 18 SNPs upstream of CDKN2B tagging 138 kb in and around two LD-blocks associated with CVD and T2D and investigated associations with T2D, angina pectoris (AP), myocardial infarction (MI), coronary heart disease (CHD; AP or AMI), and stroke using 5,564 subjects from HUNT2. Results. Single point and haplotype analysis showed evidence for only one common T2D risk haplotype (rs10757282∣rs10811661: OR = 1.19, P = 2.0 × 10(-3)) in the region. We confirmed the strong association between SNPs in the 60 kb CVD region with AP, MI, and CHD (P < 0.01). Conditioning on the lead SNPs in the region, we observed two suggestive independent single SNP association signals for MI, rs2065501  (P = 0.03) and rs3217986  (P = 0.04). Conclusions. We confirmed the association of known variants within the 9p21 interval with T2D and CHD. Our results further suggest that additional CHD susceptibility variants exist in this region.
authors.affiliation: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Øyvind
authors.identifier: 0000-0002-5612-2985
authors.initials: Ø
authors.lastname: Helgeland
authors.affiliation: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway ; Morbid Obesity Center, Vestfold Hospital Trust, 3116 Tønsberg, Norway ; Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Jens K
authors.initials: JK
authors.lastname: Hertel
authors.affiliation: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway ; Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Anders
authors.identifier: 0000-0003-1847-3079
authors.initials: A
authors.lastname: Molven
authors.affiliation: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Helge
authors.initials: H
authors.lastname: Ræder
authors.affiliation: HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway ; Department of Internal Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, 7600 Levanger, Norway.
authors.forename: Carl G P
authors.initials: CG
authors.lastname: Platou
authors.affiliation: HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Midthjell
authors.affiliation: HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway.
authors.forename: Kristian
authors.identifier: 0000-0001-8157-9744
authors.initials: K
authors.lastname: Hveem
authors.affiliation: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Ottar
authors.identifier: 0000-0002-4885-1010
authors.initials: O
authors.lastname: Nygård
authors.affiliation: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Pål R
authors.initials: PR
authors.lastname: Njølstad
authors.affiliation: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Stefan
authors.identifier: 0000-0002-2298-7008
authors.initials: S
authors.lastname: Johansson