ECTS2013 Oral Communications Osteoporosis pathophysiology and genetics (6 abstracts)
Genome-wide association identifies a new susceptibility locus at 4q35 associated with clinical vertebral fractures in post-menopausal women: the GEFOS-GENOMOS consortium
N Alonso 1 , K Estrada 2 , L Herrera 2 , D Kabir 1 , J M Olmos 3 , C Sanudo 3 , J A Riancho 3 , L Oei 2 , M C Medina-Gomez 2 , L Stenkjaer 4 , L Bjerre 4 , B Langdahl 4 , M A Brown 5 , E L Duncan 5 , M Sims 18 , S Kaptoge 19 , J Reeve 20 , J Lewis 6 , R Prince 6 , S Reppe 7 , O K Olstad 8 , K M Gautvik 8 , N Garcia-Giralt 9 , X Nogues 9 , S Mencej-Bedrac 10 , J Marc 10 , J del Pino 11 , R Gonzalez-Sarmiento 11 , O Wolstein 12 , J Eisman 12 , B Feenstra 13 , M Melbye 13 , O M E Albagha 1 , WTCCC 21 , G Davies 14 , J Starr 14 , I Deary 14 , I Quintela 15, , C Fernandez 15, , A Carracedo 15, , G Lucas 22 , R Elosua 17 , A G Uitterlinden 2 , F Rivadeneira 2 & S H Ralston 1
1Rheumatic Diseases Unit, The Centre for Molecular Medicine, IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK; 2Departments of Internal Medicine and Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands; 3Department of Internal Medicine, Hospital UM Valdecilla, University of Cantabria, Santander, Spain; 4Department of Endocrinology and Internal Medicine THG, Aarhus University Hospital, Aarhus, Denmark; 5University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia; 6School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; 7Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; 8Department of Clinical Biochemistry, Lovisenberg Deacon Hospital, Oslo, Norway; 9Departament of Internal Medicine, Hospital del Mar-IMIM, RETICEF, Universitat Autonoma de Barcelona, Barcelona, Spain; 10Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia;11Unidad de Medicina Molecular, Departamento de Medicina, Universidad de Salamanca, Hospital Universitario de Salamanca, RETICEF, Salamanca, Spain; 12Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia; 13Statens Serum institute, National Institute for Health Data and Disease Control, Copenhagen, Denmark; 14Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; 15Unidade de Xenetica, Facultade de Medicina, Instituto de Medicina Legal, Universidade de Santiago de Compostela, Santiago de Compostela, Spain; 16Fundacion Publica Galega de Medicina Xenomica (FPGMX-SERGAS), CIBER Enfermedades Raras, Santiago de Compostela, Spain; 17Grup d’Epidemiologia i Genetica Cardiovascular, IMIM, Barcelona, Spain; 18Medical Research Council, Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK; 19Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; 20University of Cambridge, Cambridge, UK; 21Wellcome Trust Sanger Institute, Cambridge, UK; 22Unitat de Recerca en Lipids i Epidemiologia Cardiovascular (URLEC), IMIM-Hospital del Mar, Barcelona, Spain.
Vertebral fractures (VF) defined by morphometric analysis of spine radiographs are the most common complication of osteoporosis. Those that come to medical attention, with symptoms such as back pain and kyphosis are termed clinical vertebral fractures (CVF) and account for significant morbidity and mortality. Although much progress was made in identifying loci for bone mineral density, the genetic determinants of CVF remain unclear. Here we present the initial results from a genome wide association (GWAS) study involving 1634 postmenopausal women with CVF recruited from 11 centres in Europe and Australia and 4662 regionally matched female controls. Cases were genotyped on the Illumina Omni Express platform whereas various platforms were used for the controls. We analysed 303 365 SNPs which were directly genotyped in both cases and controls. Standard quality control measures were applied. Each study was analysed separately and the results were combined using inverse-variance meta-analysis. The P value thresholds for suggestive and genome-wide significance were set at 1×10−4 and 5×10−8 respectively. We identified nine loci with suggestive association with CVF (with P values ranging from 7.43×10−5 to 2.5×10−6) and one locus on chromosome 4q35 which was significantly associated with CVF (P=7.28×10−8, odds ratio=1.3 (95% CI 1.18–1.43)), to take account of multiple testing (P<1.64×10−7). The associated SNP lies within the SORBS2 gene which plays a role in osteoclast and osteoblast activity. Expression of SORBS2 in bone biopsies was found to strongly correlate with that of Runx2 and other genes in the BMP pathway. Work is in progress through imputation and direct genotyping to replicate the associations we have observed in further and independent case–control studies. We conclude that this initial GWAS among postmenopausal women identifies nine suggestive and one significant locus for CVF, within a gene that regulates bone cell function.
Article tools
My recent searches
My recently viewed abstracts
Authors
Bone Abstracts
ISSN 2052-1219 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more