Genome-Wide Association Analysis of Longitudinal Bone Mineral Content Data From the Iowa Bone Development Study |
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| Authors: | Camden P Bay Steven M Levy Kathleen F Janz Brian J Smith John R Shaffer Mary L Marazita Trudy L Burns |
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| Institution: | 1. Center for Clinical Investigation, Brigham & Women''s Hospital, Boston, MA, USA;2. Department of Preventive and Community Dentistry, University of Iowa College of Dentistry, Iowa City, IA, USA;3. Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA;4. Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, USA;5. Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA;6. Department of Biostatistics, University of Iowa College of Public Health, Iowa City, IA, USA;7. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA;8. Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA;9. Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA;10. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA;11. Clinical and Translational Science, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;12. Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA;1. Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece;2. Laboratory for the Research of Musculoskeletal System “Th. Garofalidis,” Medical School, National and Kapodistrian University of Athens, KAT Hospital, Greece;3. Department of Computed Tomography, Asklepeion Voulas Hospital, Athens, Greece;4. First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece;5. Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Airforce and VA Hospital, Athens, Greece;1. University of Wisconsin, Osteoporosis Clinical Research Program, Madison, WI, USA;2. Research and Development Department, Medimaps, Bordeaux, France;3. Center of Bone Diseases, Bone and Joint Department, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland;4. University of Wisconsin, Department of Orthopedics and Rehabilitation, Madison, WI, USA;1. IRCCS Istituto Ortopedico Galeazzi, Milano, Italy;2. Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy;3. Scuola di Specializzazione in Radiodiagnostica, Università degli Studi di Milano, Milano, Italy;4. TECHNOLOGIC Srl, Torino, Italy;5. Sezione di Scienze Radiologiche, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università degli Studi di Palermo, Palermo, Italy;6. Former: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, UO Medicina Nucleare, Milano, Italy;1. Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, USA;2. Department of Medicine, Division of Rheumatology, Medical College of Georgia at Augusta University, Augusta, GA, USA;3. Center of Innovation for Complex Chronic Healthcare, Edward J. Hines, Jr. VA Hospital, Hines, IL, USA;4. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA;5. Department of Biostatistics, University of Illinois, Chicago, IL, USA;6. Department of Mathematics, Northeastern Illinois University, Chicago, IL, USA;7. Public Health Sciences, Stritch School of Medicine, Loyola University, Maywood, IL, USA;8. Department of Medicine, Division of Rheumatology, J. Harold Harrison, MD, Distinguished University Chair in Rheumatology, Medical College of Georgia at Augusta University, Augusta, GA, USA;1. Department of Medicine and Nursing, Federal University of Viçosa (UFV), Viçosa, Minas Gerais, Brazil;2. Postgraduate Program in Nutrition Science, Department of Nutrition and Health, Federal University of Viçosa (UFV), Viçosa, Minas Gerais, Brazil;3. Department of the Locomotor Apparatus, Medical School, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil |
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| Abstract: | The foundation for osteoporosis risk is, in part, established during childhood, adolescence, and young adulthood, all periods of development when bone mass is acquired rapidly. The relative quantity of bone mass accrued is influenced by both lifestyle and genetic factors, although the genetic component is not yet well understood. The purpose of this study was to use a genome-wide association (GWA) analysis to discover single nucleotide polymorphisms (SNPs) associated with: (1) the sex-specific hip bone mineral content at approximately the age of 19 when the amount of bone accrued is near its peak; and (2) the sex-specific rate of hip bone mineral content accrual during the adolescent growth spurt. The Iowa Bone Development Study, a longitudinal cohort study exploring bone health in children, adolescents, and young adults was the source of data. From this cohort, n = 364 (190 females, 174 males) participants were included in GWA analyses to address (1) and n = 258 participants (125 females and 133 males) were included in GWA analyses to address (2). Twenty SNPS were detected having p < 1.0 × 10?5. Of most biologic relevance were 2 suggestive SNPs (rs2051756 and rs2866908) detected in an intron of the DKK2 gene through the GWA analysis that explored peak bone mass in females. |
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