title: Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels.
abstract: Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10 336 individuals from European and Asian origin, we discovered that variants >100 kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.
authors: Department of Medicine, Department of Psychiatry and.
authors: Johnny S H
authors: JS
authors: Kwan
authors: Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA, Program of Quantitative Genomics, Harvard School of Public Health, Boston, MA, USA, BROAD Institute of the MIT and Harvard, Cambridge, MA, USA.
authors: Yi-Hsiang
authors: YH
authors: Hsu
authors: Department of Medicine.
authors: Ching-Lung
authors: CL
authors: Cheung
authors: Framingham Heart Study of the National, Heart, Lung, and Blood Institute and Boston University, Framingham, MA, USA, Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors: Josée
authors: J
authors: Dupuis
authors: Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany, INSERM U1078, Etablissement Français du Sang, Brest, France.
authors: Aude
authors: A
authors: Saint-Pierre
authors: Centre for Bone and Arthritis Research, Departments of Internal Medicine and Geriatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Joel
authors: J
authors: Eriksson
authors: Department of Pharmacology and.
authors: Samuel K
authors: SK
authors: Handelman
authors: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Ohio State University, Columbus, OH, USA.
authors: Aaron
authors: A
authors: Aragaki
authors: Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
authors: David
authors: D
authors: Karasik
authors: Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany, Department of Neurology, General Central Hospital, Bolzano, Italy, Department of Neurology, University of Lübeck, Lübeck, Germany.
authors: Peter P
authors: PP
authors: Pramstaller
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Charles
authors: C
authors: Kooperberg
authors: Department of Preventive Medicine, University of California San Diego, San Diego, CA, USA.
authors: Andrea Z
authors: AZ
authors: Lacroix
authors: Framingham Heart Study of the National, Heart, Lung, and Blood Institute and Boston University, Framingham, MA, USA, Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors: Martin G
authors: MG
authors: Larson
authors: Department of Medicine.
authors: Kam-Shing
authors: KS
authors: Lau
authors: Centre for Bone and Arthritis Research, Departments of Internal Medicine and Geriatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Mattias
authors: M
authors: Lorentzon
authors: Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
authors: Irene
authors: I
authors: Pichler
authors: Department of Psychiatry and Centre for Genomic Sciences, University of Hong Kong, Pokfulam, Hong Kong.
authors: Pak C
authors: PC
authors: Sham
authors: Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
authors: Daniel
authors: D
authors: Taliun
authors: Centre for Bone and Arthritis Research, Departments of Internal Medicine and Geriatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Liesbeth
authors: L
authors: Vandenput
authors: Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA, BROAD Institute of the MIT and Harvard, Cambridge, MA, USA, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors: Douglas P
authors: DP
authors: Kiel
authors: Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
authors: Andrew A
authors: AA
authors: Hicks
authors: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Ohio State University, Columbus, OH, USA.
authors: Rebecca D
authors: RD
authors: Jackson
authors: Centre for Bone and Arthritis Research, Departments of Internal Medicine and Geriatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Claes
authors: C
authors: Ohlsson
authors: Framingham Heart Study of the National, Heart, Lung, and Blood Institute and Boston University, Framingham, MA, USA, Department of Medicine, Boston University School of Medicine, Boston, MA, USA and.
authors: Emelia J
authors: EJ
authors: Benjamin
authors: Department of Medicine, awckung@hkucc.hku.hk.
authors: Annie W C
authors: AW
authors: Kung
mesh_terms: D044466:Asian People; D002883:Chromosomes, Human, Pair 14 / Q000737:chemistry*; D002886:Chromosomes, Human, Pair 17 / Q000737:chemistry*; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D053244:Osteoprotegerin / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D019655:Quantitative Trait, Heritable; D044465:White People
chemical_list: D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human