Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels

Johnny S H Kwan; Yi-Hsiang Hsu; Ching-Lung Cheung; Josée Dupuis; Aude Saint-Pierre; Joel Eriksson; Samuel K Handelman; Aaron Aragaki; David Karasik; Peter P Pramstaller; Charles Kooperberg; Andrea Z Lacroix; Martin G Larson; Kam-Shing Lau; Mattias Lorentzon; Irene Pichler; Pak C Sham; Daniel Taliun; Liesbeth Vandenput; Douglas P Kiel; Andrew A Hicks; Rebecca D Jackson; Claes Ohlsson; Emelia J Benjamin; Annie W C Kung

doi:10.1093/hmg/ddu386

Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels

Hum Mol Genet. 2014 Dec 15;23(24):6684-93. doi: 10.1093/hmg/ddu386. Epub 2014 Jul 30.

Authors

Johnny S H Kwan¹, Yi-Hsiang Hsu², Ching-Lung Cheung³, Josée Dupuis⁴, Aude Saint-Pierre⁵, Joel Eriksson⁶, Samuel K Handelman⁷, Aaron Aragaki⁸, David Karasik⁹, Peter P Pramstaller¹⁰, Charles Kooperberg¹¹, Andrea Z Lacroix¹², Martin G Larson⁴, Kam-Shing Lau³, Mattias Lorentzon⁶, Irene Pichler¹³, Pak C Sham¹⁴, Daniel Taliun¹³, Liesbeth Vandenput⁶, Douglas P Kiel¹⁵, Andrew A Hicks¹³, Rebecca D Jackson⁸, Claes Ohlsson⁶, Emelia J Benjamin¹⁶, Annie W C Kung¹⁷

Affiliations

¹ Department of Medicine, Department of Psychiatry and.
² 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.
³ Department of Medicine.
⁴ 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.
⁵ 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.
⁶ Centre for Bone and Arthritis Research, Departments of Internal Medicine and Geriatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷ Department of Pharmacology and.
⁸ Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Ohio State University, Columbus, OH, USA.
⁹ Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
¹⁰ 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.
¹¹ Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹² Department of Preventive Medicine, University of California San Diego, San Diego, CA, USA.
¹³ Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
¹⁴ Department of Psychiatry and Centre for Genomic Sciences, University of Hong Kong, Pokfulam, Hong Kong.
¹⁵ 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.
¹⁶ 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.
¹⁷ Department of Medicine, awckung@hkucc.hku.hk.

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.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Asian People
Chromosomes, Human, Pair 14 / chemistry*
Chromosomes, Human, Pair 17 / chemistry*
Female
Genetic Loci*
Genome, Human
Genome-Wide Association Study
Humans
Male
Osteoprotegerin / blood
Osteoprotegerin / genetics*
Polymorphism, Genetic*
Quantitative Trait, Heritable*
White People

Substances

Osteoprotegerin
TNFRSF11B protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding