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. KielAndrew A. Hicks, Rebecca D. Jackson, Claes Ohlsson, Emelia J. Benjamin, Annie W.C. Kung

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Pages (from-to)6684-6693
Number of pages10
JournalHuman Molecular Genetics
Volume23
Issue number24
DOIs
StatePublished - 15 Dec 2014
Externally publishedYes

Bibliographical note

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© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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