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

2014; Oxford University Press; Volume: 23; Issue: 24 Linguagem: Inglês

10.1093/hmg/ddu386

1460-2083

Johnny S. H. Kwan, Yi‐Hsiang Hsu, Ching‐Lung Cheung, Josée Dupuis, Aude Saint-Pierre, Joel Eriksson, Samuel K. Handelman, Aaron K. 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, A W Kung,

NF-κB Signaling Pathways

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.