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

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

5 Citations (Scopus)

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 language	English
Journal	Human Molecular Genetics
Volume	23
Issue number	24
Pages (from-to)	6684-6693
Number of pages	10
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddu386
Publication status	Published - 15.12.2014
Externally published	Yes

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Kwan, J. S. H., Hsu, Y. H., Cheung, C. L., Dupuis, J., Saint-Pierre, A., Eriksson, J., Handelman, S. K., Aragaki, A., Karasik, D., Pramstaller, P. P., Kooperberg, C., Lacroix, A. Z., Larson, M. G., Lau, K. S., Lorentzon, M., Pichler, I., Sham, P. C., Taliun, D., Vandenput, L., ... Kung, A. W. C. (2014). Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels. Human Molecular Genetics, 23(24), 6684-6693. https://doi.org/10.1093/hmg/ddu386

@article{b552e11de2a140a6a8d4512b8e282df2,

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. ",

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

year = "2014",

month = dec,

day = "15",

doi = "10.1093/hmg/ddu386",

language = "English",

volume = "23",

pages = "6684--6693",

journal = "Human Molecular Genetics",

issn = "0964-6906",

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Kwan, JSH, Hsu, YH, Cheung, CL, Dupuis, J, Saint-Pierre, A, Eriksson, J, Handelman, SK, Aragaki, A, Karasik, D, Pramstaller, PP, Kooperberg, C, Lacroix, AZ, Larson, MG, Lau, KS, Lorentzon, M, Pichler, I, Sham, PC, Taliun, D, Vandenput, L, Kiel, DP, Hicks, AA, Jackson, RD, Ohlsson, C, Benjamin, EJ & Kung, AWC 2014, 'Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels', Human Molecular Genetics, vol. 23, no. 24, pp. 6684-6693. https://doi.org/10.1093/hmg/ddu386

TY - JOUR

T1 - Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels

AU - Kwan, Johnny S.H.

AU - Hsu, Yi Hsiang

AU - Cheung, Ching Lung

AU - Dupuis, Josée

AU - Saint-Pierre, Aude

AU - Eriksson, Joel

AU - Handelman, Samuel K.

AU - Aragaki, Aaron

AU - Karasik, David

AU - Pramstaller, Peter P.

AU - Kooperberg, Charles

AU - Lacroix, Andrea Z.

AU - Larson, Martin G.

AU - Lau, Kam Shing

AU - Lorentzon, Mattias

AU - Pichler, Irene

AU - Sham, Pak C.

AU - Taliun, Daniel

AU - Vandenput, Liesbeth

AU - Kiel, Douglas P.

AU - Hicks, Andrew A.

AU - Jackson, Rebecca D.

AU - Ohlsson, Claes

AU - Benjamin, Emelia J.

AU - Kung, Annie W.C.

PY - 2014/12/15

Y1 - 2014/12/15

N2 - 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.

AB - 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.

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U2 - 10.1093/hmg/ddu386

DO - 10.1093/hmg/ddu386

M3 - Journal articles

C2 - 25080503

AN - SCOPUS:84936776293

SN - 0964-6906

VL - 23

SP - 6684

EP - 6693

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 24

ER -

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

Abstract

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