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

13 Zitate (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.

Originalsprache	Englisch
Zeitschrift	Human Molecular Genetics
Jahrgang	23
Ausgabenummer	24
Seiten (von - bis)	6684-6693
Seitenumfang	10
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddu386
Publikationsstatus	Veröffentlicht - 15.12.2014
Extern publiziert	Ja

Fördermittel

This work was supported by the Hong Kong Research Grant Council; the Small Project Funding HKU 201309176244 and 201109176063; the Bone Health Fund of HKU Foundation and Matching Grant; the CRCG Grant and the Osteoporosis Research Fund of The University of Hong Kong. The GOOD study was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, COMBINE, the ALF/LUA research grant from the Sahlgrenska University Hospital, the LundbergFoundation,theTorstenandRagnarSöderberg´sFoun-dation, the Novo Nordisk Foundation, the Gustav V and Queen Victoria Freemason Foundation and the European Commission Grant HEALTH-F2 – 2008-201865-GEFOS. The Framingham Heart Study of the NHLBI, NIH and Boston University School of Medicine were supported by the NHLBI’s Framingham Heart Study (N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (N02-HL-6-4278). The WHI work was supported in part by an allocation of computing time from the Ohio Supercomputer Center and the National Institute of General Medical Sciences (U01GM092655) as well as HHSN268201100002C, NO1-6H74316, U54RR0024384 and HHSN268200960002C. The MICROS study was supported by the Ministry of Health and Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, the South Tyrolean Sparkasse Foundation, and the European Union Framework Program 6 EUROSPAN Project (contract no. LSHG-CT-2006-018947). In addition, D.P.K. received support from NIH (Grant R01 AR/AG 41398). E.J.B. received support from the FHS grants 1RO1HL64753, R01HL076784, 1 R01AG028321 and 2R01H L092577.

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10.1093/hmg/ddu386

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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",

publisher = "Oxford University Press",

number = "24",

}

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, Jg. 23, Nr. 24, S. 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.

UR - https://www.scopus.com/pages/publications/84936776293

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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