Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Moayyeri, Alireza, Hsu, Yi-Hsiang, Karasik, David, Estrada, Karol, Xiao, Su-Mei, Nielson, Carrie, Srikanth, Priya, Giroux, Sylvie, Wilson, Scott G., Zheng, Hou-Feng, Smith, Albert V., Pye, Stephen R., Leo, Paul J., Teumer, Alexander, Hwang, Joo-Yeon, Ohlsson, Claes, McGuigan, Fiona, Minster, Ryan L., Hayward, Caroline, Olmos, Jose M., Lyytikainen, Leo-Pekka, Lewis, Joshua R., Swart, Karin M. A., Masi, Laura, Oldmeadow, Chris, Holliday, Elizabeth G., Cheng, Sulin, van Schoor, Natasja M., Harvey, Nicholas C., Kruk, Marcin, del Greco M, Fabiola, Igl, Wilmar, Trummer, Olivia, Grigoriou, Efi, Luben, Robert, Liu, Ching-Ti, Zhou, Yanhua, Oei, Ling, Medina-Gomez, Carolina, Zmuda, Joseph, Tranah, Greg, Brown, Suzanne J., Williams, Frances M., Soranzo, Nicole, Jakobsdottir, Johanna, Siggeirsdottir, Kristin, Holliday, Kate L., Hannemann, Anke, Go, Min Jin, Garcia, Melissa, Polasek, Ozren, Laaksonen, Marika, Zhu, Kun, Enneman, Anke W., McEvoy, Mark, Peel, Roseanne, Sham, Pak Chung, Jaworski, Maciej, Johansson, Asa, Hicks, Andrew A., Pludowski, Pawel, Scott, Rodney, Dhonukshe-Rutten, Rosalie A. M., van der Velde, Nathalie V., Kaohonen, Mika, Viikari, Jorma S., Sievaonen, Harri, Raitakari, Olli T., Gonzalez-Macias, Jesus, Hernandez, Jose L., Mellstrom, Dan, Ljunggren, Osten, Cho, Yoon Shin, Volker, Uwe, Nauck, Matthias, Homuth, Georg, Volzke, Henry, Haring, Robin, Brown, Matthew A., McCloskey, Eugene, Nicholson, Geoffrey C., Eastell, Richard, Eisman, John A., Jones, Graeme, Reid, Ian R., Dennison, Elaine M., Wark, John, Boonen, Steven, Vanderschueren, Dirk, Wu, Frederick C. W., Aspelund, Thor, Richards, J. Brent, Bauer, Doug, Hofman, Albert, Khaw, Kay-Tee, Dedoussis, George, Obermayer-Pietsch, Barbara, Gyllensten, Ulf, Pramstaller, Peter P., Lorenc, Roman S., Cooper, Cyrus, Kung, Annie Wai Chee, Lips, Paul, Alen, Markku, Attia, John, Brandi, Maria Luisa, de Groot, Lisette C. P. G. M., Lehtimaki, Terho, Riancho, Jose A., Campbell, Harry, Liu, Yongmei, Harris, Tamara B., Akesson, Kristina, Karlsson, Magnus, Lee, Jong-Young, Wallaschofski, Henri, Duncan, Emma L., O'Neill, Terence W., Gudnason, Vilmundur, Spector, Timothy D., Rousseau, Francois, Orwoll, Eric, Cummings, Steven R., Wareham, Nick J., Rivadeneira, Fernando, Uitterlinden, Andre G., Prince, Richard L., Kiel, Douglas P., Reeve, Jonathan and Kaptoge, Stephen K. (2014) Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium. Human Molecular Genetics, 23 11: 3054-3068. doi:10.1093/hmg/ddt675


Author Moayyeri, Alireza
Hsu, Yi-Hsiang
Karasik, David
Estrada, Karol
Xiao, Su-Mei
Nielson, Carrie
Srikanth, Priya
Giroux, Sylvie
Wilson, Scott G.
Zheng, Hou-Feng
Smith, Albert V.
Pye, Stephen R.
Leo, Paul J.
Teumer, Alexander
Hwang, Joo-Yeon
Ohlsson, Claes
McGuigan, Fiona
Minster, Ryan L.
Hayward, Caroline
Olmos, Jose M.
Lyytikainen, Leo-Pekka
Lewis, Joshua R.
Swart, Karin M. A.
Masi, Laura
Oldmeadow, Chris
Holliday, Elizabeth G.
Cheng, Sulin
van Schoor, Natasja M.
Harvey, Nicholas C.
Kruk, Marcin
del Greco M, Fabiola
Igl, Wilmar
Trummer, Olivia
Grigoriou, Efi
Luben, Robert
Liu, Ching-Ti
Zhou, Yanhua
Oei, Ling
Medina-Gomez, Carolina
Zmuda, Joseph
Tranah, Greg
Brown, Suzanne J.
Williams, Frances M.
Soranzo, Nicole
Jakobsdottir, Johanna
Siggeirsdottir, Kristin
Holliday, Kate L.
Hannemann, Anke
Go, Min Jin
Garcia, Melissa
Polasek, Ozren
Laaksonen, Marika
Zhu, Kun
Enneman, Anke W.
McEvoy, Mark
Peel, Roseanne
Sham, Pak Chung
Jaworski, Maciej
Johansson, Asa
Hicks, Andrew A.
Pludowski, Pawel
Scott, Rodney
Dhonukshe-Rutten, Rosalie A. M.
van der Velde, Nathalie V.
Kaohonen, Mika
Viikari, Jorma S.
Sievaonen, Harri
Raitakari, Olli T.
Gonzalez-Macias, Jesus
Hernandez, Jose L.
Mellstrom, Dan
Ljunggren, Osten
Cho, Yoon Shin
Volker, Uwe
Nauck, Matthias
Homuth, Georg
Volzke, Henry
Haring, Robin
Brown, Matthew A.
McCloskey, Eugene
Nicholson, Geoffrey C.
Eastell, Richard
Eisman, John A.
Jones, Graeme
Reid, Ian R.
Dennison, Elaine M.
Wark, John
Boonen, Steven
Vanderschueren, Dirk
Wu, Frederick C. W.
Aspelund, Thor
Richards, J. Brent
Bauer, Doug
Hofman, Albert
Khaw, Kay-Tee
Dedoussis, George
Obermayer-Pietsch, Barbara
Gyllensten, Ulf
Pramstaller, Peter P.
Lorenc, Roman S.
Cooper, Cyrus
Kung, Annie Wai Chee
Lips, Paul
Alen, Markku
Attia, John
Brandi, Maria Luisa
de Groot, Lisette C. P. G. M.
Lehtimaki, Terho
Riancho, Jose A.
Campbell, Harry
Liu, Yongmei
Harris, Tamara B.
Akesson, Kristina
Karlsson, Magnus
Lee, Jong-Young
Wallaschofski, Henri
Duncan, Emma L.
O'Neill, Terence W.
Gudnason, Vilmundur
Spector, Timothy D.
Rousseau, Francois
Orwoll, Eric
Cummings, Steven R.
Wareham, Nick J.
Rivadeneira, Fernando
Uitterlinden, Andre G.
Prince, Richard L.
Kiel, Douglas P.
Reeve, Jonathan
Kaptoge, Stephen K.
Title Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
0964-6906
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.1093/hmg/ddt675
Open Access Status
Volume 23
Issue 11
Start page 3054
End page 3068
Total pages 15
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2015
Language eng
Formatted abstract
Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10−8) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10−14). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10−6 also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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