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

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

Moayyeri, Alireza (author)

Hsu, Yi-Hsiang (author)

Karasik, David (author)

Estrada, Karol (author)

Xiao, Su-Mei (author)

Nielson, Carrie (author)

Srikanth, Priya (author)

Giroux, Sylvie (author)

Wilson, Scott G. (author)

Zheng, Hou-Feng (author)

Smith, Albert V. (author)

Pye, Stephen R. (author)

Leo, Paul J. (author)

Teumer, Alexander (author)

Hwang, Joo-Yeon (author)

Ohlsson, Claes, 1965 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin,Centre for Bone and Arthritis Research,Institute of Medicine

McGuigan, Fiona (author): Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups

Minster, Ryan L. (author)

Hayward, Caroline (author)

Olmos, Jose M. (author)

Lyytikaeinen, Leo-Pekka (author)

Lewis, Joshua R. (author)

Swart, Karin M. A. (author)

Masi, Laura (author)

Oldmeadow, Chris (author)

Holliday, Elizabeth G. (author)

Cheng, Sulin (author)

Mellström, Dan, 1945 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin,Centre for Bone and Arthritis Research,Institute of Medicine

Harvey, Nicholas C. (author)

Kruk, Marcin (author)

Fabiola Del Greco, M. (author)

Igl, Wilmar (author)

Trummer, Olivia (author)

Grigoriou, Efi (author)

Luben, Robert (author)

Liu, Ching-Ti (author)

Zhou, Yanhua (author)

Oei, Ling (author)

Medina-Gomez, Carolina (author)

Zmuda, Joseph (author)

Tranah, Greg (author)

Brown, Suzanne J. (author)

Williams, Frances M. (author)

Soranzo, Nicole (author)

Jakobsdottir, Johanna (author)

Siggeirsdottir, Kristin (author)

Holliday, Kate L. (author)

Hannemann, Anke (author)

Go, Min Jin (author)

Garcia, Melissa (author)

Polasek, Ozren (author)

Laaksonen, Marika (author)

Zhu, Kun (author)

Enneman, Anke W. (author)

McEvoy, Mark (author)

Peel, Roseanne (author)

Sham, Pak Chung (author)

Jaworski, Maciej (author)

Johansson, Asa (author)

Hicks, Andrew A. (author)

Pludowski, Pawel (author)

Scott, Rodney (author)

Dhonukshe-Rutten, Rosalie A. M. (author)

van der Velde, Nathalie (author)

Kaehoenen, Mika (author)

Viikari, Jorma S. (author)

Sievaenen, Harri (author)

Raitakari, Olli T. (author)

Gonzalez-Macias, Jesus (author)

Hernandez, Jose L. (author)

Mellstroem, Dan (author)

Ljunggren, Östen (author): Uppsala universitet,Endokrinologi och mineralmetabolism

Cho, Yoon Shin (author)

Voelker, Uwe (author)

Nauck, Matthias (author)

Homuth, Georg (author)

Voelzke, Henry (author)

Haring, Robin (author)

Brown, Matthew A. (author)

McCloskey, Eugene (author)

Nicholson, Geoffrey C. (author)

Eastell, Richard (author)

Eisman, John A. (author)

Jones, Graeme (author)

Reid, Ian R. (author)

Dennison, Elaine M. (author)

Wark, John (author)

Boonen, Steven (author)

Vanderschueren, Dirk (author)

Wu, Frederick C. W. (author)

Aspelund, Thor (author)

Richards, J. Brent (author)

Bauer, Doug (author)

Hofman, Albert (author)

Khaw, Kay-Tee (author)

Dedoussis, George (author)

Obermayer-Pietsch, Barbara (author)

Gyllensten, Ulf (author)

Pramstaller, Peter P. (author)

Lorenc, Roman S. (author)

Cooper, Cyrus (author)

Kung, Annie Wai Chee (author)

Lips, Paul (author)

Alen, Markku (author)

Attia, John (author)

Luisa Brandi, Maria (author)

de Groot, Lisette C. P. G. M. (author)

Lehtimaeki, Terho (author)

Riancho, Jose A. (author)

Campbell, Harry (author)

Liu, Yongmei (author)

Harris, Tamara B. (author)

Åkesson, Kristina (author): Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups

Karlsson, Magnus (author): Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups

Lee, Jong-Young (author)

Wallaschofski, Henri (author)

Duncan, Emma L. (author)

O'Neill, Terence W. (author)

Gudnason, Vilmundur (author)

Spector, Timothy D. (author)

Rousseau, Francois (author)

Orwoll, Eric (author)

Cummings, Steven R. (author)

Wareham, Nick J. (author)

Rivadeneira, Fernando (author)

Uitterlinden, Andre G. (author)

Prince, Richard L. (author)

Kiel, Douglas P. (author)

Reeve, Jonathan (author)

Kaptoge, Stephen K. (author)

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(creator_code:org_t)

2014-01-14
2014
English.
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068

Related links:: https://academic.oup...; show more...; http://dx.doi.org/10... (free); https://urn.kb.se/re...; https://doi.org/10.1...; https://lup.lub.lu.s...; https://gup.ub.gu.se...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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 x 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 x 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 x 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Keyword

X-RAY ABSORPTIOMETRY
QUANTITATIVE ULTRASOUND
MINERAL DENSITY
OSTEOPOROSIS
FRACTURE
RISK
DENSITOMETRY
PHENOTYPES
CALCANEUS
WOMEN

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ref (subject category)
art (subject category)

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By the author/editor: Moayyeri, Alirez ...; Hsu, Yi-Hsiang; Karasik, David; Estrada, Karol; Xiao, Su-Mei; Nielson, Carrie; show more...; Srikanth, Priya; Giroux, Sylvie; Wilson, Scott G.; Zheng, Hou-Feng; Smith, Albert V.; Pye, Stephen R.; Leo, Paul J.; Teumer, Alexande ...; Hwang, Joo-Yeon; Ohlsson, Claes, ...; McGuigan, Fiona; Minster, Ryan L.; Hayward, Carolin ...; Olmos, Jose M.; Lyytikaeinen, Le ...; Lewis, Joshua R.; Swart, Karin M. ...; Masi, Laura; Oldmeadow, Chris; Holliday, Elizab ...; Cheng, Sulin; Mellström, Dan, ...; Harvey, Nicholas ...; Kruk, Marcin; Fabiola Del Grec ...; Igl, Wilmar; Trummer, Olivia; Grigoriou, Efi; Luben, Robert; Liu, Ching-Ti; Zhou, Yanhua; Oei, Ling; Medina-Gomez, Ca ...; Zmuda, Joseph; Tranah, Greg; Brown, Suzanne J ...; Williams, France ...; Soranzo, Nicole; Jakobsdottir, Jo ...; Siggeirsdottir, ...; Holliday, Kate L ...; Hannemann, Anke; Go, Min Jin; Garcia, Melissa; Polasek, Ozren; Laaksonen, Marik ...; 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 ...; van der Velde, N ...; Kaehoenen, Mika; Viikari, Jorma S ...; Sievaenen, Harri; Raitakari, Olli ...; Gonzalez-Macias, ...; Hernandez, Jose ...; Mellstroem, Dan; Ljunggren, Östen; Cho, Yoon Shin; Voelker, Uwe; Nauck, Matthias; Homuth, Georg; Voelzke, Henry; Haring, Robin; Brown, Matthew A ...; McCloskey, Eugen ...; Nicholson, Geoff ...; Eastell, Richard; Eisman, John A.; Jones, Graeme; Reid, Ian R.; Dennison, Elaine ...; Wark, John; Boonen, Steven; Vanderschueren, ...; Wu, Frederick C. ...; Aspelund, Thor; Richards, J. Bre ...; Bauer, Doug; Hofman, Albert; Khaw, Kay-Tee; Dedoussis, Georg ...; Obermayer-Pietsc ...; Gyllensten, Ulf; Pramstaller, Pet ...; Lorenc, Roman S.; Cooper, Cyrus; Kung, Annie Wai ...; Lips, Paul; Alen, Markku; Attia, John; Luisa Brandi, Ma ...; de Groot, Lisett ...; Lehtimaeki, Terh ...; Riancho, Jose A.; Campbell, Harry; Liu, Yongmei; Harris, Tamara B ...; Åkesson, Kristin ...; Karlsson, Magnus; Lee, Jong-Young; Wallaschofski, H ...; Duncan, Emma L.; O'Neill, Terence ...; Gudnason, Vilmun ...; Spector, Timothy ...; Rousseau, Franco ...; Orwoll, Eric; Cummings, Steven ...; Wareham, Nick J.; Rivadeneira, Fer ...; Uitterlinden, An ...; Prince, Richard ...; Kiel, Douglas P.; Reeve, Jonathan; Kaptoge, Stephen ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

Articles in the publication: Human Molecular ...

By the university: Uppsala University; Lund University; University of Gothenburg

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