WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk

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Zheng, Hou-Feng (author)

WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk

Article/chapterEnglish2012

Publisher, publication year, extent ...

2012-07-05
SAN FRANCISCO, USA :PUBLIC LIBRARY SCIENCE,2012
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LIBRIS-ID:oai:DiVA.org:umu-57405
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-57405URI
https://doi.org/10.1371/journal.pgen.1002745DOI
https://lup.lub.lu.se/record/3073320URI
https://gup.ub.gu.se/publication/161394URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Hälsovetenskap Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Health Sciences Public Health, Global Health, Social Medicine and Epidemiology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Ortopedi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Orthopaedics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
genetik
Genetics
Orthopaedics
ortopedi

Added entries (persons, corporate bodies, meetings, titles ...)

Tobias, Jon H (author)
Duncan, Emma (author)
Evans, David M (author)
Eriksson, JoelGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xerjoe (author)
Paternoster, Lavinia (author)
Yerges-Armstrong, Laura M (author)
Lehtimäki, Terho (author)
Bergström, UlricaUmeå universitet,Institutionen för kirurgisk och perioperativ vetenskap(Swepub:umu)ulbe0006 (author)
Kähönen, Mika (author)
Leo, Paul J (author)
Raitakari, Olli (author)
Laaksonen, Marika (author)
Nicholson, Geoffrey C (author)
Viikari, Jorma (author)
Ladouceur, Martin (author)
Lyytikäinen, Leo-Pekka (author)
Medina-Gomez, Carolina (author)
Rivadeneira, Fernando (author)
Prince, Richard L (author)
Sievanen, Harri (author)
Leslie, William D (author)
Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xmelda (author)
Eisman, John A (author)
Movérare-Skrtic, SofiaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xmovso (author)
Goltzman, David (author)
Hanley, David A (author)
Jones, Graeme (author)
St Pourcain, Beate (author)
Xiao, Yongjun (author)
Timpson, Nicholas J (author)
Smith, George Davey (author)
Reid, Ian R (author)
Ring, Susan M (author)
Sambrook, Philip N (author)
Karlsson, MagnusLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups(Swepub:lu)orto-mka (author)
Dennison, Elaine M (author)
Kemp, John P (author)
Danoy, Patrick (author)
Sayers, Adrian (author)
Wilson, Scott G (author)
Nethander, Maria,1980Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics(Swepub:gu)xnetma (author)
McCloskey, Eugene (author)
Vandenput, Liesbeth,1974Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xvanli (author)
Eastell, Richard (author)
Liu, Jeff (author)
Spector, Tim (author)
Mitchell, Braxton D (author)
Streeten, Elizabeth A (author)
Brommage, Robert (author)
Pettersson-Kymmer, UlrikaUmeå universitet,Institutionen för folkhälsa och klinisk medicin,Farmakologi(Swepub:umu)ulpe0007 (author)
Brown, Matthew A (author)
Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xohlcl (author)
Richards, J Brent (author)
Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlomat (author)
Göteborgs universitetInstitutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition (creator_code:org_t)

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In:PLoS geneticsSAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE8:7, s. e1002745-1553-7404

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By the author/editor: Zheng, Hou-Feng; Tobias, Jon H; Duncan, Emma; Evans, David M; Eriksson, Joel; Paternoster, Lav ...; show more...; Yerges-Armstrong ...; Lehtimäki, Terho; Bergström, Ulric ...; Kähönen, Mika; Leo, Paul J; Raitakari, Olli; Laaksonen, Marik ...; Nicholson, Geoff ...; Viikari, Jorma; Ladouceur, Marti ...; Lyytikäinen, Leo ...; Medina-Gomez, Ca ...; Rivadeneira, Fer ...; Prince, Richard ...; Sievanen, Harri; Leslie, William ...; Mellström, Dan, ...; Eisman, John A; Movérare-Skrtic, ...; Goltzman, David; Hanley, David A; Jones, Graeme; St Pourcain, Bea ...; Xiao, Yongjun; Timpson, Nichola ...; Smith, George Da ...; Reid, Ian R; Ring, Susan M; Sambrook, Philip ...; Karlsson, Magnus; Dennison, Elaine ...; Kemp, John P; Danoy, Patrick; Sayers, Adrian; Wilson, Scott G; Nethander, Maria ...; McCloskey, Eugen ...; Vandenput, Liesb ...; Eastell, Richard; Liu, Jeff; Spector, Tim; Mitchell, Braxto ...; Streeten, Elizab ...; Brommage, Robert; Pettersson-Kymme ...; Brown, Matthew A; Ohlsson, Claes, ...; Richards, J Bren ...; Lorentzon, Matti ...; show less...

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