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

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

Zheng, Hou-Feng (author)

Tobias, Jon H (author)

Duncan, Emma (author)

Evans, David M (author)

Eriksson, Joel (author): Gothenburg 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

Paternoster, Lavinia (author)

Yerges-Armstrong, Laura M (author)

Lehtimäki, Terho (author)

Bergström, Ulrica (author): Umeå universitet,Institutionen för kirurgisk och perioperativ vetenskap

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, 1945 (author): Gothenburg 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

Eisman, John A (author)

Movérare-Skrtic, Sofia (author): Gothenburg 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

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, 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

Dennison, Elaine M (author)

Kemp, John P (author)

Danoy, Patrick (author)

Sayers, Adrian (author)

Wilson, Scott G (author)

Nethander, Maria, 1980 (author): Gothenburg 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

McCloskey, Eugene (author)

Vandenput, Liesbeth, 1974 (author): Gothenburg 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

Eastell, Richard (author)

Liu, Jeff (author)

Spector, Tim (author)

Mitchell, Braxton D (author)

Streeten, Elizabeth A (author)

Brommage, Robert (author)

Pettersson-Kymmer, Ulrika (author): Umeå universitet,Institutionen för folkhälsa och klinisk medicin,Farmakologi

Brown, Matthew A (author)

Ohlsson, Claes, 1965 (author): Gothenburg 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

Richards, J Brent (author)

Lorentzon, Mattias, 1970 (author): Gothenburg 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

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2012-07-05
2012
English.
In: PLoS genetics. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1553-7404. ; 8:7, s. e1002745-

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Journal article (peer-reviewed)

Abstract Subject headings

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

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)

Keyword

genetik
Genetics
Orthopaedics
ortopedi

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art (subject category)

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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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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Health Sciences; and Public Health Gl ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Orthopaedics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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