Hou-Feng Zheng (-); Jon H Tobias (-); Emma Duncan (-); David M Evans (-); Joel Eriksson (Centre for Bone and Arthritis Research & Institutionen för medicin, avdelningen för invärtesmedicin); Lavinia Paternoster (-); Laura M Yerges-Armstrong (-); Terho Lehtimäki (-); Ulrica Bergström (-); Mika Kähönen (-); Paul J Leo (-); Olli Raitakari (-); Marika Laaksonen (-); Geoffrey C Nicholson (-); Jorma Viikari (-); Martin Ladouceur (-); Leo-Pekka Lyytikäinen (-); Carolina Medina-Gomez (-); Fernando Rivadeneira (-); Richard L Prince (-); Harri Sievanen (-); William D Leslie (-); Dan Mellström (Centre for Bone and Arthritis Research & Institutionen för medicin, avdelningen för invärtesmedicin); John A Eisman (-); Sofia Movérare-Skrtic (Centre for Bone and Arthritis Research & Institutionen för medicin, avdelningen för invärtesmedicin); David Goltzman (-); David A Hanley (-); Graeme Jones (-); Beate St Pourcain (-); Yongjun Xiao (-); Nicholas J Timpson (-); George Davey Smith (-); Ian R Reid (-); Susan M Ring (-); Philip N Sambrook (-); Magnus Karlsson (-); Elaine M Dennison (-); John P Kemp (-); Patrick Danoy (-); Adrian Sayers (-); Scott G Wilson (-); Maria Nethander (Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik & Centre for Bone and Arthritis Research); Eugene McCloskey (-); Liesbeth Vandenput (Centre for Bone and Arthritis Research & Institutionen för medicin, avdelningen för invärtesmedicin); Richard Eastell (-); Jeff Liu (-); Tim Spector (-); Braxton D Mitchell (-); Elizabeth A Streeten (-); Robert Brommage (-); Ulrika Pettersson-Kymmer (-); Matthew A Brown (-); Claes Ohlsson (Centre for Bone and Arthritis Research & Institutionen för medicin, avdelningen för invärtesmedicin); J Brent Richards (-); Mattias Lorentzon (Centre for Bone and Arthritis Research & Institutionen för medicin, avdelningen för invärtesmedicin)

PLoS genetics, 8 ( 7 ) s. e1002745

1553-7404

Artikel, refereegranskad vetenskaplig

2012

engelska

http://dx.doi.org/10.1371/journal.pgen.1002745

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)

Ämne (baseras på Högskoleverkets indelning av forskningsämnen):

MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Endokrinologi och diabetes ->
Endokrinologi
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Invärtesmedicin

Postens nummer:

161394

Posten skapad:

2012-08-10 15:38

Posten ändrad:

2012-09-20 10:52

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