Genes Identified that are Associated amongst Risk of Fracture

In the report outlined below, genes were identified that are associated amongst increased peril of fracture.  Importantly, vi genes NOT known to conduct maintain a purpose inward os biological scientific discipline were institute to correlate amongst os mineral density.  This speaks to the importance of looking for diseases related genes inside AND exterior of known pathways.  See abstract below.

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Genome-wide meta-analysis identifies 56 os mineral density loci together with reveals xiv loci associated amongst peril of fracture

• Karol Estrada,
• Unnur Styrkarsdottir,
• Evangelos Evangelou,
• Yi-Hsiang Hsu,
• Emma L Duncan,
• Evangelia E Ntzani,
• Ling Oei,
• Omar grand E Albagha,
• Najaf Amin,
• John P Kemp,
• Daniel L Koller,
• Guo Li,
• Ching-Ti Liu,
• Ryan L Minster,
• Alireza Moayyeri,
• Liesbeth Vandenput,
• Dana Willner,
• Su-Mei Xiao,
• Laura grand Yerges-Armstrong,
• Hou-Feng Zheng,
• Nerea Alonso,
• Joel Eriksson,
• Candace grand Kammerer,
• Stephen K Kaptoge,
• Paul J Leo
• et al.

Nature Genetics

 

44,

 

491–501

 

(2012)

Received

 

07 Oct 2011 

Accepted

 

16 March 2012 

Published online

 

15 Apr 2012

Bone mineral density (BMD) is the nigh widely used predictor of fracture risk. We performed the largest meta-analysis to engagement on lumbar spine together with femoral cervix BMD, including 17 genome-wide association studies together with 32,961 individuals of European together with eastward Asian ancestry. We tested the transcend BMD-associated markers for replication inward 50,933 independent subjects together with for association amongst peril of low-trauma fracture inward 31,016 individuals amongst a history of fracture (cases) together with 102,444 controls. We identified 56 loci (32 new) associated amongst BMD at genome-wide significance (P < five × 10⁻⁸). Several of these factors cluster inside the RANK-RANKL-OPG, mesenchymal stalk jail cellular telephone differentiation, endochondral ossification together with Wnt signaling pathways. However, nosotros likewise discovered loci that were localized to genes non known to conduct maintain a purpose inward os biology. Fourteen BMD-associated loci were likewise associated amongst fracture peril (P < five × 10⁻⁴, Bonferroni corrected), of which vi reached P < five × 10⁻⁸, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) together with 10q21.1 (DKK1). These findings shed low-cal on the genetic architecture together with pathophysiological mechanisms underlying BMD variation together with fracture susceptibility.
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