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Title: Genetic analysis identifies DDR2 as a novel gene affecting bone mineral density and osteoporotic fractures in Chinese population
Authors: Guo Y.
Yang T.-L.
Dong S.-S.
Yan H.
Hao R.-H.
Chen X.-F.
Chen J.-B.
Tian Q.
Li J.
Shen H. 
Deng H.-W.
Keywords: discoidin domain receptor 2
messenger RNA
protein tyrosine kinase
unclassified drug
discoidin domain receptor
lectin receptor
protein tyrosine kinase
bone density
controlled study
DDR2 gene
ethnic difference
fragility fracture
gene identification
gene linkage disequilibrium
genetic association
genetic risk
genetic variability
major clinical study
quantitative trait locus
risk assessment
risk factor
single nucleotide polymorphism
Asian continental ancestry group
middle aged
Osteoporotic Fractures
single nucleotide polymorphism
young adult
Asian Continental Ancestry Group
Bone Density
Discoidin Domain Receptors
Middle Aged
Osteoporotic Fractures
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Receptor Protein-Tyrosine Kinases
Receptors, Mitogen
Young Adult
Issue Date: 2015
Citation: Guo Y., Yang T.-L., Dong S.-S., Yan H., Hao R.-H., Chen X.-F., Chen J.-B., Tian Q., Li J., Shen H., Deng H.-W. (2015). Genetic analysis identifies DDR2 as a novel gene affecting bone mineral density and osteoporotic fractures in Chinese population. PLoS ONE 10 (2) : 117102. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: DDR2 gene, playing an essential role in regulating osteoblast differentiation and chondrocyte maturation, may influence bone mineral density (BMD) and osteoporosis, but the genetic variations actually leading to the association remain to be elucidated. Therefore, the aim of this study was to investigate whether the genetic variants in DDR2 are associated with BMD and fracture risk. This study was performed in three samples from two ethnicities, including 1,300 Chinese Han subjects, 700 Chinese Han subjects (350 with osteoporotic hip fractures and 350 healthy controls) and 2,286 US white subjects. Twenty-eight SNPs in DDR2 were genotyped and tested for associations with hip BMD and fractures. We identified 3 SNPs in DDR2 significantly associated with hip BMD in the Chinese population after multiple testing adjustments, which were rs7521233 (P = 1.06×10?4, ?: ?0.018 for allele C), rs7553831 (P = 1.30×10?4, ?: ?0.018 for allele T), and rs6697469 (P = 1.59×10?3, ?: ?0.015 for allele C), separately. These three SNPs were in high linkage disequilibrium. Haplotype analyses detected two significantly associated haplotypes, including one haplotype in block 2 (P = 9.54×10?4, ?: ?0.016) where these three SNPs located. SNP rs6697469 was also associated with hip fractures (P = 0.043, OR: 1.42) in the Chinese population. The effect on fracture risk was consistent with its association with lower BMD. However, in the white population, we didn’t observe significant associations with hip BMD. eQTL analyses revealed that SNPs associated with BMD also affected DDR2 mRNA expression levels in Chinese. Our findings, together with the prior biological evidence, suggest that DDR2 could be a new candidate for osteoporosis in Chinese population. Our results also reveal an ethnic difference, which highlights the need for further genetic studies in each ethnic group. © 2015 Guo et al.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0117102
Rights: Attribution 4.0 International
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