title: Genetic analysis identifies DDR2 as a novel gene affecting bone mineral density and osteoporotic fractures in Chinese population.
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, β: -0.018 for allele C), rs7553831 (P = 1.30×10-4, β: -0.018 for allele T), and rs6697469 (P = 1.59×10-3, β: -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, β: -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.
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Yan
authors: Y
authors: Guo
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Tie-Lin
authors: TL
authors: Yang
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Shan-Shan
authors: SS
authors: Dong
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Han
authors: H
authors: Yan
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Ruo-Han
authors: RH
authors: Hao
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Xiao-Feng
authors: XF
authors: Chen
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Jia-Bin
authors: JB
authors: Chen
authors: School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors: Qing
authors: Q
authors: Tian
authors: School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors: Jian
authors: J
authors: Li
authors: School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors: Hui
authors: H
authors: Shen
authors: School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors: Hong-Wen
authors: HW
authors: Deng
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D015519:Bone Density; D002681:China / Q000453:epidemiology; D000070818:Discoidin Domain Receptors; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D011975:Receptors, Mitogen / Q000235:genetics*; D055815:Young Adult
chemical_list: D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases