Multiple analyses of large-scale genome-wide association study highlight new risk pathways in lumbar spine bone mineral density.
Osteoporosis is a common human complex disease. It is mainly characterized by low bone mineral density (BMD) and low-trauma osteoporotic fractures (OF). Until now, a large proportion of heritability has yet to be explained. The existing large-scale genome-wide association studies (GWAS) provide strong support for the investigation of osteoporosis mechanisms using pathway analysis. Recent findings showed that different risk pathways may be involved in BMD in different tissues. Here, we conducted multiple pathway analyses of a large-scale lumbar spine BMD GWAS dataset (2,468,080 SNPs and 31,800 samples) using two published gene-based analysis software including ProxyGeneLD and the PLINK. Using BMD genes from ProxyGeneLD, we identified 51 significant KEGG pathways with adjusted P<0.01. Using BMD genes from PLINK, we identified 38 significant KEGG pathways with adjusted P<0.01. Interestingly, 33 pathways are shared in both methods. In summary, we not only identified the known risk pathway such as Wnt signaling, in which the top GWAS variants are significantly enriched, but also highlight some new risk pathways. Interestingly, evidence from further supports the involvement of these pathways in MBD.
Department of Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Jinsong
J
Wei
Departmentof Endocrinology and Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Ming
M
Li
Department of Trauma and Emergency Surgeon, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Feng
F
Gao
Department of Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Rong
R
Zeng
Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China.
Guiyou
G
Liu
Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.|Stroke Center, Neurology & Neurosurgery Division, The Clinical Medicine Research Institute & The First Affiliated Hospital, Jinan University, Guangzhou, China.
Keshen
K
Li
D015519:Bone Density / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D015810:Linkage Disequilibrium; D008159:Lumbar Vertebrae; D010024:Osteoporosis / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
bone mineral density; genome-wide association studies; osteoporosis; pathway analysis