Trans-ethnic polygenic analysis supports genetic overlaps of lumbar disc degeneration with height, body mass index, and bone mineral density
Trans-ethnic polygenic analysis supports genetic overlaps of lumbar disc degeneration with height, body mass index, and bone mineral density
Abstract Lumbar disc degeneration (LDD) is age-related break-down in the fibrocartilaginous joints between lumbar vertebrae. It is a major cause of low back pain and is conventionally assessed by magnetic resonance imaging (MRI). Like most other complex traits, LDD is likely polygenic and influenced by both genetic and environmental factors. However, genome-wide association studies (GWASs) of LDD have uncovered few susceptibility loci due to the limited sample size. Previous epidemiology studies of LDD also reported multiple heritable risk factors, including height, body mass index (BMI), bone mineral density (BMD), lipid levels, etc. Genetics can help elucidate causality between traits and suggest loci with pleiotropic effects. One such approach is polygenic score (PGS) which summarizes the effect of multiple variants by the summation of alleles weighted by estimated effects from GWAS. To investigate genetic overlaps of LDD and related heritable risk factors, we calculated the PGS of height, BMI, BMD and lipid levels in a Chinese population-based cohort with spine MRI examination and a Japanese case-control cohort of lumbar disc herniation (LDH) requiring surgery. Because most large-scale GWASs were done in European populations, PGS of corresponding traits were created using weights from European GWASs. We calibrated their prediction performance in independent Chinese samples, then tested associations with MRI-derived LDD scores and LDH affection status. The PGS of height, BMI, BMD and lipid levels were strongly associated with respective phenotypes in Chinese, although phenotype variances explained were lower than in Europeans which would reduce the power to detect genetic overlaps. Despite of this, the PGS of BMI and lumbar spine BMD were significantly associated with LDD scores; and the PGS of height was associated with the increased the liability of LDH. Furthermore, linkage disequilibrium score regression suggested that, osteoarthritis, another degenerative disorder that shares common features with LDD, also showed genetic correlations with height, BMI and BMD. The findings suggest a common key contribution of biomechanical stress to the pathogenesis of LDD and will direct the future search for pleiotropic genes.
Chan Danny、Karasugi Tatsuki、Karppinen Jaro、Hsu Yi-Hsiang、Chiba Kazuhiro、Ikegawa Shiro、Kawaguchi Yoshiharu、Li Yan、Cheung Ching-Lung、Song You-Qiang、Mak Timothy Shin-Heng、Samartzis Dino、Zhou Xueya、Cheah Kathryn Song-Eng、Cheung Kenneth Man-Chee、Sham Pak Chung
School of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto UniversityMedical Research Center Oulu, University of Oulu and Oulu University HospitalHebrew SeniorLife, Institute for Aging Research||Harvard Medical School||Molecular and Integrative Physiological Sciences Program, Harvard School of Public HealthDepartment of Orthopedic Surgery, National Defense Medical CollegeLaboratory of Bone and Joint Diseases, Center for Integrative Medical SciencesDepartment of Orthopaedic Surgery, Toyama UniversityDepartment of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong||Center for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong KongCenter for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong||School of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong KongCenter for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong KongSchool of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong||Center for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong
基础医学医学研究方法遗传学
polygenic scoregenetic correlationcausalitypleiotropylumbar disc degenerationosteoarthritis
Chan Danny,Karasugi Tatsuki,Karppinen Jaro,Hsu Yi-Hsiang,Chiba Kazuhiro,Ikegawa Shiro,Kawaguchi Yoshiharu,Li Yan,Cheung Ching-Lung,Song You-Qiang,Mak Timothy Shin-Heng,Samartzis Dino,Zhou Xueya,Cheah Kathryn Song-Eng,Cheung Kenneth Man-Chee,Sham Pak Chung.Trans-ethnic polygenic analysis supports genetic overlaps of lumbar disc degeneration with height, body mass index, and bone mineral density[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/316737.点此复制
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