10.3389/fgene.2018.00267.s013 Xueya Zhou Xueya Zhou Ching-Lung Cheung Ching-Lung Cheung Tatsuki Karasugi Tatsuki Karasugi Jaro Karppinen Jaro Karppinen Dino Samartzis Dino Samartzis Yi-Hsiang Hsu Yi-Hsiang Hsu Timothy Shin-Heng Mak Timothy Shin-Heng Mak You-Qiang Song You-Qiang Song Kazuhiro Chiba Kazuhiro Chiba Yoshiharu Kawaguchi Yoshiharu Kawaguchi Yan Li Yan Li Danny Chan Danny Chan Kenneth Man-Chee Cheung Kenneth Man-Chee Cheung Shiro Ikegawa Shiro Ikegawa Kathryn Song-Eng Cheah Kathryn Song-Eng Cheah Pak Chung Sham Pak Chung Sham Table_9_Trans-Ethnic Polygenic Analysis Supports Genetic Overlaps of Lumbar Disc Degeneration With Height, Body Mass Index, and Bone Mineral Density.pdf Frontiers 2018 polygenic score genetic correlation causality pleiotropy lumbar disc degeneration osteoarthritis 2018-08-03 04:25:12 Dataset https://frontiersin.figshare.com/articles/dataset/Table_9_Trans-Ethnic_Polygenic_Analysis_Supports_Genetic_Overlaps_of_Lumbar_Disc_Degeneration_With_Height_Body_Mass_Index_and_Bone_Mineral_Density_pdf/6917216 <p>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, but 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.</p>