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Zhou, X., Cheung, C.-L., Karasugi, T., Karppinen, J., Samartzis, D., Hsu, Y.-H., … Sham, P. C. (2018). Trans-Ethnic Polygenic Analysis Supports Genetic Overlaps of Lumbar Disc Degeneration With Height, Body Mass Index, and Bone Mineral Density. Frontiers in Genetics, 9.

Trans-ethnic polygenic analysis supports genetic overlaps of lumbar disc degeneration with height, body mass index, and bone mineral density

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Author: Zhou, Xueya1,2; Cheung, Ching-Lung3,4; Karasugi, Tatsuki5;
Organizations: 1Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
2Department of Systems Biology, Department of Pediatrics, Columbia University Medical Center, New York, NY, United States
3Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
4Li Ka Shing Faculty of Medicine, Center for Genomic Sciences, The University of Hong Kong, Hong Kong, Hong Kong
5Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto City, Japan
6Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
7Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
8Hebrew SeniorLife, Institute for Aging Research, Roslindale, MA, United States
9Harvard Medical School, Boston, MA, United States
10Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA, United States
11Li Ka Shing Faculty of Medicine, School of Biomedical Science, The University of Hong Kong, Hong Kong, Hong Kong
12Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
13Department of Orthopaedic Surgery, Toyama University, Toyama Prefecture, Japan
14Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2 MB)
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Language: English
Published: Frontiers Media, 2018
Publish Date: 2019-09-23


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.

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Series: Frontiers in genetics
ISSN: 1664-8021
ISSN-E: 1664-8021
ISSN-L: 1664-8021
Volume: 9
Article number: 267
DOI: 10.3389/fgene.2018.00267
Type of Publication: A1 Journal article – refereed
Field of Science: 3141 Health care science
3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by Research Grant Council of Hong Kong Theme-based Research Scheme Functional Analyses of How Genomic Variation Affect Personal Risk for Degenerative Skeletal Disorders (T12-708/12N), and General Research Fund 776513M, 17128515 and 17124027. GEFOS study was funded by the European Commission (HEALTH-F2-2008-201865 GEFOS). arcOGEN study was funded by a special purpose grant from Arthritis Research UK (grant 18030). We thank Ms. Pei Yu for curating the HKDD phenotype database, and Dr. Eleftheria Zeggini for providing the arcOGEN GWAS summary data.
Copyright information: © 2018 Zhou, Cheung, Karasugi, Karppinen, Samartzis, Hsu, Mak, Song, Chiba, Kawaguchi, Li, Chan, Cheung, Ikegawa, Cheah and Sham. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.