Brain-specific genes contribute to chronic but not to acute back pain
Andrey V. Bortsov,
Marc Parisien,
Samar Khoury,
Amy E. Martinsen,
Marie Udnesseter Lie,
Ingrid Heuch,
Kristian Hveem,
John-Anker Zwart,
Bendik S. Winsvold,
Luda Diatchenko
Affiliations
Andrey V. Bortsov
a Department of Anesthesiology, Center for Translational Pain Medicine, Duke University, Durham, NC, USA
Marc Parisien
b Faculty of Dental Medicine and Oral Health Sciences and Department of Anesthesia, Faculty of Medicine and Health Sciences, Alan Edwards Centre for Research on Pain, McGill University; Montreal, QC, Canada
Samar Khoury
b Faculty of Dental Medicine and Oral Health Sciences and Department of Anesthesia, Faculty of Medicine and Health Sciences, Alan Edwards Centre for Research on Pain, McGill University; Montreal, QC, Canada
Amy E. Martinsen
c Department of Public Health and Nursing, K. G. Jebsen Center for Genetic Epidemiology, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Marie Udnesseter Lie
d Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
Ingrid Heuch
e Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
Kristian Hveem
c Department of Public Health and Nursing, K. G. Jebsen Center for Genetic Epidemiology, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
John-Anker Zwart
c Department of Public Health and Nursing, K. G. Jebsen Center for Genetic Epidemiology, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Bendik S. Winsvold
c Department of Public Health and Nursing, K. G. Jebsen Center for Genetic Epidemiology, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Luda Diatchenko
b Faculty of Dental Medicine and Oral Health Sciences and Department of Anesthesia, Faculty of Medicine and Health Sciences, Alan Edwards Centre for Research on Pain, McGill University; Montreal, QC, Canada
Abstract. Introduction:. Back pain is the leading cause of disability worldwide. Although most back pain cases are acute, 20% of acute pain patients experience chronic back pain symptoms. It is unclear whether acute pain and chronic pain have similar or distinct underlying genetic mechanisms. Objectives:. To characterize the molecular and cellular pathways contributing to acute and chronic pain states. Methods:. Cross-sectional observational genome-wide association study. Results:. A total of 375,158 individuals from the UK Biobank cohort were included in the discovery of genome-wide association study. Of those, 70,633 (19%) and 32,209 (9%) individuals met the definition of chronic and acute back pain, respectively. A total of 355 single nucleotide polymorphism grouped into 13 loci reached the genome-wide significance threshold (5x10-8) for chronic back pain, but none for acute. Of these, 7 loci were replicated in the Nord-Trøndelag Health Study (HUNT) cohort (19,760 chronic low back pain cases and 28,674 pain-free controls). Single nucleotide polymorphism heritability was 4.6% (P=1.4x10-78) for chronic back pain and 0.81% (P=1.4x10-8) for acute back pain. Similar differences in heritability estimates between acute and chronic back pain were found in the HUNT cohort: 3.4% (P=0.0011) and 0.6% (P=0.851), respectively. Pathway analyses, tissue-specific heritability enrichment analyses, and epigenetic characterization suggest a substantial genetic contribution to chronic but not acute back pain from the loci predominantly expressed in the central nervous system. Conclusion:. Chronic back pain is substantially more heritable than acute back pain. This heritability is mostly attributed to genes expressed in the brain.
