TY - JOUR

T1 - Non-coding rare variants in PANX3 are associated with chronic back pain

AU - Belonogova, Nadezhda M

AU - Kirichenko, Anatoly V

AU - Freidin, Maxim B

AU - Williams, Frances M K

AU - Suri, Pradeep

AU - Aulchenko, Yurii S

AU - Axenovich, Tatiana I

AU - Tsepilov, Yakov A

N1 - Acknowledgments: The authors acknowledge the participants and investigators of the FinnGen study. This study was conducted under UK Biobank project approval #18219. The work of N. M. Belonogova was supported by the Russian Foundation for Basic Research (#20-04-00464). The work of A. V. Kirichenko and T. I. Axenovich was supported by the budget project No. FWNR-2022-0020. The work of Y. A. Tsepilov was supported by the Russian Science Foundation (RSF) grant No. 22-15-20037 and Government of the Novosibirsk region. P. Suri is a staff physician at the VA Puget Sound Health Care System and co-director of the Resource Core of the University of Washington Clinical Learning, Evidence and Research (CLEAR) Center for Musculoskeletal Disorders, which is funded by NIH/NIAMS P30AR072572. The contents of this work do not represent the views of the US Department of Veterans Affairs, the National Institutes of Health, or the United States Government. Copyright © 2022 International Association for the Study of Pain.

PY - 2022/9/15

Y1 - 2022/9/15

N2 - Back pain is the leading cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this condition. The impact of genetics is known for the chronic back pain: its heritability is estimated to be at least 40%. Large genome-wide association studies have shown that common variation may account for up to 35% of chronic back pain heritability; rare variants may explain a portion of the heritability not explained by common variants. In this study, we performed the first gene-based association analysis of chronic back pain using UK Biobank imputed data including rare variants with moderate imputation quality. We discovered two genes, SOX5 and PANX3 , influencing chronic back pain. The SOX5 gene is well known back pain gene. The PANX3 gene has not previously been described as having a role in chronic back pain. We showed that the association of PANX3 with chronic back pain is driven by rare non-coding intronic polymorphisms. This result has been replicated on the independent sample from UK Biobank and validated using similar phenotype, dorsalgia, from FinnGen Biobank. We also found that the PANX3 gene is associated with intervertebral disc disorders. We can speculate that a possible mechanism of action of the PANX3 on the back pain is due to its effect on the intervertebral discs.

AB - Back pain is the leading cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this condition. The impact of genetics is known for the chronic back pain: its heritability is estimated to be at least 40%. Large genome-wide association studies have shown that common variation may account for up to 35% of chronic back pain heritability; rare variants may explain a portion of the heritability not explained by common variants. In this study, we performed the first gene-based association analysis of chronic back pain using UK Biobank imputed data including rare variants with moderate imputation quality. We discovered two genes, SOX5 and PANX3 , influencing chronic back pain. The SOX5 gene is well known back pain gene. The PANX3 gene has not previously been described as having a role in chronic back pain. We showed that the association of PANX3 with chronic back pain is driven by rare non-coding intronic polymorphisms. This result has been replicated on the independent sample from UK Biobank and validated using similar phenotype, dorsalgia, from FinnGen Biobank. We also found that the PANX3 gene is associated with intervertebral disc disorders. We can speculate that a possible mechanism of action of the PANX3 on the back pain is due to its effect on the intervertebral discs.

KW - Back Pain/genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Introns

KW - Phenotype

KW - Polymorphism, Single Nucleotide/genetics

UR - https://www.mendeley.com/catalogue/5eb3ccd4-8dac-342d-869b-ace1f5e129d3/

U2 - 10.1097/j.pain.0000000000002781

DO - 10.1097/j.pain.0000000000002781

M3 - Article

C2 - 36448979

VL - 164

SP - 864

EP - 869

JO - Pain

JF - Pain

SN - 0304-3959

IS - 4

ER -