TY - JOUR

T1 - Multi-Trait Exome-Wide Association Study of Back Pain-Related Phenotypes

AU - Zorkoltseva, Irina V

AU - Elgaeva, Elizaveta E

AU - Belonogova, Nadezhda M

AU - Kirichenko, Anatoliy V

AU - Svishcheva, Gulnara R

AU - Freidin, Maxim B

AU - Williams, Frances M K

AU - Suri, Pradeep

AU - Tsepilov, Yakov A

AU - Axenovich, Tatiana I

N1 - The work of I.V.Z. and A.V.K. was supported by the budget project of the Institute of Cytology and Genetics FWNR-2022-0020. The work of Y.A.T., T.I.A., E.E.E., and N.M.B. was supported by the Russian Science Foundation (RSF) grant No. 22-15-20037 and the Government of the Novosibirsk region. The work of G.R.S. was supported by the Russian Science Foundation (RSF) grant No. 23-25-00209. P.S. 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 U.S. Department of Veterans Affairs, the National Institutes of Health, or the United States Government.

PY - 2023/10/19

Y1 - 2023/10/19

N2 - Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40-60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may offer additional insight. This study utilized exome sequencing data from the UK Biobank to perform a multi-trait gene-based association analysis of three BP-related phenotypes: chronic back pain, dorsalgia, and intervertebral disc disorder. We identified the SLC13A1 gene as a contributor to chronic back pain via loss-of-function (LoF) and missense variants. This gene has been previously detected in two studies. A multi-trait approach uncovered the novel FSCN3 gene and its impact on back pain through LoF variants. This gene deserves attention because it is only the second gene shown to have an effect on back pain due to LoF variants and represents a promising drug target for back pain therapy.

AB - Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40-60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may offer additional insight. This study utilized exome sequencing data from the UK Biobank to perform a multi-trait gene-based association analysis of three BP-related phenotypes: chronic back pain, dorsalgia, and intervertebral disc disorder. We identified the SLC13A1 gene as a contributor to chronic back pain via loss-of-function (LoF) and missense variants. This gene has been previously detected in two studies. A multi-trait approach uncovered the novel FSCN3 gene and its impact on back pain through LoF variants. This gene deserves attention because it is only the second gene shown to have an effect on back pain due to LoF variants and represents a promising drug target for back pain therapy.

KW - Humans

KW - Exome/genetics

KW - Genome-Wide Association Study

KW - Genetic Predisposition to Disease

KW - Phenotype

KW - Back Pain/genetics

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85175274905&origin=inward&txGid=ca14acd792f9c654d6eb8b23a110e209

U2 - 10.3390/genes14101962

DO - 10.3390/genes14101962

M3 - Article

C2 - 37895311

VL - 14

JO - Genes

JF - Genes

SN - 2073-4425

IS - 10

M1 - 1962

ER -