TY - JOUR

T1 - Exome sequencing association analysis replicated the role of rare variants of SLC13A1 in back pain

AU - Zorkoltseva, Irina V.

AU - Елгаева, Елизавета Евгеньевна

AU - Kirichenko, Anatoly

AU - Belonogova, Nadezhda M.

AU - Svishcheva, Gulnara R.

AU - Цепилов, Яков Александрович

AU - Axenovich, Tatiana I.

N1 - Conference code: 56

PY - 2024/1

Y1 - 2024/1

N2 - Background: Back pain is the leading cause of disability-related years lived worldwide. Its heritability has been estimated at 40–60%, with half attributed to common genetic variants. Rare and ultra-rare variants are expected to provide additional explanations for missing heritability. In this study, we estimated for the first time the impact of rare and ultra-rare variants on chronic back pain (CBP).Methods: CBP was defined as back pain lasting more than 3 months. Using UK Biobank exome sequencing data (N = 179,000), we performed a gene-based association study including only variants with MAF ≤ 0.01. Ultra-rare variants with MAC ≤ 10 were collapsed and considered as a single variant, which was then used together with all other variants for gene-based association analysis. Four sets of within-gene variants with specific protein-coding properties were used in the analysis.Results: We detected a significant association between CBP and SLC13A1 (p-value = 2.50 × 10-6). The signal was obtained for LoF+missense variants. A rare LoF variant of SLC13A1 has recently been identified as being responsible for another back pain trait, intervertebral disc disorder [Bjornsdottir et al., 2022].Conclusion: We replicated the association between back pain and SLC13A1 and showed that the gene effect on back pain can be explained by both LoF and rare missense variants.Grant References: The study was conducted using the UK Biobank resource. The work was supported by the budget project of the Institute of Cytology and Genetics FWNR-2022-0020, Russian Science Foundation (RSF) No.22-15-20037 and Government of the Novosibirsk region, RSF No.23-25-00209.

AB - Background: Back pain is the leading cause of disability-related years lived worldwide. Its heritability has been estimated at 40–60%, with half attributed to common genetic variants. Rare and ultra-rare variants are expected to provide additional explanations for missing heritability. In this study, we estimated for the first time the impact of rare and ultra-rare variants on chronic back pain (CBP).Methods: CBP was defined as back pain lasting more than 3 months. Using UK Biobank exome sequencing data (N = 179,000), we performed a gene-based association study including only variants with MAF ≤ 0.01. Ultra-rare variants with MAC ≤ 10 were collapsed and considered as a single variant, which was then used together with all other variants for gene-based association analysis. Four sets of within-gene variants with specific protein-coding properties were used in the analysis.Results: We detected a significant association between CBP and SLC13A1 (p-value = 2.50 × 10-6). The signal was obtained for LoF+missense variants. A rare LoF variant of SLC13A1 has recently been identified as being responsible for another back pain trait, intervertebral disc disorder [Bjornsdottir et al., 2022].Conclusion: We replicated the association between back pain and SLC13A1 and showed that the gene effect on back pain can be explained by both LoF and rare missense variants.Grant References: The study was conducted using the UK Biobank resource. The work was supported by the budget project of the Institute of Cytology and Genetics FWNR-2022-0020, Russian Science Foundation (RSF) No.22-15-20037 and Government of the Novosibirsk region, RSF No.23-25-00209.

UR - https://www.nature.com/articles/s41431-023-01481-y

M3 - Conference article

VL - 32

SP - 345

JO - European journal of human genetics

JF - European journal of human genetics

SN - 1018-4813

IS - S1

M1 - EP25.005

T2 - 56th Annual Conference of the European-Society-of-Human-Genetics (ESHG)

Y2 - 10 June 2023 through 13 June 2023

ER -