TY - CONF

T1 - Genetic components of chronic back pain may underpin distinct subtypes of the disease

AU - Елгаева, Елизавета Евгеньевна

AU - Freidin, Maxim B.

AU - Williams, Frances M.K.

AU - Suri, Pradeep

AU - Аульченко, Юрий Сергеевич

AU - Цепилов, Яков Александрович

N1 - Conference code: 55

PY - 2023

Y1 - 2023

N2 - Background/Objectives: Chronic back pain (CBP) is a common debilitating condition with a considerable socioeconomic impact and complex genetic architecture. There is now raising evidence for shared genetic background of various pain conditions. Simultaneously, an existence of unshared genetic factors attributing to specific chronic pain types can be assumed. Here we aimed to study the genetic factors of CBP shared and unshared by various chronic pain phenotypes.Methods: We used UK Biobank GWAS data on chronic pain at various locations (back, neck, hip, knee, stomach, head) and split into a discovery (N = 265,000) and a replication sample (N = 191,000). We applied the SHAHER framework and obtained GWAS results for shared genetic impact trait (SGIT) and unshared genetic impact trait (UGIT) of CBP. Utilizing COJO, we identified the loci associated with SGIT or UGIT of CBP and performed the replication. For functional annotation of the results, we used LDSC regression, DEPICT, VEP, FUMA, SMR-HEIDI and PRS analysis.Results: We revealed nine loci associated with SGIT, four of them considered novel with two replicated. We also found one locus associated with UGIT of CBP reported previously. The functional analyses shown relatedness of SGIT to the nervous system structure, functioning and impairment, while UGIT of CBP seemed to be attributed to the musculoskeletal and immune systems.Conclusion: SGIT is likely to underpin the neurogenic and psychogenic subtypes of CBP and chronic pain traits in general, while UGIT primarily reflects the nocigenic CBP.References:Grants: Data provided within the UK Biobank project #18219.Conflict of Interest: Elizaveta Elgaeva: None declared, Maxim Freidin: None declared, Frances Williams: None declared, Pradeep Suri: None declared, Yury Aulchenko YSA is a founder and co-owner of PolyOmica and PolyKnomics, private organisations that provide services, research, and development in the field of quantitative and statistical genetics and computational genomics., YSA is a founder and co-owner of PolyOmica and PolyKnomics, private organisations that provide services, research, and development in the field of quantitative and statistical genetics and computational genomics., Yakov Tsepilov: None declared.

AB - Background/Objectives: Chronic back pain (CBP) is a common debilitating condition with a considerable socioeconomic impact and complex genetic architecture. There is now raising evidence for shared genetic background of various pain conditions. Simultaneously, an existence of unshared genetic factors attributing to specific chronic pain types can be assumed. Here we aimed to study the genetic factors of CBP shared and unshared by various chronic pain phenotypes.Methods: We used UK Biobank GWAS data on chronic pain at various locations (back, neck, hip, knee, stomach, head) and split into a discovery (N = 265,000) and a replication sample (N = 191,000). We applied the SHAHER framework and obtained GWAS results for shared genetic impact trait (SGIT) and unshared genetic impact trait (UGIT) of CBP. Utilizing COJO, we identified the loci associated with SGIT or UGIT of CBP and performed the replication. For functional annotation of the results, we used LDSC regression, DEPICT, VEP, FUMA, SMR-HEIDI and PRS analysis.Results: We revealed nine loci associated with SGIT, four of them considered novel with two replicated. We also found one locus associated with UGIT of CBP reported previously. The functional analyses shown relatedness of SGIT to the nervous system structure, functioning and impairment, while UGIT of CBP seemed to be attributed to the musculoskeletal and immune systems.Conclusion: SGIT is likely to underpin the neurogenic and psychogenic subtypes of CBP and chronic pain traits in general, while UGIT primarily reflects the nocigenic CBP.References:Grants: Data provided within the UK Biobank project #18219.Conflict of Interest: Elizaveta Elgaeva: None declared, Maxim Freidin: None declared, Frances Williams: None declared, Pradeep Suri: None declared, Yury Aulchenko YSA is a founder and co-owner of PolyOmica and PolyKnomics, private organisations that provide services, research, and development in the field of quantitative and statistical genetics and computational genomics., YSA is a founder and co-owner of PolyOmica and PolyKnomics, private organisations that provide services, research, and development in the field of quantitative and statistical genetics and computational genomics., Yakov Tsepilov: None declared.

UR - https://www.nature.com/articles/s41431-023-01339-3

M3 - Paper

SP - EP25.006

T2 - 55th European-Society-of-Human-Genetics (ESHG) Conference

Y2 - 11 June 2022 through 14 June 2022

ER -