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Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain

Chronic back pain (CBP) is a complex heritable trait and a major cause of disability worldwide. We developed and validated a genome-wide polygenic risk score (PRS) for CBP using a large-scale GWAS based on UK Biobank participants of European ancestry (N = 265,000). The PRS showed poor overall predic...

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Autores principales: Tsepilov, Yakov A., Elgaeva, Elizaveta E., Nostaeva, Arina V., Compte, Roger, Kuznetsov, Ivan A., Karssen, Lennart C., Freidin, Maxim B., Suri, Pradeep, Williams, Frances M. K., Aulchenko, Yurii S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304922/
https://www.ncbi.nlm.nih.gov/pubmed/37373966
http://dx.doi.org/10.3390/jpm13060977
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author Tsepilov, Yakov A.
Elgaeva, Elizaveta E.
Nostaeva, Arina V.
Compte, Roger
Kuznetsov, Ivan A.
Karssen, Lennart C.
Freidin, Maxim B.
Suri, Pradeep
Williams, Frances M. K.
Aulchenko, Yurii S.
author_facet Tsepilov, Yakov A.
Elgaeva, Elizaveta E.
Nostaeva, Arina V.
Compte, Roger
Kuznetsov, Ivan A.
Karssen, Lennart C.
Freidin, Maxim B.
Suri, Pradeep
Williams, Frances M. K.
Aulchenko, Yurii S.
author_sort Tsepilov, Yakov A.
collection PubMed
description Chronic back pain (CBP) is a complex heritable trait and a major cause of disability worldwide. We developed and validated a genome-wide polygenic risk score (PRS) for CBP using a large-scale GWAS based on UK Biobank participants of European ancestry (N = 265,000). The PRS showed poor overall predictive ability (AUC = 0.56 and OR = 1.24 per SD, 95% CI: 1.22–1.26), but individuals from the 99th percentile of PRS distribution had a nearly two-fold increased risk of CBP (OR = 1.82, 95% CI: 1.60–2.06). We validated the PRS on an independent TwinsUK sample, obtaining a similar magnitude of effect. The PRS was significantly associated with various ICD-10 and OPCS-4 diagnostic codes, including chronic ischemic heart disease (OR = 1.1, p-value = 4.8 × 10(−15)), obesity, metabolism-related traits, spine disorders, disc degeneration, and arthritis-related disorders. PRS and environment interaction analysis with twelve known CBP risk factors revealed no significant results, suggesting that the magnitude of G × E interactions with studied factors is small. The limited predictive ability of the PRS that we developed is likely explained by the complexity, heterogeneity, and polygenicity of CBP, for which sample sizes of a few hundred thousand are insufficient to estimate small genetic effects robustly.
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spelling pubmed-103049222023-06-29 Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain Tsepilov, Yakov A. Elgaeva, Elizaveta E. Nostaeva, Arina V. Compte, Roger Kuznetsov, Ivan A. Karssen, Lennart C. Freidin, Maxim B. Suri, Pradeep Williams, Frances M. K. Aulchenko, Yurii S. J Pers Med Article Chronic back pain (CBP) is a complex heritable trait and a major cause of disability worldwide. We developed and validated a genome-wide polygenic risk score (PRS) for CBP using a large-scale GWAS based on UK Biobank participants of European ancestry (N = 265,000). The PRS showed poor overall predictive ability (AUC = 0.56 and OR = 1.24 per SD, 95% CI: 1.22–1.26), but individuals from the 99th percentile of PRS distribution had a nearly two-fold increased risk of CBP (OR = 1.82, 95% CI: 1.60–2.06). We validated the PRS on an independent TwinsUK sample, obtaining a similar magnitude of effect. The PRS was significantly associated with various ICD-10 and OPCS-4 diagnostic codes, including chronic ischemic heart disease (OR = 1.1, p-value = 4.8 × 10(−15)), obesity, metabolism-related traits, spine disorders, disc degeneration, and arthritis-related disorders. PRS and environment interaction analysis with twelve known CBP risk factors revealed no significant results, suggesting that the magnitude of G × E interactions with studied factors is small. The limited predictive ability of the PRS that we developed is likely explained by the complexity, heterogeneity, and polygenicity of CBP, for which sample sizes of a few hundred thousand are insufficient to estimate small genetic effects robustly. MDPI 2023-06-10 /pmc/articles/PMC10304922/ /pubmed/37373966 http://dx.doi.org/10.3390/jpm13060977 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsepilov, Yakov A.
Elgaeva, Elizaveta E.
Nostaeva, Arina V.
Compte, Roger
Kuznetsov, Ivan A.
Karssen, Lennart C.
Freidin, Maxim B.
Suri, Pradeep
Williams, Frances M. K.
Aulchenko, Yurii S.
Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain
title Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain
title_full Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain
title_fullStr Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain
title_full_unstemmed Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain
title_short Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain
title_sort development and replication of a genome-wide polygenic risk score for chronic back pain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304922/
https://www.ncbi.nlm.nih.gov/pubmed/37373966
http://dx.doi.org/10.3390/jpm13060977
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