Pradeep Suri, Maryam Kazemi Naeini, Patrick J Heagerty, Maxim B Freidin, Isabelle Granville Smith, Elizaveta E Elgaeva, Roger Compte, Yakov A Tsepilov, Frances M K Williams
{"title":"腰椎间盘退变与腰背痛的关系因潜在的疼痛遗传倾向而改变。","authors":"Pradeep Suri, Maryam Kazemi Naeini, Patrick J Heagerty, Maxim B Freidin, Isabelle Granville Smith, Elizaveta E Elgaeva, Roger Compte, Yakov A Tsepilov, Frances M K Williams","doi":"10.1016/j.spinee.2024.05.018","DOIUrl":null,"url":null,"abstract":"<p><strong>Background context: </strong>Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups.</p><p><strong>Purpose: </strong>To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.</p><p><strong>Study design: </strong>Cross-sectional study in UK Biobank (UKB) and Twins UK.</p><p><strong>Patient samples: </strong>A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments.</p><p><strong>Outcome measures: </strong>Ever having had LBP associated with disability lasting ≥1 month (LBP1).</p><p><strong>Methods: </strong>Using the PRS as a proxy for \"genetically-predicted propensity to pain\", we stratified TwinsUK participants into PRS quartiles. A \"basic\" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A \"fully-adjusted\" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms.</p><p><strong>Results: </strong>In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4-2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR=2.5 [95% CI 1.7-3.7], p=2.6×10<sup>-6</sup>), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=.002), with small-magnitude and/or nonsignificant associations in the lowest 2 PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤.05).</p><p><strong>Conclusions: </strong>Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.</p>","PeriodicalId":49484,"journal":{"name":"Spine Journal","volume":" ","pages":"8-17"},"PeriodicalIF":4.9000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637947/pdf/","citationCount":"0","resultStr":"{\"title\":\"The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain.\",\"authors\":\"Pradeep Suri, Maryam Kazemi Naeini, Patrick J Heagerty, Maxim B Freidin, Isabelle Granville Smith, Elizaveta E Elgaeva, Roger Compte, Yakov A Tsepilov, Frances M K Williams\",\"doi\":\"10.1016/j.spinee.2024.05.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background context: </strong>Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups.</p><p><strong>Purpose: </strong>To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.</p><p><strong>Study design: </strong>Cross-sectional study in UK Biobank (UKB) and Twins UK.</p><p><strong>Patient samples: </strong>A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments.</p><p><strong>Outcome measures: </strong>Ever having had LBP associated with disability lasting ≥1 month (LBP1).</p><p><strong>Methods: </strong>Using the PRS as a proxy for \\\"genetically-predicted propensity to pain\\\", we stratified TwinsUK participants into PRS quartiles. A \\\"basic\\\" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A \\\"fully-adjusted\\\" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms.</p><p><strong>Results: </strong>In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4-2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR=2.5 [95% CI 1.7-3.7], p=2.6×10<sup>-6</sup>), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=.002), with small-magnitude and/or nonsignificant associations in the lowest 2 PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤.05).</p><p><strong>Conclusions: </strong>Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.</p>\",\"PeriodicalId\":49484,\"journal\":{\"name\":\"Spine Journal\",\"volume\":\" \",\"pages\":\"8-17\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637947/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Spine Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.spinee.2024.05.018\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Spine Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.spinee.2024.05.018","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain.
Background context: Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups.
Purpose: To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.
Study design: Cross-sectional study in UK Biobank (UKB) and Twins UK.
Patient samples: A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments.
Outcome measures: Ever having had LBP associated with disability lasting ≥1 month (LBP1).
Methods: Using the PRS as a proxy for "genetically-predicted propensity to pain", we stratified TwinsUK participants into PRS quartiles. A "basic" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A "fully-adjusted" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms.
Results: In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4-2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR=2.5 [95% CI 1.7-3.7], p=2.6×10-6), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=.002), with small-magnitude and/or nonsignificant associations in the lowest 2 PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤.05).
Conclusions: Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.
期刊介绍：
The Spine Journal, the official journal of the North American Spine Society, is an international and multidisciplinary journal that publishes original, peer-reviewed articles on research and treatment related to the spine and spine care, including basic science and clinical investigations. It is a condition of publication that manuscripts submitted to The Spine Journal have not been published, and will not be simultaneously submitted or published elsewhere. The Spine Journal also publishes major reviews of specific topics by acknowledged authorities, technical notes, teaching editorials, and other special features, Letters to the Editor-in-Chief are encouraged.
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