William David Thompson, Subhashisa Swain, Sizheng Steven Zhao, Carol Coupland, Changfu Kuo, Michael Doherty, Weiya Zhang
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To estimate the causal effects, we performed 2-sample multivariable Mendelian Randomisation (MR) analysis. We selected genetic instruments from the largest Genome Wide Association Study of BMI (N = 806,834) and MCP (N = 387,649) and estimated the instruments genetic associations with knee OA in the largest available dataset (62,497 cases and 333,557 control subjects). The multivariable MR was performed using modified inverse-variance weighting methods. Of the 203,410 participants, 6% developed knee OA. Both MCP (OR 1.23, 95% CI; 1.21-1.24) and BMI (1.10, 95% CI; 1.10-1.11) were associated with knee OA diagnosis. The PRC was 6.9% (95% CI; 6.7%-7.1%) for MCP and 21.9% (95% CI; 21.4%-22.5%) for BMI; the combined PRC was 38.8% (95% CI; 37.9%-39.8%). Body mass index and MCP had independent causal effects on knee OA (OR 1.76 [95% CI, 1.64-1.88] and 1.83 [95% CI, 1.54-2.16] per unit change, respectively). In conclusion, peripheral risk factors (eg, BMI) contribute more to the development of knee OA than central risk factors (eg, MCP). Peripheral and central factors are independently causal on knee OA.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Causal associations of central and peripheral risk factors with knee osteoarthritis: a longitudinal and Mendelian Randomisation study using UK Biobank data.\",\"authors\":\"William David Thompson, Subhashisa Swain, Sizheng Steven Zhao, Carol Coupland, Changfu Kuo, Michael Doherty, Weiya Zhang\",\"doi\":\"10.1097/j.pain.0000000000003183\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Abstract: </strong>Our aim was to investigate relative contributions of central and peripheral mechanisms to knee osteoarthritis (OA) diagnosis and their independent causal association with knee OA. We performed longitudinal analysis using data from UK-Biobank participants. Knee OA was defined using International Classification of Diseases manual 10 codes from participants' hospital records. Central mechanisms were proxied using multisite chronic pain (MCP) and peripheral mechanisms using body mass index (BMI). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated, and proportional risk contribution (PRC) was estimated from receiver-operator-characteristic (ROC) analysis. To estimate the causal effects, we performed 2-sample multivariable Mendelian Randomisation (MR) analysis. We selected genetic instruments from the largest Genome Wide Association Study of BMI (N = 806,834) and MCP (N = 387,649) and estimated the instruments genetic associations with knee OA in the largest available dataset (62,497 cases and 333,557 control subjects). The multivariable MR was performed using modified inverse-variance weighting methods. Of the 203,410 participants, 6% developed knee OA. Both MCP (OR 1.23, 95% CI; 1.21-1.24) and BMI (1.10, 95% CI; 1.10-1.11) were associated with knee OA diagnosis. The PRC was 6.9% (95% CI; 6.7%-7.1%) for MCP and 21.9% (95% CI; 21.4%-22.5%) for BMI; the combined PRC was 38.8% (95% CI; 37.9%-39.8%). Body mass index and MCP had independent causal effects on knee OA (OR 1.76 [95% CI, 1.64-1.88] and 1.83 [95% CI, 1.54-2.16] per unit change, respectively). In conclusion, peripheral risk factors (eg, BMI) contribute more to the development of knee OA than central risk factors (eg, MCP). Peripheral and central factors are independently causal on knee OA.</p>\",\"PeriodicalId\":19921,\"journal\":{\"name\":\"PAIN®\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PAIN®\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/j.pain.0000000000003183\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ANESTHESIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PAIN®","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/j.pain.0000000000003183","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
摘要:我们的目的是研究中枢和外周机制对膝关节骨性关节炎(OA)诊断的相对贡献及其与膝关节OA的独立因果关系。我们利用英国生物银行参与者的数据进行了纵向分析。膝关节 OA 是根据参与者医院记录中的国际疾病分类手册 10 代码定义的。中枢机制采用多部位慢性疼痛(MCP),外周机制采用体重指数(BMI)。我们估算了比值比 (OR) 和 95% 置信区间 (CI),并通过受体-操作者-特征(ROC)分析估算了比例风险贡献 (PRC)。为了估计因果效应,我们进行了双样本多变量孟德尔随机(MR)分析。我们从最大的全基因组关联研究(Genome Wide Association Study)中选择了BMI(N = 806,834 )和MCP(N = 387,649 )的遗传工具,并在最大的可用数据集(62,497 例病例和 333,557 例对照受试者)中估计了这些工具与膝关节OA的遗传关联。多变量 MR 采用修正的逆方差加权法进行。在 203,410 名参与者中,6% 患有膝关节 OA。MCP(OR 1.23,95% CI;1.21-1.24)和BMI(1.10,95% CI;1.10-1.11)均与膝关节OA诊断相关。MCP的PRC为6.9%(95% CI;6.7%-7.1%),BMI为21.9%(95% CI;21.4%-22.5%);合并PRC为38.8%(95% CI;37.9%-39.8%)。体重指数和 MCP 对膝关节 OA 有独立的因果效应(每单位变化的 OR 分别为 1.76 [95% CI, 1.64-1.88] 和 1.83 [95% CI, 1.54-2.16])。总之,外周风险因素(如体重指数)比中心风险因素(如 MCP)更容易导致膝关节 OA 的发生。外周和中枢因素对膝关节 OA 的影响是独立的。
Causal associations of central and peripheral risk factors with knee osteoarthritis: a longitudinal and Mendelian Randomisation study using UK Biobank data.
Abstract: Our aim was to investigate relative contributions of central and peripheral mechanisms to knee osteoarthritis (OA) diagnosis and their independent causal association with knee OA. We performed longitudinal analysis using data from UK-Biobank participants. Knee OA was defined using International Classification of Diseases manual 10 codes from participants' hospital records. Central mechanisms were proxied using multisite chronic pain (MCP) and peripheral mechanisms using body mass index (BMI). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated, and proportional risk contribution (PRC) was estimated from receiver-operator-characteristic (ROC) analysis. To estimate the causal effects, we performed 2-sample multivariable Mendelian Randomisation (MR) analysis. We selected genetic instruments from the largest Genome Wide Association Study of BMI (N = 806,834) and MCP (N = 387,649) and estimated the instruments genetic associations with knee OA in the largest available dataset (62,497 cases and 333,557 control subjects). The multivariable MR was performed using modified inverse-variance weighting methods. Of the 203,410 participants, 6% developed knee OA. Both MCP (OR 1.23, 95% CI; 1.21-1.24) and BMI (1.10, 95% CI; 1.10-1.11) were associated with knee OA diagnosis. The PRC was 6.9% (95% CI; 6.7%-7.1%) for MCP and 21.9% (95% CI; 21.4%-22.5%) for BMI; the combined PRC was 38.8% (95% CI; 37.9%-39.8%). Body mass index and MCP had independent causal effects on knee OA (OR 1.76 [95% CI, 1.64-1.88] and 1.83 [95% CI, 1.54-2.16] per unit change, respectively). In conclusion, peripheral risk factors (eg, BMI) contribute more to the development of knee OA than central risk factors (eg, MCP). Peripheral and central factors are independently causal on knee OA.
期刊介绍:
PAIN® is the official publication of the International Association for the Study of Pain and publishes original research on the nature,mechanisms and treatment of pain.PAIN® provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.