Causal Relationships Between Social Isolation and Osteoarthritis: A Mendelian Randomization Study in European Population

Abstract

Objective:We aimed to investigate the causal relationships between social isolation and osteoarthritis. Methods: Publicly available genome-wide association study (GWAS) summary statistics of social isolation and osteoarthritis in European population were obtained from the Neale lab Consortium and the Medical Research Council-Integrative Epidemiology Unit (MRC-IEU) consortium, respectively. Single nucleotide polymorphisms (SNPs) associated with the traits were identified by P < 5×10 −8 and linkage disequilibrium r 2 < 0.1. Three Mendelian randomization (MR) methods including the inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were used to assess the potential causal effect of social isolation on osteoarthritis and the potential causal effect of osteoarthritis on social isolation. Leave-one-out analysis and test of directional horizontal pleiotropy via MR-Egger regression were performed as sensitivity analyses. Results: When evaluating the causal effect of social isolation on osteoarthritis, five SNPs (rs12364432, rs13291079, rs2352075, rs4958586, rs599550) significantly associated with social isolation were studied as instruments, and social isolation was found to be causally associated with increased risk of osteoarthritis (odds ratio [OR] 1.197 (95% confidence interval (CI) 1.096-1.308) estimated by the IVW method). When evaluating the causal effect of osteoarthritis on social isolation, six SNPs (rs10405617, rs12133235, rs13107325, rs2290573, rs3771501, rs75621460) significantly associated with osteoarthritis were studied as instruments but no causal effect of osteoarthritis on social isolation was found (OR 1.104 (95% CI 0.887-1.375) estimated by the IVW method). Consistent causal relationships were observed when estimated by the weighted median estimator and MR-Egger regression. Leave-one-out analysis and test of directional horizontal pleiotropy suggested the robustness of the above findings. Conclusion: Social isolation is causally associated with osteoarthritis, and further work is needed to investigate the potential mechanisms.

Causal Factors for Osteoarthritis: A Scoping Review of Mendelian Randomization Studies

“…Further analyses revealed these associations to be partially, although not completely, mediated by BMI and smoking. Genetically predicted levels of social isolation were associated with higher OA risk in the study by Zheng et al (OR 1.20, 95% CI 1.10–1.31) 49 . This study used a five SNP instrument to proxy social isolation, and sensitivity analyses revealed no evidence for pleiotropy.…”

“…Genetically predicted levels of social isolation were associated with higher OA risk in the study by Zheng et al (OR 1.20, 95% CI 1.10-1.31). 49 This study used a five SNP instrument to proxy social isolation, and sensitivity analyses revealed no evidence for pleiotropy. Mediation analyses were not performed to evaluate the mechanism through which social isolation might increase OA risk.…”

The relationship between processed meat, red meat, and risk of types of cancer: A Mendelian randomization study

“…Supplementary material 1 showed the SNP information of four exposures (intake of processed meat, pork, beef and mutton), consisting of the name, chromosome location, genes, function, effect allele (EA), other alleles, and effect allele frequency (EAF). We calculated the F statistic for instrumental variable selection and F statistics were >10, which indicated that we have effectively avoided the bias caused by weak instrumental variables ( Supplementary material 1 ) ( 32 ).…”

Effect of Acute Brief Social Isolation on Visceral Pain

“… 6 Clinical studies, on the other hand, have indicated that those who are socially isolated are more prone to experience pain, such as muscular and joint pain. 20 , 21 For the first time, we examined the impact of social isolation on visceral pain sensitivity. In contrast to the effect of social isolation on somatic pain, social isolation increased the sensitivity of rats to visceral pain.…”