PDF(Pubmed)
Abstract：
BACKGROUND: Previous observational studies indicated a complex association between frailty and arthritis.
OBJECTIVE: To investigate the genetic causal relationship between the frailty index and the risk of common arthritis.
METHODS: We performed a large-scale Mendelian randomization (MR) analysis to assess frailty index associations with the risk of common arthritis in the UK Biobank (UKB), and the FinnGen Biobank. Summary genome-wide association statistics for frailty, as defined by the frailty index, and common arthritis including rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PSA), and ankylosing spondylitis (AS). The inverse-variance weight (IVW) method served as the primary MR analysis. Heterogeneity testing and sensitivity analysis were also conducted.
RESULTS: Our results denoted a genetic association between the frailty index with an increased risk of OA, the odds ratio (OR)IVW in the UKB was 1.03 (95% confidence interval [CI]: 1.01-1.05; P = 0.007), and ORIVW was 1.55 (95% CI: 1.16-2.07; P = 0.003) in the FinnGen. For RA, the ORIVW from UKB and FinnGen were 1.03 (1.01-1.05, P = 0.006) and 4.57 (1.35-96.49; P = 0.025) respectively. For PSA, the frailty index was associated with PSA (ORIVW = 4.22 (1.21-14.67), P = 0.023) in FinnGen, not in UKB (P > 0.05). However, no association was found between frailty index and AS (P > 0.05). These results remained consistent across sensitivity assessments.
CONCLUSIONS: This study demonstrated a potential causal relationship that genetic predisposition to frailty index was associated with the risk of arthritis, especially RA, OA, and PSA, not but AS. Our findings enrich the existing body of knowledge on the subject matter.
OBJECTIVE: To investigate the genetic causal relationship between the frailty index and the risk of common arthritis.
METHODS: We performed a large-scale Mendelian randomization (MR) analysis to assess frailty index associations with the risk of common arthritis in the UK Biobank (UKB), and the FinnGen Biobank. Summary genome-wide association statistics for frailty, as defined by the frailty index, and common arthritis including rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PSA), and ankylosing spondylitis (AS). The inverse-variance weight (IVW) method served as the primary MR analysis. Heterogeneity testing and sensitivity analysis were also conducted.
RESULTS: Our results denoted a genetic association between the frailty index with an increased risk of OA, the odds ratio (OR)IVW in the UKB was 1.03 (95% confidence interval [CI]: 1.01-1.05; P = 0.007), and ORIVW was 1.55 (95% CI: 1.16-2.07; P = 0.003) in the FinnGen. For RA, the ORIVW from UKB and FinnGen were 1.03 (1.01-1.05, P = 0.006) and 4.57 (1.35-96.49; P = 0.025) respectively. For PSA, the frailty index was associated with PSA (ORIVW = 4.22 (1.21-14.67), P = 0.023) in FinnGen, not in UKB (P > 0.05). However, no association was found between frailty index and AS (P > 0.05). These results remained consistent across sensitivity assessments.
CONCLUSIONS: This study demonstrated a potential causal relationship that genetic predisposition to frailty index was associated with the risk of arthritis, especially RA, OA, and PSA, not but AS. Our findings enrich the existing body of knowledge on the subject matter.
摘要：
背景：先前的观察性研究表明虚弱与关节炎之间存在复杂的关联。
目的：探讨虚弱指数与常见关节炎发病风险之间的遗传因果关系。
方法：我们进行了大规模孟德尔随机化（MR）分析，以评估英国生物库（UKB）中虚弱指数与常见关节炎风险的关联，还有FinnGen生物库.关于脆弱的全基因组关联统计摘要，由脆弱指数定义，和常见的关节炎，包括类风湿性关节炎（RA），骨关节炎（OA），银屑病关节炎(PSA),强直性脊柱炎（AS）。逆方差权重(IVW)方法作为主要的MR分析。还进行了异质性测试和敏感性分析。
结果：我们的结果表明虚弱指数与OA风险增加之间存在遗传关联，UKB中的比值比（OR）IVW为1.03（95％置信区间[CI]：1.01-1.05；P=0.007），FinnGen的ORIVW为1.55（95%CI：1.16-2.07；P=0.003）。对于RA，UKB和FinnGen的ORIVW分别为1.03（1.01-1.05，P=0.006）和4.57（1.35-96.49；P=0.025）。对于PSA,虚弱指数与PSA相关(ORIVW=4.22(1.21-14.67)，P=0.023）在FinnGen中，不在UKB中(P>0.05)。然而,虚弱指数与AS无相关性(P>0.05)。这些结果在敏感性评估中保持一致。
结论：这项研究证明了一个潜在的因果关系，即虚弱指数的遗传倾向与关节炎的风险有关，尤其是RA,OA,PSA,不是，而是as。我们的发现丰富了该主题的现有知识体系。
目的：探讨虚弱指数与常见关节炎发病风险之间的遗传因果关系。
方法：我们进行了大规模孟德尔随机化（MR）分析，以评估英国生物库（UKB）中虚弱指数与常见关节炎风险的关联，还有FinnGen生物库.关于脆弱的全基因组关联统计摘要，由脆弱指数定义，和常见的关节炎，包括类风湿性关节炎（RA），骨关节炎（OA），银屑病关节炎(PSA),强直性脊柱炎（AS）。逆方差权重(IVW)方法作为主要的MR分析。还进行了异质性测试和敏感性分析。
结果：我们的结果表明虚弱指数与OA风险增加之间存在遗传关联，UKB中的比值比（OR）IVW为1.03（95％置信区间[CI]：1.01-1.05；P=0.007），FinnGen的ORIVW为1.55（95%CI：1.16-2.07；P=0.003）。对于RA，UKB和FinnGen的ORIVW分别为1.03（1.01-1.05，P=0.006）和4.57（1.35-96.49；P=0.025）。对于PSA,虚弱指数与PSA相关(ORIVW=4.22(1.21-14.67)，P=0.023）在FinnGen中，不在UKB中(P>0.05)。然而,虚弱指数与AS无相关性(P>0.05)。这些结果在敏感性评估中保持一致。
结论：这项研究证明了一个潜在的因果关系，即虚弱指数的遗传倾向与关节炎的风险有关，尤其是RA,OA,PSA,不是，而是as。我们的发现丰富了该主题的现有知识体系。
