Body Mass Index and the Risk of Rheumatic Disease: Linear and Nonlinear Mendelian Randomization Analyses

IF 11.4 1区医学 Q1 RHEUMATOLOGY

Arthritis & Rheumatology Pub Date : 2023-05-23 DOI:10.1002/art.42613

Torgny Karlsson, Fatemeh Hadizadeh, Mathias Rask-Andersen, Åsa Johansson, Weronica E. Ek

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引用次数: 3

Abstract

Objective

Although the association between obesity and risk of rheumatic disease is well established, the precise causal relation has not been conclusively proven. Here, we estimate the causal effect of body mass index (BMI) on the risk of developing 5 different rheumatic diseases.

Methods

Linear and nonlinear mendelian randomization (MR) were used to estimate the effect of BMI on risk of rheumatic disease, and sex-specific effects were identified. Analyses were performed in 361,952 participants from the UK Biobank cohort for 5 rheumatic diseases: rheumatoid arthritis (n = 8,381 cases), osteoarthritis (n = 87,430), psoriatic arthropathy (n = 933), gout (n = 13,638), and inflammatory spondylitis (n = 4,328).

Results

Using linear MR, we found that 1 SD increase in BMI increases the incidence rate for rheumatoid arthritis (incidence rate ratio [IRR] 1.52 [95% confidence interval (95% CI) 1.36–1.69]), osteoarthritis (IRR 1.49 [95% CI 1.43–1.55]), psoriatic arthropathy (IRR 1.80 [95% CI 1.31–2.48]), gout (IRR 1.73 [95% CI 1.56–1.92]), and inflammatory spondylitis (IRR 1.34 [95% CI 1.14–1.57]) in all individuals. BMI was found to be a stronger risk factor in women compared to men for psoriatic arthropathy (P for sex interaction = 3.3 × 10⁻⁴) and gout (P for sex interaction = 4.3 × 10⁻³), and the effect on osteoarthritis was stronger in premenopausal compared to postmenopausal women (P = 1.8 × 10⁻³). Nonlinear effects of BMI were identified for osteoarthritis and gout in men, and for gout in women. The nonlinearity for gout was also more extreme in men compared to women (P = 0.03).

Conclusion

Higher BMI causes an increased risk for rheumatic disease, an effect that is more pronounced in women for both gout and psoriatic arthropathy. The novel sex- and BMI-specific causal effects identified here provide further insight into rheumatic disease etiology and mark an important step toward personalized medicine.

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体重指数与风湿病风险：线性和非线性孟德尔随机化分析。

目的：尽管肥胖与风湿性疾病风险之间的关系已经得到了很好的证实，但确切的因果关系尚未得到最终证实。在这里，我们估计了体重指数（BMI）对患5种不同风湿性疾病风险的因果影响。方法：采用线性和非线性孟德尔随机化（MR）来估计BMI对风湿性疾病风险的影响，并确定性别特异性影响。对来自英国生物银行队列的361952名参与者进行了5种风湿性疾病的分析：类风湿性关节炎（n=8381例）、骨关节炎（n=87430）、银屑病关节病（n=933）、痛风（n=13638）和炎性脊柱炎（n=4328），我们发现，BMI增加1SD会增加所有个体中类风湿性关节炎（发病率比[IRR]1.52[95%置信区间（95%CI）1.36-1.69]）、骨关节炎（IRR1.49[95%CI 1.43-1.55]）、银屑病关节病（IRR1.80[95%CI 1.31-2.48]）、痛风（IRR1.73[95%CI 1.56-1.92]）和炎性脊柱炎（IRR1.34[95%CI 1.14-1.57]）的发病率。研究发现，与男性相比，BMI是女性银屑病关节病的一个更强的风险因素（性别互动的P=3.3× 10-4）和痛风（性行为的P＝4.3 10-3），并且与绝经后妇女相比，绝经前妇女对骨关节炎的影响更强（P= 1.8倍 10-3）。BMI对男性骨关节炎和痛风以及女性痛风的非线性影响被确定。与女性相比，男性痛风的非线性也更为极端（P= 0.03）。结论：较高的BMI会增加患风湿性疾病的风险，这种影响在女性痛风和银屑病关节病中更为明显。本文确定的新的性别和BMI特异性因果效应为进一步了解风湿性疾病的病因提供了依据，并标志着向个性化医学迈出了重要一步。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Arthritis & Rheumatology RHEUMATOLOGY-

CiteScore

20.90

自引率

3.00%

发文量

371

期刊介绍： Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.