Table_1_Ankylosing spondylitis and psychiatric disorders in European population: a Mendelian randomization study.xlsx

BackgroundEpidemiologic evidence has demonstrated a correlation between ankylosing spondylitis and psychiatric disorders. However, little is known about the common genetics and causality of this association. This study aimed to investigate the common genetics and causality between ankylosing spondylitis (AS) and psychiatric disorders.
MethodsA two-sample Mendelian Randomization (MR) analysis was carried out to confirm causal relationships between ankylosing spondylitis and five mental health conditions including major depressive disorder (MDD), anxiety disorder (AXD), schizophrenia (SCZ), bipolar disorder (BIP), and anorexia nervosa (AN). Genetic instrumental variables associated with exposures and outcomes were derived from the largest available summary statistics of genome-wide association studies (GWAS). Bidirectional causal estimation of MR was primarily obtained using the inverse variance weighting (IVW) method. Other MR methods include MR-Egger regression, Weighted Median Estimator (WME), Weighted Mode, Simple Mode, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO). Sensitivity analyses are conducted to estimate the robustness of MR results.
ResultsThe findings suggest that AS may be causally responsible for the risk of developing SCZ (OR = 1.18, 95% confidence interval = (1.06, 1.31), P = 2.58 × 10-3) and AN (OR = 1.32, 95% confidence interval = (1.07, 1.64), P = 9.43 × 10-3). In addition, MDD, AXD, SCZ, AN, and BIP were not inversely causally related to AS (all p > 0.05).
ConclusionOur study provides fresh insights into the relationship between AS and psychiatric disorders (SCZ and AN). Furthermore, it may provide new clues for risk management and preventive interventions for mental disorders in patients with AS.

研究背景
流行病学研究证据表明，强直性脊柱炎（ankylosing spondylitis, AS）与精神疾病之间存在相关性，但目前对于二者关联的共同遗传基础及因果关系仍知之甚少。本研究旨在探究强直性脊柱炎与精神疾病之间的共同遗传基础与因果关联。

研究方法
本研究采用两样本孟德尔随机化（Mendelian Randomization, MR）分析，以验证强直性脊柱炎与5种精神健康疾病之间的因果关系，这5种疾病分别为重度抑郁症（major depressive disorder, MDD）、焦虑障碍（anxiety disorder, AXD）、精神分裂症（schizophrenia, SCZ）、双相情感障碍（bipolar disorder, BIP）以及神经性厌食症（anorexia nervosa, AN）。与暴露因素及结局指标相关的遗传工具变量，均来源于目前已公开的最大规模全基因组关联研究（genome-wide association studies, GWAS）汇总统计数据集。MR双向因果效应估计主要采用逆方差加权（inverse variance weighting, IVW）法进行计算，其余MR分析方法还包括MR-Egger回归、加权中位数估计器（Weighted Median Estimator, WME）、加权众数法、简单众数法以及孟德尔随机化多效性残差和离群值检验（Mendelian randomization pleiotropy residual sum and outlier, MR-PRESSO）。此外还开展了敏感性分析，以评估MR分析结果的稳健性。

研究结果
研究结果表明，AS可能对精神分裂症（SCZ）（比值比OR=1.18，95%置信区间CI=(1.06, 1.31)，P=2.58×10^-3）以及神经性厌食症（AN）（OR=1.32，95%CI=(1.07, 1.64)，P=9.43×10^-3）的发病风险存在因果效应。此外，重度抑郁症（MDD）、焦虑障碍（AXD）、精神分裂症（SCZ）、神经性厌食症（AN）与双相情感障碍（BIP）均未表现出对AS的反向因果关联（所有P值均>0.05）。

研究结论
本研究为强直性脊柱炎与精神疾病（精神分裂症SCZ及神经性厌食症AN）之间的关联提供了全新的研究视角，同时可为强直性脊柱炎患者的精神疾病风险管控与预防干预提供新的研究线索。