Zhang Xueyan, Wang Qiaoling, Cui Fenghua, Wu Xuelian, Zhang Chenming
Department of Ophthalmology, The Jinan Second People's Hospital, Jinan, Shandong, China.
Front Psychiatry. 2024 Aug 21;15:1370670. doi: 10.3389/fpsyt.2024.1370670. eCollection 2024.
Observational studies have suggested at a possible link between keratoconus (KC) and various mental disorders, but the exact direction of causation in these associations remains unclear. This study aims to investigate the potential causal link between KC and three prominent mental conditions: Anxiety, Depression, and Schizophrenia.
Using instrumental variables identified from Genome-wide association study (GWAS) data of European individuals, we conducted bidirectional two-sample Mendelian Randomization (MR) analyses to explore potential causal relationships between KC and the three major mental disorders. We primarily employed the Inverse-Variance Weighted (IVW) method to evaluate causality. In addition, we performed four supplementary MR methods (MR-Egger, Weighted Median, Simple Mode, and Weighted Mode). Furthermore, we conducted various sensitivity analyses to assess heterogeneity, horizontal pleiotropy, and result stability.
Our findings did not reveal any concrete evidence of a causal link between KC and the three major mental disorders, namely anxiety, depression, and schizophrenia [anxiety: odds ratio (OR)=0.997, 95% confidence interval (CI)=0.988-1.008, p = 0.621; depression: OR=1.008, 95% CI=0.999-1.017, p = 0.084; schizophrenia: OR=1.002, 95% CI= 0.984-1.020, p = 0.840]. Similarly, the three major mental disorders were not caustically associated with KC [anxiety: OR=1.014, 95% CI=0.635-1.620, p = 0.953; depression: OR=1.109, 95% CI= 0.749-1.643, p = 0.604; schizophrenia: OR= 0.969, 95% CI= 0.884-1.062, p = 0.497]. The sensitivity analyses indicated that the results remained robust, with no signs of pleiotropy or heterogeneity.
Our study does not support a genetically determined significant causal connection between KC and the three major mental disorders. The increased occurrence of mental disorders observed in KC patients in observational reports likely arises from factors that can be modified. Further research is warranted to unveil the underlying mechanisms behind the associations observed in observational studies.
观察性研究表明圆锥角膜（KC）与各种精神障碍之间可能存在联系，但这些关联中因果关系的确切方向仍不明确。本研究旨在调查KC与三种主要精神疾病：焦虑症、抑郁症和精神分裂症之间的潜在因果联系。
利用从欧洲个体的全基因组关联研究（GWAS）数据中确定的工具变量，我们进行了双向双样本孟德尔随机化（MR）分析，以探索KC与三种主要精神障碍之间的潜在因果关系。我们主要采用逆方差加权（IVW）方法来评估因果关系。此外，我们还进行了四种补充性MR方法（MR-Egger、加权中位数、简单模式和加权模式）。此外，我们还进行了各种敏感性分析，以评估异质性、水平多效性和结果稳定性。
我们的研究结果没有揭示KC与三种主要精神障碍（即焦虑症、抑郁症和精神分裂症）之间存在因果联系的具体证据[焦虑症：优势比（OR）=0.997，95%置信区间（CI）=0.988-1.008，p = 0.621；抑郁症：OR = 1.008，95%CI = 0.999-1.017，p = 0.084；精神分裂症：OR = 1.002，95%CI = 0.984-1.020，p = 0.840]。同样，三种主要精神障碍与KC也没有因果关联[焦虑症：OR = 1.014，95%CI = 0.635-1.620，p = 0.953；抑郁症：OR = 1.109，95%CI = 0.749-1.643，p = 0.604；精神分裂症：OR = 0.969，95%CI = 0.884-1.062，p = 0.497]。敏感性分析表明结果仍然稳健，没有多效性或异质性的迹象。
我们的研究不支持KC与三种主要精神障碍之间存在由基因决定的显著因果联系。观察性报告中KC患者精神障碍发生率增加可能源于可改变的因素。有必要进行进一步研究以揭示观察性研究中所观察到的关联背后的潜在机制。
