Peng Peng, Chen Zirong, Zhang Xiaolin, Guo Zhongyin, Dong Fangyong, Xu Yu, He Yue, Guo Dongsheng, Wan Feng
Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Genet. 2021 Oct 19;12:741429. doi: 10.3389/fgene.2021.741429. eCollection 2021.
Despite psychiatric traits were associated with intracranial aneurysms (IAs) in observational studies, their causal relationships remain largely undefined. We aimed to assess the causality between psychiatric traits and IAs. We firstly collected the genome-wide association statistics of IAs (sample size, = 79,429) and ten psychiatric traits from Europeans, including insomnia ( = 1,331,010), mood instability ( = 363,705), anxiety disorder ( = 83,566), major depressive disorder (MDD) ( = 480,359), subjective wellbeing ( = 388,538), attention deficit/hyperactivity disorder (ADHD) ( = 53,293), autism spectrum disorder (ASD) ( = 46,350), bipolar disorder (BIP) ( = 51,710), schizophrenia (SCZ) ( = 105,318), and neuroticism ( = 168,105). We then conducted a series of bi-directional two-sample Mendelian randomization (MR) analyses, of which the Robust Adjusted Profile Score (RAPS) was the primary method to estimate the causal effects between these psychiatric traits and IAs. We found that insomnia exhibited a significant risk effect on IAs with the odds ratio (OR) being 1.22 (95% CI: 1.11-1.34, = 4.61 × 10) from the RAPS method. There was suggestive evidence for risk effect of mood instability on IAs (RAPS, OR = 4.16, 95% CI: 1.02-17.00, = 0.047). However, no clear evidence of causal effects on IAs for the rest eight psychiatric traits (anxiety disorder, MDD, subjective wellbeing, ADHD, ASD, BIP, SCZ, and neuroticism) was identified. In the reverse MR analyses, no causal effects of IAs on psychiatric traits were found. Our findings provide strong evidence for a causal risk effect of insomnia on IAs and suggestive evidence for mood instability as a causal risk effect on IAs. These results could inform the prevention and clinical intervention of IAs.
尽管在观察性研究中精神特质与颅内动脉瘤（IA）相关，但其因果关系仍大多未明确。我们旨在评估精神特质与IA之间的因果关系。我们首先收集了来自欧洲人的IA（样本量 = 79,429）以及十种精神特质的全基因组关联统计数据，包括失眠（ = 1,331,010）、情绪不稳定（ = 363,705）、焦虑症（ = 83,566）、重度抑郁症（MDD）（ = 480,359）、主观幸福感（ = 388,538）、注意力缺陷多动障碍（ADHD）（ = 53,293）、自闭症谱系障碍（ASD）（ = 46,350）、双相情感障碍（BIP）（ = 51,710）、精神分裂症（SCZ）（ = 105,318）和神经质（ = 168,105）。然后我们进行了一系列双向双样本孟德尔随机化（MR）分析，其中稳健调整轮廓评分（RAPS）是估计这些精神特质与IA之间因果效应的主要方法。我们发现，从RAPS方法得出，失眠对IA表现出显著的风险效应，优势比（OR）为1.22（95%置信区间：1.11 - 1.34， = 4.61×10）。有提示性证据表明情绪不稳定对IA有风险效应（RAPS，OR = 4.16，95%置信区间：1.02 - 17.00， = 0.047）。然而，未发现其余八种精神特质（焦虑症、MDD、主观幸福感、ADHD、ASD、BIP、SCZ和神经质）对IA有因果效应的明确证据。在反向MR分析中，未发现IA对精神特质有因果效应。我们的研究结果为失眠对IA的因果风险效应提供了有力证据，为情绪不稳定作为IA的因果风险效应提供了提示性证据。这些结果可为IA的预防和临床干预提供参考。
