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探索晨型昼夜偏好与精神障碍之间的因果关联:一项双向双样本孟德尔随机化分析。

Exploring the Causal Association between Morning Diurnal Preference and Psychiatric Disorders: A Bidirectional Two-Sample Mendelian Randomization Analysis.

作者信息

Chen Manman, Tan Din-Son, Wang Xijie, Ye Zichen, Xie Zhilan, Zhang Daqian, Wu Dandan, Zhao Yuankai, Qu Yimin, Jiang Yu

机构信息

School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Vanke School of Public Health & Institute for Healthy China, Tsinghua University, Beijing 100084, China.

出版信息

Life (Basel). 2024 Sep 25;14(10):1225. doi: 10.3390/life14101225.

Abstract

BACKGROUND

The causal connection between morning diurnal preference and psychiatric disorders remains enigmatic. Using bidirectional two-sample Mendelian randomization (MR), we aim to explore the potential causal associations between morning diurnal preference and seven prominent psychiatric disorders.

METHODS

MR is a genetic epidemiological method that leverages genetic variants as instrumental variables to infer causal associations between exposures and outcomes. We obtained morning diurnal preference data from genome-wide association study (GWAS) datasets and identified 252,287 individuals as morning people. Psychiatric disorder data were sourced from the FinnGen consortium R9 dataset. Our primary analysis used the inverse-variance weighted (IVW) approach to evaluate the overall causal effect by combining the estimates from each genetic variant. Addition analyses, including weighted median, MR-Egger regression, weighted mode, and simple mode techniques were conducted to ensure robustness.

RESULTS

Being a morning person is related to reduced odds of multiple psychiatric disorders, including depression or dysthymia (OR: 0.93, 95% CI: 0.88, 0.999), anxiety disorders (OR: 0.90, 95% CI: 0.84, 0.96), self-harming behaviors (OR: 0.87, 95% CI: 0.76, 0.99), substance-use disorders (OR: 0.81, 95% CI: 0.71, 0.93), alcohol dependence (OR: 0.82, 95% CI: 0.73, 0.92), alcohol use disorders (OR: 0.85, 95% CI: 0.76, 0.94), acute alcohol intoxication (OR: 0.86, 95% CI: 0.76, 0.96), schizophrenia (OR: 0.77, 95% CI: 0.65, 0.92), and schizophrenia or delusion (OR: 0.80, 95% CI: 0.70, 0.92). Alcohol dependence (OR: 0.97, 95% CI: 0.94, 0.999) and alcohol use disorders (OR: 0.96, 95% CI: 0.94, 0.99) were also related to a lower morning diurnal preference.

CONCLUSIONS

Our study provides evidence that being a morning person is a protective factor for various psychiatric disorders from a genetic perspective. The results provide insights for potential targeted interventions to improve mental wellbeing.

摘要

背景

早晨昼夜偏好与精神疾病之间的因果关系仍然不明。我们使用双向双样本孟德尔随机化(MR)方法,旨在探索早晨昼夜偏好与七种主要精神疾病之间的潜在因果关联。

方法

MR是一种遗传流行病学方法,利用基因变异作为工具变量来推断暴露因素与结果之间的因果关联。我们从全基因组关联研究(GWAS)数据集中获取早晨昼夜偏好数据,并将252,287人确定为早起者。精神疾病数据来自芬兰基因联盟R9数据集。我们的主要分析采用逆方差加权(IVW)方法,通过合并每个基因变异的估计值来评估总体因果效应。还进行了包括加权中位数、MR-Egger回归、加权模式和简单模式技术在内的额外分析,以确保结果的稳健性。

结果

成为早起者与多种精神疾病的患病几率降低有关,包括抑郁症或心境恶劣障碍(比值比:0.93,95%置信区间:0.88,0.999)、焦虑症(比值比:0.90,95%置信区间:0.84,0.96)、自我伤害行为(比值比:0.87,95%置信区间:0.76,0.99)、物质使用障碍(比值比:0.81,95%置信区间:0.71,0.93)、酒精依赖(比值比:0.82,95%置信区间:0.73,0.92)、酒精使用障碍(比值比:0.85,95%置信区间:0.76,0.94)、急性酒精中毒(比值比:0.86,95%置信区间:0.76,0.96)、精神分裂症(比值比:0.77,95%置信区间:0.65,0.92)以及精神分裂症或妄想症(比值比:0.80,95%置信区间:0.70,0.92)。酒精依赖(比值比:0.97,95%置信区间:0.94,0.999)和酒精使用障碍(比值比:0.96,95%置信区间:0.94,0.99)也与较低的早晨昼夜偏好有关。

结论

我们的研究提供了证据,表明从基因角度来看,成为早起者是预防各种精神疾病的一个保护因素。这些结果为改善心理健康的潜在靶向干预措施提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9256/11508865/962c37aca1f2/life-14-01225-g001.jpg

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