Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Addict Biol. 2021 Nov;26(6):e13030. doi: 10.1111/adb.13030. Epub 2021 Mar 17.
Cannabis use is associated with a number of psychiatric disorders; however, the causal nature of these associations has been difficult to establish. Mendelian randomization (MR) offers a way to infer causality between exposures with known genetic predictors (genome-wide significant single nucleotide polymorphisms [SNPs]) and outcomes of interest. MR has previously been applied to investigate the relationship between lifetime cannabis use (having ever used cannabis) and schizophrenia, depression, and attention deficit hyperactivity disorder (ADHD), but not bipolar disorder, representing a gap in the literature. We conducted a two-sample bidirectional MR study on the relationship between bipolar disorder and lifetime cannabis use. Genetic instruments (SNPs) were obtained from the summary statistics of recent large genome-wide association studies (GWAS). We conducted a two-sample bidirectional MR study on the relationship between bipolar disorder and lifetime cannabis use using inverse variance weighted regression, weighted median regression, and Egger regression. Genetic liability to bipolar disorder was significantly associated with an increased risk of lifetime cannabis use; however, genetic liability to lifetime cannabis use showed no association with the risk of bipolar disorder. The sensitivity analyses showed no evidence for pleiotropic effects. The present findings support a causal effect of liability to bipolar disorder on the risk of using cannabis at least once. No evidence was found for a causal effect of liability to cannabis use on the risk of bipolar disorder. These findings add important new knowledge to the understanding of the complex relationship between cannabis use and psychiatric disorders.
大麻使用与许多精神疾病有关；然而，这些关联的因果性质很难确定。孟德尔随机化（MR）提供了一种方法，可以推断具有已知遗传预测因子（全基因组显著单核苷酸多态性 [SNP]）的暴露与感兴趣的结果之间的因果关系。MR 先前已被应用于研究终生大麻使用（曾经使用过大麻）与精神分裂症、抑郁症和注意缺陷多动障碍（ADHD）之间的关系，但与双相情感障碍无关，这代表了文献中的一个空白。我们对双相情感障碍和终生大麻使用之间的关系进行了两样本双向 MR 研究。遗传工具（SNP）来自最近的大型全基因组关联研究（GWAS）的汇总统计数据。我们使用逆方差加权回归、加权中位数回归和 Egger 回归对双相情感障碍和终生大麻使用之间的关系进行了两样本双向 MR 研究。双相情感障碍的遗传易感性与终生大麻使用的风险增加显著相关；然而，终生大麻使用的遗传易感性与双相情感障碍的风险之间没有关联。敏感性分析没有发现多效性作用的证据。本研究结果支持双相情感障碍易感性对大麻使用风险（至少一次）的因果作用。没有证据表明大麻使用易感性对双相情感障碍风险有因果作用。这些发现为理解大麻使用和精神疾病之间复杂关系增添了重要的新知识。
