Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia.
Statistical Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia.
Drug Alcohol Depend. 2020 May 1;210:107966. doi: 10.1016/j.drugalcdep.2020.107966. Epub 2020 Mar 20.
Caffeine, alcohol, nicotine and cannabis are commonly used psychoactive substances. While the use of these substances has been previously shown to be genetically correlated, causality between these substance use traits remains unclear. We aimed to revisit the genetic relationships among different measures of SU using genome-wide association study (GWAS) summary statistics from the UK Biobank, International Cannabis Consortium, and GWAS & Sequencing Consortium of Alcohol and Nicotine use.
We obtained GWAS summary statistics from the aforementioned consortia for ten substance use traits including various measures of alcohol consumption, caffeine consumption, cannabis initiation and smoking behaviours. We then conducted SNP-heritability (h) estimation for individual SU traits, followed by genetic correlation analyses and two-sample Mendelian randomisation (MR) studies between substance use trait pairs.
SNP h of the ten traits ranged from 0.03 to 0.11. After multiple testing correction, 29 of the 45 trait pairs showed evidence of being genetically correlated. MR analyses revealed that most SU traits were not causally associated with each other. However, we found evidence for an MR association between regular smoking initiation and caffeine consumption 40.17 mg; 95 % CI: [24.01, 56.33] increase in caffeine intake per doubling of odds in smoking initiation). Our findings were robust against horizontal pleiotropy, SNP-outliers, and the direction of causality was consistent in all MR analyses.
Most of the substance traits were genetically correlated but there is little evidence to establish causality apart from the relationship between smoking initiation and caffeine consumption.
咖啡因、酒精、尼古丁和大麻是常见的精神活性物质。虽然这些物质的使用先前已被证明与遗传有关，但这些物质使用特征之间的因果关系仍不清楚。我们旨在使用来自英国生物库、国际大麻联盟以及酒精和尼古丁使用的 GWAS 和测序联盟的全基因组关联研究（GWAS）汇总统计数据，重新研究不同的物质使用特征之间的遗传关系。
我们从上述联盟获得了十个物质使用特征的 GWAS 汇总统计数据，包括各种饮酒、咖啡因摄入、大麻起始和吸烟行为的测量。然后，我们对个体物质使用特征进行 SNP 遗传力（h）估计，然后进行遗传相关性分析和两个样本孟德尔随机化（MR）研究物质使用特征对。
十个特征的 SNP h 值范围从 0.03 到 0.11。在多重检验校正后，45 个特征对中有 29 对显示出遗传相关的证据。MR 分析表明，大多数物质使用特征彼此之间没有因果关系。然而，我们发现有证据表明，定期吸烟起始与咖啡因摄入之间存在 MR 关联，每增加一倍的吸烟起始几率，咖啡因摄入量增加 40.17 毫克；95%CI：[24.01, 56.33]。我们的发现对水平多效性、SNP 异常值具有稳健性，并且在所有 MR 分析中因果关系的方向都是一致的。
大多数物质特征在遗传上是相关的，但除了吸烟起始和咖啡因摄入之间的关系外，几乎没有证据可以确定因果关系。
