TY - JOUR
T1 - Investigating the genetic and causal relationship between initiation or use of alcohol, caffeine, cannabis and nicotine
AU - Chang, Lun-Hsien
AU - Ong, Jue-Sheng
AU - An, Jiyuan
AU - Verweij, Karin J. H.
AU - Vink, Jacqueline M.
AU - Pasman, Joëlle
AU - Liu, Mengzhen
AU - MacGregor, Stuart
AU - Cornelis, Marilyn C.
AU - Martin, Nicholas G.
AU - Derks, Eske M.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background: 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. Methods: 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 (h2) estimation for individual SU traits, followed by genetic correlation analyses and two-sample Mendelian randomisation (MR) studies between substance use trait pairs. Results: SNP h2 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. Conclusions: 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.
AB - Background: 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. Methods: 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 (h2) estimation for individual SU traits, followed by genetic correlation analyses and two-sample Mendelian randomisation (MR) studies between substance use trait pairs. Results: SNP h2 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. Conclusions: 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.
KW - Coffee
KW - Genetic instruments
KW - Single nucleotide polymorphism
KW - Substance use
KW - Tea
KW - Tobacco
KW - Two-sample Mendelian randomisation
UR - http://www.scopus.com/inward/record.url?scp=85082674146&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.drugalcdep.2020.107966
DO - https://doi.org/10.1016/j.drugalcdep.2020.107966
M3 - Article
C2 - 32276208
SN - 0376-8716
VL - 210
JO - Drug and alcohol dependence
JF - Drug and alcohol dependence
M1 - 107966
ER -