Because > 70% of persons with stimulant use disorder have comorbid alcohol or cannabis use disorders and more than one-third have anxiety disorder26, and amphetamine-related medications are used to treat attention deficit hyperactivity disorder (ADHD)27, we investigated the possibility of pleiotropy using GWAS summary statistics that were available in 2017 from the Psychiatric Genetics Consortium on LD Hub28 for ADHD (in a predominantly EA sample)29, alcohol dependence (in a trans-ancestral sample)30, and anxiety disorder (in an EA sample)31. Pleiotropy analyses were performed using a mixture model implemented in the Genetic Analysis Incorporating Pleiotropy and Annotation (GPA) software32. Parameters were estimated using GPA’s efficient expectation-maximization algorithm, wherein associated SNPs were modeled with a β [α, 1] distribution and unassociated SNPs with a uniform [0, 1] distribution. A likelihood ratio test was applied to determine the significance of pleiotropy between disorders based on an evaluation of the entire genome as well as individual SNPs.
