ASSOCIATIONS BETWEEN GENETIC LIABILITY TO ATTENTION DEFICIT HYPERACTIVITY DISORDER AND METHAMPHETAMINE ABUSE

Abstract Background Attention deficit hyperactivity disorder (ADHD) and substance use disorder co-occurs frequently. Both methamphetamine abuse and ADHD is heritable and probably highly polygenic. Shared genetic factors may explain the high comorbidity between methamphetamine abuse and ADHD. In this study, we hypothesize methamphetamine abuse may be genetically correlated with ADHD. Aims & Objectives The aim of the study was to examine the association of common genetic variants (i.e., single nucleotide polymorphisms [SNPs]) across the whole genome with methamphetamine abuse and to examine the genetic overlap between ADHD and methamphetamine abuse as well as other methamphetamine use variables. Method 143 treatment-seeking patients with methamphetamine abuse were recruited in Taipei City Hospital and 77,520 healthy individuals were Taiwan Biobank’ s participants with no prior history of psychiatric or substance use disorders. Genome-wide single nucleotide polymorphism genotyping, demographics, and clinical information were obtained. We conducted an exploratory genome-wide association analysis (GWAS) for methamphetamine abuse vs. healthy individuals. ADHD GWAS summary statistics from Psychiatric Genomics Consortium were utilized as the discovery datasets to compute a polygenic risk score (PRS) of ADHD for each subject in our study sample. We also examined the relationship between ADHD-PRS and methamphetamine use characteristics among the patients with methamphetamine abuse. Results Preliminary genome wide analysis revealed a significant SNP rs66510859 on chromosome 7 (P-value= 2.04E-09) associated with methamphetamine abuse. Methamphetamine abuse was significantly associated with ADHD-PRS with a P-value threshold of 0.05. ADHD-PRS with P-value threshold of 0.5 was associated with log-transformed earlier age of first use (beta=-6.1, p=0.02) and log-transformed regular use (beta=-6.0, p=0.01) after adjustment for covariates. Discussion & Conclusion Methamphetamine abuse may be genetically correlated with ADHD. Further study will examine the causal relationships between the genetic liability to ADHD, the Adult ADHD Self-Report Scale score, and clinical characteristics of methamphetamine abuse by using causal mediation analysis and Mendelian randomization.