¹National Health Research Institutes, Center for Neuropsychiatric Research, Zhunan Town, Miaoli County, Taiwan, ²Taipei City Psychiatric Center, Taipei City Hospital, Department of Psychiatry, Taipei City, Taiwan

Background: There has been evidence that methamphetamine (METH) use disorder is heritable and probably highly polygenic. Shared genetic factors may explain the high comorbidity between METH use and other psychiatric disorders. Previous studies also suggest possible shared etiological mechanisms between METH-associated psychosis and primary psychosis.

Aims & Objectives: We aimed to examine whether METH use disorders are genetically correlated with other psychiatric disorders using a polygenic risk score (PRS) approach.

Method: A total of 1,227 patients with MA use were recruited. Genome-wide single nucleotide polymorphism (SNP) genotyping, demographic, and clinical information were obtained. Healthy controls were 111,913 individuals, who self-reported no history of psychiatric and neurologic disorders, with genome-wide genotypic data available from Taiwan Biobank. A genome-wide association analysis (GWAS) for METH users vs. healthy individuals was conducted. We used PRS-CSx to calculate PRS for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), alcohol dependence (AD), and cigarette smoking (CS), and tested their associations with METH use and METH-associated psychosis.

Results: The GWAS of METH use (n=113,130) identified a significant association with RAP1A gene in chromosome 1, in which the most significant SNP is rs7525578 (P=3.86E-42). METH use was significantly associated with PRS of SCZ (P= 0.0023), MDD (P= 0.0004), ADHD (P= 2.09E-16), AD (P= 1.62E-19), and CS (P= 7.58E-30). METH-associated psychosis was significantly associated with PRS of SCZ (P=0.0015).

Discussion & Conclusions: METH use was genetically correlated with SCZ, MDD, ADHD, AD, and CS, while METH-associated psychosis was genetically correlated with SCZ.