Introduction

Cannabis use disorder (CUD) and cannabis use (CU) are significant conditions frequently co-occurring with attention-deficit hyperactivity disorder (ADHD). A recent genome-wide association study (GWAS) has shed light on the genetic overlap between ADHD and these cannabis-related conditions. This article delves into the study’s findings, highlighting the genetic loci associated with these disorders and their implications for understanding the comorbidity of ADHD and CUD or CU.

Genetic Overlap Between ADHD and Cannabis Use Disorders

The GWAS identified 36 genome-wide significant loci that are concordant for both ADHD and CUD, and ten loci for ADHD and CU. One of the key risk genes identified for ADHD-CUD is DRD2. The study found that ADHD-CUD risk genes exhibited high expression levels across various brain tissues and developmental stages, a pattern not observed in ADHD-CU genes.

Genetic Correlations and Substance Use

ADHD-CUD and ADHD-CU demonstrated similar genetic correlations with substance use; however, they differed significantly when it came to substance-use disorders. This differentiation underscores the complexity of the genetic interplay between ADHD and cannabis-related disorders.

Polygenic Scores (PGS) and Psychiatric Disorders

Individuals with ADHD-CUD showed increased polygenic scores for psychiatric disorders compared to those with ADHD alone. Moreover, they also exhibited a higher burden of rare deleterious variants. These findings suggest that the genetic underpinnings of ADHD-CUD may contribute to a broader spectrum of psychiatric comorbidities.

Risk Stratification

The stratification of individuals with ADHD by their CUD PGS revealed stark differences in the risk of developing comorbid CUD. Those in the highest CUD-PGS bin faced an absolute risk of 22% for comorbid CUD, which is substantially higher than the 1.6% risk observed among control individuals without ADHD.

Sex-Specific Differences

The study also highlighted substantial sex-specific differences in the risk of CUD. Men in the highest CUD-PGS bin had an approximately 10% higher risk of developing CUD compared to women in the same genetic risk category.

Implications

These findings provide critical insights into the genetic factors contributing to the co-occurrence of ADHD and cannabis use disorders. Understanding these genetic overlaps can inform targeted interventions and personalised treatment strategies for individuals at high risk of developing these comorbid conditions.

Source: Nature