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Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis

By Victoria Powell, Joanna Martin, Anita Thapar, Frances Rice, Richard Anney

Posted 23 Apr 2020
bioRxiv DOI: 10.1101/2020.04.22.054908

Attention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p=5x10-8) SNPs in the meta-analysis that were also strongly associated (p=5x10-4) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were identified that were associated with each disorder separately (p=5x10-4) and in the cross-disorder meta-analysis (p=5x10-8). Nine of these SNPs had not been reported previously in either individual GWAS and can be considered as novel signals. Evidence supported nine of the fourteen SNPs acting as eQTL and two of the SNPs as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel regions of the genome that may be implicated in this overlap. ### Competing Interest Statement The authors have declared no competing interest.

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