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

Powell, Victoria, Martin, Joanna ORCID: https://orcid.org/0000-0002-8911-3479, Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X, Rice, Frances ORCID: https://orcid.org/0000-0002-9484-1729 and Anney, Richard ORCID: https://orcid.org/0000-0002-6083-407X 2021. Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: a GWAS meta-analysis. Scientific Reports 11 , 7353. 10.1038/s41598-021-86802-1

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Abstract

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 < 5 × 10–8) SNPs in the meta-analysis that were also strongly associated (p < 5 × 10–4) 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 associated with each disorder separately (p < 5 × 10–4) and in the cross-disorder meta-analysis (p < 5 × 10–8). Nine of these SNPs had not been highlighted previously in either individual GWAS. Evidence supported nine of the fourteen SNPs acting as eQTL and two 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 genomic regions that may be implicated in this overlap.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Nature Publishing Group
ISSN:	2045-2322
Funders:	MRC
Date of First Compliant Deposit:	24 March 2021
Date of Acceptance:	19 March 2021
Last Modified:	04 May 2023 19:38
URI:	https://orca.cardiff.ac.uk/id/eprint/140062

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