Apr 24, 2020

Combining multivariate genomic approaches to elucidate the comorbidity between ASD and ADHD

BioRxiv : the Preprint Server for Biology
Hugo PeyreJ.-B. Pingault

Abstract

Background: Several lines of evidence point toward the presence of shared genetic factors underlying Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). However, Genome-Wide Association Studies (GWAS) have yet to identify risk variants (i.e. Single-Nucleotide Polymorphisms, SNPs) shared by ADHD and ASD. Methods: Two complementary multivariate analyses - genomic structural equation modelling (SEM) and colocalization analysis - were exploited to identify the shared SNPs for ASD and ADHD, using summary data from two independent GWAS of ASD (N=46,350) and ADHD individuals (N=55,374). Results: Genomic SEM identified 7 novel SNPs shared between ASD and ADHD (pgenome-wide<5e-8), including three SNPs that were not identified in any of the original univariate GWAS of ASD and ADHD (rs227378, rs2391769 and rs325506). We also mapped 4 novel genes (MANBA, DPYD, INSM1, and PAX1) to SNPs shared by ASD and ADHD, as well as 4 genes that had already been mapped to SNPs identified in either ASD or ADHD GWAS (SORCS3, XRN2, PTBP2 and NKX2-4). All the shared genes between ADHD and ASD were more prominently expressed in the brain than the genes mapped to SNPs specific to ASD or ADHD. Colocalization analyses revealed th...Continue Reading

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Mentioned in this Paper

Pongidae
CFC1 gene
Genome
Recombination, Genetic
Cranial Apex
Hominoidea
Genomics
CFC1 wt Allele
Local
Species

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