Genome-wide risk for persistent ADHD and its relationship with other behavioural or psychiatric abnormalities
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2020-12-15
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en
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Abstract
Background: Although ADHD is widely perceived as a disorder predominantly prevalent in children, the probability of functional impairment or subthreshold impairing symptoms persisting into adulthood is still quite high. The current study aims to investigate the underlying genetic patterns associated with ADHD, in particular with persistent ADHD and potential correlations between persistence of ADHD and other behavioural or psychiatric abnormalities.
Methods: We used four different GWAS summary statistics for our primary analyses: childhood ADHD, adulthood ADHD, a newly derived genome-wide factor reflecting polygenic risk for ADHD persistence, and a genome-wide factor for general psychopathology. We performed linkage disequilibrium score regression (LDSC) to test for genetic overlap between each of the four genomic risk signatures, used FUMA to identify molecular pathways involved in the genetic risk for persistent ADHD, and LD hub to conduct pairwise genetic correlations between the polygenic persistence factor and related phenotypes.
Results: LDSC analysis revealed strong significant positive correlations between all combinations of the four datasets, except for the persistence factor and childhood ADHD. We found tissue specificity of the polygenic persistence factor for the hippocampus, amygdala, and cortical areas such as frontal cortex and anterior cingulate cortex. Our findings also show genetic correlations between the polygenic persistence factor and depression, schizophrenia and rheumatoid arthritis. We also found nominal significant pathways such as “regulation of IFNα signalling” and “nerve development” associated with persistent ADHD.
Conclusion: We found evidence for genetic correlations of the polygenic persistence factor and psychopathological symptoms and disorders. Furthermore, our findings suggest common genetic risk patterns of persistent ADHD and inflammatory diseases such as rheumatoid arthritis. It may give way to a better assessment of the prognoses and helps to come to decisions in therapeutic questions as far as to establish new therapeutic strategies.
Keywords: ADHD, Persistent, Child, Adult, LDSC, Genetics, P-Factor, Neurodevelopmental Disorder, GWAS
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Faculteit der Sociale Wetenschappen