Externalizing Behaviors and mRNA expression of ST3GAL3 in adult ADHD
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2018-09-01
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en
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Objective: To study the associations between externalizing behaviors, mRNA ST3GAL3 expression of the ADHD risk variant rs11420276, and single CpG-methylation in adults with ADHD. Introduction: ADHD is a highly inheritable disorder (~76%), being demonstrated to persist into adulthood in up to 60% of affected individuals, with a broad variety of daily life impairments, many of them related to impulsive behaviors. Environmental influences can contribute to the etiology of the disorder through epigenetic modifications like DNA-methylation, generally altering gene expression. Method: Behavioral data from ADHD adults (n = 142) and healthy controls (n =141) was used to select variables measuring impulsivity and hyperactivity in the sample. ST3GAL3 mRNA expression analyses were performed using Taqman® assays in a subset of ADHD adults (n= 49) and healthy controls (n =45). ST3GAL3 single CpG site methylation data was available for ADHD adults (n =96) and healthy controls (n =92) from a previous study. Results: DIVA hyperactivity and impulsivity symptoms in childhood and Extraversion were significantly associated with mRNA ST3GAL3 expression. ST3GAL3 mRNA expression, was not differential between ADHD individuals and healthy controls, and our SNP of interest rs11420276 is not an eQTL for ST3GAL3 according to the results obtained. No significant associations were found between externalizing behaviors, mRNA ST3GAL3 expression and single CpG site methylation all together. Only the single CpG site 44172575 showed differential methylation between ADHD individuals and healthy controls, and associated significantly with ST3GAL3 mRNA expression. Conclusions: The variation in the mRNA expression of ST3GAL3 is hypothesized to related to the hyperactive component of ADHD disorder more than to the impulsive component in the sample studied. Variables robustly related to impulsivity in ADHD individuals did not associate significantly with the expression of ST3GAL3, meanwhile variables that have a link with motor activity in humans did. The results obtained overall are in line with the biological role of ST3GAL3.
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Faculteit der Sociale Wetenschappen