Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder

Abstract

As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

DNA methylation of GFI1 as a mediator of the association between prenatal smoking exposure and ADHD symptoms at 6 years: the Hokkaido Study on Environment and Children’s Health

“…ESR1, one of two ESR subtypes, is a nuclear receptor that is activated by the sex hormone estrogen. Single nucleotide polymorphisms within the ESR1 gene are associated with neuropsychiatric disorders including ADHD [ 33 , 34 ]. According to animal studies, prenatal exposure to chemicals such as phthalates and benzophenone-3 impairs neurodevelopment via disruption of Esr expression and alteration of the epigenetic status [ 35 , 36 ].…”

Autism spectrum disorder polygenic scores are associated with every day executive function in children admitted for clinical assessment

“…In a GWAS study, Sun et al found that ADHD children had genetic variants related to behavioral regulation impairments measured with the BRIEF [Sun et al, ]. In children with NDs such as ASD and ADHD, there are indications that BRI from the BRIEF is more strongly associated with genetic factors than the metacognitive aspects of executive function [Sun et al, ].…”

“…Dajani et al [] studied a sample of ASD, ADHD, or comorbid ASD and ADHD, and found that executive function performance did not match the diagnostic categories. Sun et al [] argue that is it more important to evaluate executive function than diagnosis for targeting executive function interventions. Taken together, this suggests that the Low and High PGS groups are not only an indirect measurement of ASD, but rather reflect that polygenic disposition for ASD associated with the behavior regulation part of executive function.…”

Neurodevelopmental Disorders, Glycemic Control, and Diabetic Complications in Type 1 Diabetes: a Nationwide Cohort Study

“…Lifetime diagnoses of neurodevelopmental disorders were identified from 5 registries: the National Patient Register (NPR) ( 20 ), the Clinical databases for Child and Adolescent Mental Health Services ( 21 ), the Habilitation Register ( 21 ) and the Halmstad University Register on Pupils with Intellectual Disability ( 22 ), and the Swedish Prescribed Drug Register ( 23 ). Diagnoses were defined in accordance with ICD codes for ASD (ICD-9: 299A, 299.8; ICD-10: F84.0, F84.1, F84.5, F84.8, F84.9) and intellectual disability (ICD-8: 310-315; ICD-9: 317-319; ICD-10: F70-F79).…”