ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Rommelse NN, 2008 (a)18726986
Citation	Rommelse N. N., Altink M. E., Arias-Vasquez A., Buschgens C. J., Fliers E., Faraone S. V., Buitelaar J. K., Sergeant J. A., Oosterlaan J. and Franke B. (2008) "Differential association between MAOA, ADHD and neuropsychological functioning in boys and girls." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1524-30.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	265 boys with ADHD, 89 male non-affected siblings, 85 girls with ADHD, and 106 female non-affected siblings
Predominant Ethnicity	Caucasian
Population	the Netherlands
Gender	265 boys, 85 girls
Age Group	Children/Adolescents : 5-19 years

Detail Info

Summary	The current study set out to examine the relationship between MAOA, ADHD, and neuropsychological functioning in both boys (265 boys with ADHD and 89 male non-affected siblings) and girls (85 girls with ADHD and 106 female non-affected siblings). A haplotype was used based on three single nucleotide polymorphisms (SNPs) (rs12843268, rs3027400, and rs1137070). Two haplotypes (GGC and ATT) captured 97% of the genetic variance in the investigated MAOA SNPs. The ATT haplotype was more common in non-affected siblings (P-value=0.025), conferring a protective effect for ADHD in both boys and girls. The target and direction of the MAOA effect on neuropsychological functioning was different in boys and girls: The ATT haplotype was associated with poorer motor control in boys (P-value=0.002), but with better visuo-spatial working memory in girls (P-value=0.01). These findings suggest that the genetic and neuropsychological mechanisms underlying ADHD may be different in boys and girls and underline the importance of taking into account sex effects when studying ADHD.
Total Sample	Families with at least one child with the combined subtype of ADHD (proband) and at least one additional sibling (regardless of possible ADHD-status) participated. For the current study, the sample was split by sex, resulting in the participation of 265 boys with ADHD, 89 male non-affected siblings, 85 girls with ADHD, and 106 female non-affected siblings. All children were between the ages of 5 and 19 years and were of European Caucasian descent.
Sample Collection	European Caucasian descent
Diagnosis Description	The screening procedures and measures for phenotyping have been described previously [Brookes et al., 2006]. Briefly, the diagnosis of ADHD was based on screening questionnaires (parent and teacher Conners' long version rating scales and parent and teacher Strengths and Difficulties Questionnaires [SDQ]) and a semi-structured interview.
Technique	An elaborate description of methods for DNA extraction is provided elsewhere [Brookes et al., 2006]. Briefly, DNA was extracted directly from blood samples or cell lines at Rutgers Cell line and DNA repository in the US. Three SNPs in MAOA (rs12843268 [intron 5, G/A], rs3027400 [intron 9, G/T] and rs1801291 [exon 14, now known as rs1137070, C/T]) were selected as these had shown nominal association with ADHD in a larger sample of IMAGE, in which the entire MAOA gene-region had been investigated using tagSNPs. The SNPswere genotyped using the Illumina Golden Gate AssayTM. Additional families, which had been included in IMAGE at a later stage and had not been described in the paper by Brookes et al., were genotyped for the three SNPs using ABI SNPlex as part of a replication study.
Analysis Method	Haplotype frequency was compared between the group of affected and non-affected participants in order to find differences in frequency distribution. The association of MAOA with the neuropsychological measures was analyzed using a linear mixed model with MAOA as factor and family structure as random effect. Correction for multiple comparisons according to the False Discovery Rate (FDR) controlling procedure was applied to the analyses with a Q-value setting of 0.05.
Result Description	The ATT haplotype was more common in non-affected siblings (P-value=0.025), conferring a protective effect for ADHD in both boys and girls. The target and direction of the MAOA effect on neuropsychological functioning was different in boys and girls: The ATT haplotype was associated with poorer motor control in boys (P-value=0.002), but with better visuo-spatial working memory in girls (P-value=0.01).

Genes reported by this study (count: 1)