Influence of Candidate Genes on Attention Problems in Children: A Longitudinal Study

Abstract

Attention problems form one of the core characteristics of Attention-Deficit Hyperactive Disorder (ADHD), a multifactorial neurodevelopmental disorder. From twin research it is clear that genes play a considerable role in the etiology and in the stability of ADHD in childhood. Association studies have focused on genes involved in the dopaminergic and serotoninergic systems, but with inconclusive results. This study investigated the effect of 26 Single Nucleotide Polymorphisms (SNPs) in genes encoding for serotonin receptors 2A (HTR2A), Catechol-O-Methyltransferase (COMT), Tryptophane Hydroxylase type 2 (TPH2), and Brain Derived Neurotrophic Factor (BDNF). Attention problems (AP) were assessed by parental report at ages 3, 7, 10, and 12 years in more than 16,000 twin pairs. There were 1148 genotyped children with AP data. We developed a longitudinal framework to test the genetic association effect. Based on all phenotypic data, a longitudinal model was formulated with one latent factor loading on all AP measures over time. The broad heritability for the AP latent factor was 82%, and the latent factor explained around 55% of the total phenotypic variance. The association of SNPs with AP was then modeled at the level of this factor. None of the SNPs showed a significant association with AP. The lowest p-value was found for the rs6265 SNP in the BDNF gene (p = 0.035). Overall, our results suggest no evidence for a role of these genes in childhood AP.

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

“…These findings suggested that both BDNF polymorphisms could play a role in the etiology of ADHD [269]. From another perspective, van Beijsterveldt et al [270] have developed a parental-assessment report at ages 3, 7, 10, and 12 years over more than 16,000 twin pairs that 1148 genotyped children presenting attention disorder, a cornerstone of ADHD. They developed a longitudinal framework to test genetic association effects with 26 SNPs of genes encoding for several putative contributors to ADHD, including HTR2A, COMT, TPH2, and BDNF.…”

Is the child ‘father of the Man’? Evaluating the stability of genetic influences across development

“…Finally, two studies from a Dutch longitudinal sample assessed from childhood through to adolescence tested whether several serotonin and dopamine system‐related genes, including TPH2 and genes encoding serotonin transporters, were associated with longitudinal measures of attention problems, and anxiety and depression, respectively (Middeldorp, Slof‐Op’t Landt, Medland, van Beijsterveldt, Bartels, Willemsen, Hottenga, de Geus, Suchiman, Dolan, Neale, Slagboom & Boomsma, 2010; van Beijsterveldt, Middeldorp, Slof‐Op’t Landt, Bartels, Hottenga, Suchiman, Slagboom & Boomsma, 2011). Perhaps surprisingly, however, these longitudinal behavioral traits did not show an association with the selected candidate genes.…”

Incorporating Polygenic Risk Scores in the ACE Twin Model to Estimate A–C Covariance

“…Neale et al ( 2000 ) partitioned variation in serum APOE levels into that associated with the APOE locus and residual genetic variance. In a study of attention problems, van Beijsterveldt et al ( 2011 ) incorporated measured candidate gene information on SNPs in the serotonergic, dopaminergic system and the BDNF gene. The effect of SNPs was tested on a latent factor that summarized multiple assessments of attention problems across childhood.…”