Association of norepinephrine transporter (NET, SLC6A2) genotype with ADHD-related phenotypes: findings of a longitudinal study from birth to adolescence

Psychiatry Res. 2015 Apr 30;226(2-3):425-33. doi: 10.1016/j.psychres.2014.12.029. Epub 2014 Dec 27.

Abstract

Variation in the gene encoding for the norepinephrine transporter (NET, SLC6A2) has repeatedly been linked with ADHD, although there is some inconsistency regarding the association with specific genes. The variants for which most consistent association has been found are the NET variants rs3785157 and rs28386840. Here, we tested for their association with ADHD diagnosis and ADHD-related phenotypes during development in a longitudinal German community sample. Children were followed from age 4 to age 15, using diagnostic interviews to assess ADHD. Between the ages of 8 and 15 years, the Child Behavior Checklist (CBCL) was administered to the primary caregivers. The continuous performance task (CPT) was performed at age 15. Controlling for possible confounders, we found that homozygous carriers of the major A allele of the functional promoter variant rs28386840 displayed a higher rate of ADHD lifetime diagnosis. Moreover, homozygous carriers of the minor T allele of rs3785157 were more likely to develop ADHD and showed higher scores on the CBCL externalizing behavior scales. Additionally, we found that individuals heterozygous for rs3785157 made fewer omission errors in the CPT than homozygotes. This is the first longitudinal study to report associations between specific NET variants and ADHD-related phenotypes during the course of development.

Keywords: Attention-deficit/hyperactivity disorder; Continuous performance task; Genetic association; Molecular heterosis; Norepinephrine transporter; Polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Child
  • Child, Preschool
  • Female
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Norepinephrine Plasma Membrane Transport Proteins / genetics*
  • Phenotype

Substances

  • Norepinephrine Plasma Membrane Transport Proteins
  • SLC6A2 protein, human