GIRK2 – A novel candidate gene for attention deficit hyperactivity disorder

Introduction: ADHD is a common, genetically complex disorder with high heritability. Previous studies depicted KCNJ6 (GIRK2) as a modulator of general synaptic functionality. We investigated the new candidate gene that is known to be involved in dopaminergic and serotonergic neurotransmission. Methods: The family-based sample includes 111 families of German origin with 165 affected children. For the case-control sample 400 affected adults and 300 healthy blood donors were recruited. Genotyping in both samples included variants located in the putative transcriptional control region, intron 1 and exons 3 and 4. In the family-based sample four additional SNPs located up to 10 kb in the putative promoter region were investigated. Results: We found a significant association between the promoter SNP and the SNP in intron 1 and ADHD in our family-based sample, endorsed by haplotype analysis. Statistical analysis of the four additional SNPs in the putative promoter region as well as in the case-control sample is in process. Discussion: We found evidence for association between ADHD and two SNPs of GIRK2, known to be involved in dopaminergic and serotonergic neurotransmission. Haplotype analysis showed an even stronger association with ADHD, further analysis is in process. To confirm functional relevance of these genetic variants structural analysis of the putative promoter regions and impact of the single polymorphisms on gene expression is currently in process.