Genome-wide association studies in ADHD
background adhd is a common and highly heritable neuropsychiatric disorder that is seen in children and adults. Although heritability is estimated at around 76%, it has been hard to find genes underlying the disorder. adhd is a multifactorial disorder, in which many genes, all with a small effect, are thought to cause the disorder in the presence of unfavorable environmental conditions in most patients. Although whole genome linkage analyses and candidate gene-based association studies have been able to explain a part of the genetic contribution to disease, the largest part of the genes involved still needs to be identified.
aim To review recent gwas studies in adhd, and discuss their implications.
method Systematic review of published molecular-genetic papers in adhd.
results Though not genome-wide significant, findings from the individual studies converge to paint an interesting picture: suggestions are found for involvement of different neurotransmission and cell-cell communication systems. A potential involvement of potassium channel subunits and regulators warrants further investigation. More basic processes also seem important in adhd, especially neurite outgrowth, but also neuronal migration and neuronal plasticity as well as cell division and transcription. In conclusion, the gwas performed so far in adhd, though far from conclusive, provide a first glimpse at genes for the disorder. In addition, genome-wide studies investigating the role of oligogenic or even monogenic forms of adhd in the form of copy number variations (Wiliams e.a. 2010) identify additional genes of interest.
conclusion adhd seems to be in most cases a multifactorial disorder, but in some cases it is an oligogenic or even monogenic disorder. Molecular-genetic findings point to new interesting candidate genes that affect very basic cellular and molecular processes.