Quantitative and molecular genetics of ADHD

ADHD is a common and highly heritable disorder. Family, twin, and adoption studies confirm a strong genetic influence in risk for ADHD and there has been a great deal of interest in identifying the genetic factors involved. Quantitative genetic studies find that genetic risk for ADHD is continuously distributed throughout the population, that there are both shared and unique genetic influences on inattention and hyperactivity-impulsivity, and that ADHD shares genetic risk factors with commonly co-occurring clinical syndromes and traits. ADHD is found at all ages and the underlying genetic architecture is similar across the lifespan. In terms of specific genetic findings, there is consistent evidence of monoamine neurotransmitter involvement with the best evidence coming from genetic markers in or near the dopamine D4 and D5 receptor genes. Recent genome-wide association studies have identified new association findings, including genes involved in cell division, cell adhesion, neuronal migration, and neuronal plasticity. However, as yet, none of these pass genome-wide levels of significance. Finally, recent data confirm an important role for rare copy number variants, including those that are found in schizophrenia and autism. Future work should use genetic association data to determine the nature of the cognitive, neuronal and cellular processes that mediate genetic risks on behaviour, and identify environmental factors that interact with genetic risks for ADHD

The genetics of attention deficit/hyperactivity disorder in adults, a review

Item does not contain fulltextThe adult form of attention deficit/hyperactivity disorder (aADHD) has a prevalence of up to 5% and is the most severe long-term outcome of this common neurodevelopmental disorder. Family studies in clinical samples suggest an increased familial liability for aADHD compared with childhood ADHD (cADHD), whereas twin studies based on self-rated symptoms in adult population samples show moderate heritability estimates of 30-40%. However, using multiple sources of information, the heritability of clinically diagnosed aADHD and cADHD is very similar. Results of candidate gene as well as genome-wide molecular genetic studies in aADHD samples implicate some of the same genes involved in ADHD in children, although in some cases different alleles and different genes may be responsible for adult versus childhood ADHD. Linkage studies have been successful in identifying loci for aADHD and led to the identification of LPHN3 and CDH13 as novel genes associated with ADHD across the lifespan. In addition, studies of rare genetic variants have identified probable causative mutations for aADHD. Use of endophenotypes based on neuropsychology and neuroimaging, as well as next-generation genome analysis and improved statistical and bioinformatic analysis methods hold the promise of identifying additional genetic variants involved in disease etiology. Large, international collaborations have paved the way for well-powered studies. Progress in identifying aADHD risk genes may provide us with tools for the prediction of disease progression in the clinic and better treatment, and ultimately may help to prevent persistence of ADHD into adulthood