ebook_ADHD2019

The World Federation of ADHD Guide 7 The genetic risk for ADHD was positively correlated with the genetic risk for co- ronary artery disease and lung cancer, which suggests that people with ADHD are at risk for these disorders. The ADHD risk score was positively correlated with having a large family and having children at a young age. These findings are consistent with longitudinal studies of the disorder. Higher genetic risk scores for ADHD also predicted a younger age of death of the respondent’s mother and father. This finding could be due to ADHD’s shared genetic risk for obesity and medical outcomes. Up to now, we have only been discussing common DNA variants, i.e., those that occur in more than one percent of the population. Our current thinking is that the genetic predisposition for most cases of ADHD is due to these many common va- riants that constitute the polygenic risk for the disorder. That said, researchers have also discovered rare variants that cause ADHD or symptoms of the disorder. The first information about rare variants came from studies of syndromic chromosomal anomalies such as velo-cardio facial syndrome fragile-X syndrome, Turner syndro- me, tuberous sclerosis, neurofibromatosis, Klinefelter syndrome, and Williams syn- drome. ADHD symptoms are frequently observed in patients with these conditions. Although GWAS had been developed to assay common variants, this method can also detect large, rare copy number variants (CNVs). CNVs delete or duplica- te a large section of DNA that might contain part of a single gene or several genes in their entirety. Because many of these create large genomic lesions, they seem to have clear consequences for gene functioning. Most studies of CNVs in ADHD have found an increased burden among patients with ADHD compared with con- trols. These data have been summarized fy Thapar et al., 11 who reported that dele- tions and duplications are equally over-represented in ADHD samples. The CNVs found in ADHD studies showed some overlap with the CNVs found in studies of schizophrenia and ASDs. Thapar et al. 11 further showed that ADHD CNVs affected genes in the following biological pathways: respiratory electron transport, organonitrogen compound catabolic process, transmembrane transporter activity, carbohydrate derivative catabolic process, ligand-gated ion channel activity, me- thyltransferase activity, transmembrane transport and ion gated channel activity. Another approach to rare variant discovery uses whole genome sequencing or whole exome sequencing. These methods are used to discover rare SNPs, which are called rare single nucleotide variants (SNVs). Because ADHD sequencing stu- dies are still in their infancy, it is too soon to draw firm conclusions about the role of SNVs in ADHD. For a recent review, see Faraone and Larsson. 4 SUMMARY: GENETIC CAUSES OF ADHD There can be no doubt now that people with ADHD carry DNA variants that ope- rate via unknown mechanisms to cause inattention, hyperactivity and impulsivity.