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Dr. María Soler, Dr. Josep Antoni Ramos Quiroga, Dr. Marta Ribasés
Understanding the genetics of ADHD and the association with other pathologies will help to prevent and diagnose patients early and facilitate research into new targeted therapies.
Attention deficit hyperactivity disorder (ADHD) is characterized by hyperactivity and impulsive and inattentive behaviors that make daily life difficult. It affects 5% of children, and may persist into adulthood in two out of three affected individuals. Its development depends on environmental and genetic factors, but it is genetics that has the greatest weight: it is estimated that it explains 74% of its variability. The journal Nature Genetics publishes the results of an international study, the largest to date, which has investigated possible genetic variants related to ADHD in order to understand in depth the genetics associated with this disorder. The work, led by the University of Aarhus in Denmark, has counted with the collaboration of the Vall d'Hebron Research Institute (VHIR), the CIBER of Mental Health (CIBERSAM), the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB), the Institut de Recerca Sant Joan de Déu (IRSJD) and the CIBERER of Rare Diseases (CIBERER).
The work has analyzed the genome of 28,691 patients with ADHD and 186,843 healthy people. This is double the number of samples studied compared to previous studies. "There are multiple genetic factors with small effects involved in ADHD and, therefore, it is necessary to study numerous cases to know in depth the biological basis of the disorder and the association with other pathologies", says Dr. Maria Soler, researcher of the Psychiatry, Mental Health and Addictions group of VHIR and CIBERSAM.
A genome-wide association study (GWAS) has investigated possible genetic variants, i.e. changes in the genome that increase the risk of ADHD, and assessed their impact on the development of the disorder.
The work has identified 27 regions of the genome associated with ADHD, 21 of which had not been described until now. Among these regions, 76 genes at increased risk have been prioritized, which are especially important during embryonic development and involved in cognitive skills. It is estimated that, among the genetic factors associated with ADHD, there are 7,000 common genetic variants, i.e. present in more than 1% of the population. Although this figure is high, the authors argue that it is lower than for other psychiatric disorders such as schizophrenia, autism or depression.
Among the genes identified, the authors highlight variants found in the SORCS3, FOXP1 and FOXP2 genes: "We knew about SORCS3 because of the impact that common variants of this gene have on the development of psychiatric disorders. For the first time, we confirm that there are rare variants (present in less than 1% of individuals) involved in ADHD", explains Dr. Marta Ribasés, researcher of the Psychiatry, Mental Health and Addictions group at VHIR and CIBERSAM.
On the other hand, the work shows, for the first time, that there are common genetic variants involved in ADHD that are related to the affectation of specific cognitive functions, such as attention, working memory or voluntary movement, all of them affected in patients with ADHD.
ADHD and the relationship with other psychiatric disorders
ADHD often presents with other psychiatric disorders. In this regard, the work identified that more than 90% of the variants associated with ADHD influence the development of schizophrenia and major depression, and 84% were related to autism spectrum disorder. In addition, 79% of the variants were found to be associated with poor school performance in children. "These results abound in the idea that many psychiatric disorders share genetic risk factors, and this would partly explain the high comorbidity that exists between them", explains Bru Cormand, director of the Department of Genetics, Microbiology and Statistics at the Universitat de Barcelona and member of IBUB, IRSJD and CIBERER.
"Understanding the genetics of ADHD and the association with other disorders will help to prevent and diagnose patients early. In addition, it facilitates the research of new targeted therapies", says Dr. Josep Antoni Ramos Quiroga, head of the Psychiatry Department at Vall d'Hebron University Hospital and of the Psychiatry, Mental Health and Addictions group at VHIR and CIBERSAM researcher.
More than 80% of the genetic variants with an effect on ADHD also influence the development of other psychiatric disorders, such as schizophrenia, major depression or autism spectrum disorder.
Psychiatrics, General Hospital
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