Periodic Reporting for period 1 - GRASAD (Uncovering the genetic roots of ASD and ADHD)
Periodo di rendicontazione: 2020-09-01 al 2022-08-31
Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are common neurodevelopmental and childhood-onset chronic disorders. Despite being notably impairing and presenting deleterious effects on reproductive success they both are highly prevalent. Although they have distinct diagnostic definitions, they can co-occur in the same individual and they present a substantial overlap of symptoms. One of the hypotheses explaining the co-occurrence between ASD and ADHD proposes that they may have, at least in part, a common aetiology, which is supported by recent genetic studies.
The goal of GRASAD was to study two important and still unsolved issues regarding the genetic underpinnings of ASD and ADHD. On one side, this project aimed at understanding how a diverse set of genetic risk factors are involved in both ASD and ADHD and ultimately to specific symptoms shared between the two disorders. On the other side, we also aimed to study evolutionary aspects of the genetic roots of ASD.
In disorders such as ASD and ADHD, in which the set of genes involved has been estimated to be large and heterogeneous, it is crucial to identify risk genes that cut across disorders and may be relevant to specific disease symptoms. This is essential for the development of improved diagnostic procedures, to gain insight into the prognosis of the disorder and also for the development of new and effective pharmacological treatments. Moreover, studying these disorders from an evolutionary perspective can provide a more natural view of the disorder and help to understand why they are so prevalent today.
The goal of GRASAD was to study two important and still unsolved issues regarding the genetic underpinnings of ASD and ADHD. On one side, this project aimed at understanding how a diverse set of genetic risk factors are involved in both ASD and ADHD and ultimately to specific symptoms shared between the two disorders. On the other side, we also aimed to study evolutionary aspects of the genetic roots of ASD.
In disorders such as ASD and ADHD, in which the set of genes involved has been estimated to be large and heterogeneous, it is crucial to identify risk genes that cut across disorders and may be relevant to specific disease symptoms. This is essential for the development of improved diagnostic procedures, to gain insight into the prognosis of the disorder and also for the development of new and effective pharmacological treatments. Moreover, studying these disorders from an evolutionary perspective can provide a more natural view of the disorder and help to understand why they are so prevalent today.
In this project we have investigated the shared genetic bases of ASD and ADHD using different approaches. First, we studied the cumulative effect of ASD risk genetic variants on ADHD, which would help to understand the shared genetic bases between the two disorders. We have also explored the cumulative effect of both ASD risk variants and genetic risk variants shared between ASD and ADHD on specific symptoms of ADHD, such as inattention or hyperactivity/impulsivity, which also occur in patients with ASD. Our results turned to be negative, not being able to see any association between ASD genetic variants and ADHD clinical diagnosis or symptoms. Second, we wrote a review article on the state-of-the-art knowledge about the shared genetics between ADHD and several of its comorbidities, including ASD. This review provides a comprehensive overview of what is known from the literature and also from still unpublished works currently under way in the context of the Psychiatric Genomics Consortium (PGC). Finally, evolutionary analyses combining genomic data from Neanderthals (Homo neanderthalensis) and Homo sapiens, modern and ancient, are still in progress.
Our results on the shared genetic underpinnings of ASD and ADHD, although negative, are very valuable in the field of psychiatric genetics. As far as we know, this is the first study that has combined genetic data from ASD and ADHD to investigate whether common variation may explain differences in the severity of symptoms presented by patients. Understanding the genetic bases of specific symptoms in individuals with a psychiatric disorder is still an underexplored topic. In this sense, our results highlight the importance of deep phenotyping of symptom domains in psychiatric patients and it also highlights the pertinence of pursuing new approaches that allow identification of genetic variants explaining the differences in the symptoms that patients present, which often cut across disorders.