SU16: THE IMPACT OF CNVs ON ASD/ADHD RISK IN MULTIPLEX FAMILIES

Abstract

Background Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) often co-occur within the same individual and/or family. High rates of heritability are characteristic of both ASD (90%) and ADHD (76%), indicating a strong genetic component. Family studies in clinical samples suggest 50–70% shared genetic risk factors among them. To date few large and rare Copy Number Variants (CNVs) have been associated with ASD and implicated in ADHD. Several overlapping findings indicate pleiotropic genes and shared biological pathways. In particular family studies are ideal for identification of segregating genetic variants such as CNVs and study their effect upon inherited traits. The aim of the study is to assess the impact of CNVs on ASD /ADHD risk in multiplex families. Methods ASD/ADHD patients, affected and unaffected relatives were recruited from a Psychiatric Outpatient Clinic (POC) in Denmark. For all participants psychiatric data was retrieved from the Danish National Health Registers and diagnostic data of ASD/ADHD patients was collected from the medical journals at POC. Blood or saliva sample was collected from all participants. Genotyping was performed on the ‘HumanOmniExpress-12v1-H’ microarray and OmniExpress-24 v1.2 BeadChip at deCODE Genetics (Reykjavik, Iceland) and at the Infinium PsychChip v1.0 array at Statens Serum Institute (Copenhagen, Denmark). CNVs were detected by the means of iPsychCNV and PennCNV. Results In total 39 families were recruited including 277 participants, among them 55 ASD/ADHD patients, 116 affected relatives and 99 unaffected relatives. The genetic analysis is ongoing. From the preliminary results, we observe a higher burden of large and rare CNVs in ASD/ADHD patients than affected relatives and unaffected relatives. Among patients CNVs are more frequent in ASD and co-morbid ASD+ADHD patients than in ADHD patients. Previous ASD and ADHD risk loci were identified, several of them segregating among affected and unaffected relatives. Discussion Our findings are consistent with others in the demonstration that large and rare CNVs are more likely to occur in patients, than unaffected relatives and in general show a stronger association to ASD than to ADHD. Furthermore, our findings support the fact that other genetic factors contribute to the inherited risk of ASD/ADHD.