Ragnheidur Fossdal1, Stacy Steinberg1, Pall Magnusson2, Bertrand Lauth2, Olafur O. Gudmundsson2, Stefan Hreidarsson3, Evald Saemundsen, PhD3, Gyda Bjornsdottir1, Hrefna Einarsdottir1, Hreinn Stefansson1, Jeffrey Gulcher1, Kristleifur Kristjansson1, Thorgeir E. Thorgeirsson1, and Kari Stefansson1. (1) deCODE genetics Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, (2) Department of Child and Adolescent Psychiatry, Landspitali University Hospital, Dalbraut 12, IS-105, Reykjavik, Iceland, (3) Division of Autism Spectrum Disorders, State Diagnostic and Counseling Center, Digranesvegur 5, 200 Kópavogur, Iceland
Background: A number of rare chromosomal events have been identified as causal factors for autism spectrum disorders. The genotyping of a large population sample provides increased power for the detection of new rare events associated with autism.
Objectives: This study aims at detecting de novo and transmitted CNV regions associated with autism in order to increase the specificity of other genetic analysis methods used to detect susceptibility variants.
Methods: A search for copy number variants conferring risk of autism was carried out through a population study of autistic individuals ascertained through the State Diagnostic Counseling Center and the Department of Child and Adolescent Psychiatry in Iceland. To identify and characterize de novo and transmitted CNVs associated with autism, a total of 27,436 Icelandic individuals genotyped at deCODE genetics for 317,503 SNPs using the HumanHap300 BeadChip (Illumina) were examined for increases and decreases in copy number using a Hidden Markov Model applied to normalized intensity data. The data set included 26,532 Icelandic controls, 334 probands and 570 parents of the autistic individuals.
Results: We identified more than 20 genomic regions containing large CNVs. Some of these regions were known to harbour CNVs previously identified in autistic individuals e.g. chromosome 1q, 2q, 15q, 16p, 17p and 22q. A few novel regions were detected. All regions were examined for association with autism in the Icelandic cohort.
Conclusions: Studies focusing on CNVs can find regions associated with autistic phenotypes increasing the specificity of other genetic analysis methods used to detect susceptibility variants.