Leveraging Polygenic Risk Scores to Advance Autism Epidemiology

The expansion in 2018 of GWAS data on persons with autism, through the iPSYCH and Psychiatric Genetics Consortium, has finally resulted in a sufficiently powered sample size (n=46,350) to detect common variants associated with ASD. These precise SNP-based association effect estimates enable derivation of a polygenic risk score (PRS), which captures the overall burden of genetic susceptibility to ASD (ASD-PRS). Quantitative PRS measures of individual genetic liability can serve as powerful tools to address pressing questions in autism research across a wide-range of settings. This panel will showcase the use of PRS to gain insights into ASD. First, we show that the iPSYCH-PGC PRS, discovered in a predominantly European sample, also associates with ASD case status in a racially and ethnically diverse US-based epidemiology sample (Benke; SEED sample). Second, we use PRS to determine the contribution of common variants to phenotypic variation in quantitative autistic traits among a clinically ascertained familial sample (Constantino; AGRE sample). Third, we compare PRS-based measures of ASD risk to psychiatric family history-based ASD risk (Schendel; Danish iPSYCH sample). Fourth, we use PRS concepts to provide insights into ASD subphenotypes (Grove; Danish iPSYCH sample). Our discussant will summarize emerging themes and future directions in ASD-PRS research.
Saturday, May 4, 2019: 10:30 AM-12:30 PM
Room: 517B (Palais des congres de Montreal)
Panel Chair:
D. Schendel
C. Ladd-Acosta
10:30 AM
Polygenic Risk for Autism Spectrum Disorder in the Study to Explore Early Development
K. S. Benke C. Ladd-Acosta C. J. Newschaffer M. D. Fallin L. A. Croen L. Schieve J. Daniels A. M. Reynolds D. Schendel
10:55 AM
Common Variant Burden Contributes to the Familial Aggregation of Quantitative Autistic Traits
J. N. Constantino R. E. Wagner W. Howells M. Panther J. Lowe D. Geschwind
11:20 AM
Polygenic Risk Score and Psychiatric Family History in Autism Spectrum Disorder
D. Schendel T. Laursen C. Ladd-Acosta M. D. Fallin B. K. Lee K. S. Benke J. Grove B. Vilhjalmsson A. Kalkbrenner C. B. Pedersen L. Ejlskov P. Mortensen A. Bøglum O. Mors T. Werge M. Nordentoft D. Hougaard E. Agerbo
11:45 AM
Polygenic Heterogeneity in Autism and in Related Phenotypes
J. Grove .. The iPSYCH-Broad/MGH Autism Working Group