Genome-wide association meta-anaylsis of autistic traits Aim of the project Autism is highly heritable, with twin and family-based heritability estimates between 64-92%. Recent estimates suggest that between 400 - 1000 genes may be involved, and that between 10-30% of autistic people can have rare genetic variants. Whole exome sequencing (WES) has identified specific clinical and behavioural phenotypes of autism attributable to variants in specific genes (e.g., CHD8, ADNP, and PTEN), whereas emerging evidence from GWAS of autistic traits suggest that autism is caused by variations in at least two different sources. Currently 78 genes, 11 CNVs, and 5 SNPs have been associated with high confidence with autism. While considerable progress has been made in rare-variant discovery for autism to date only 5 genome-wide significant loci for common variants have been identified for autism. This project will measure autistic traits in the general population and correlate common variations in the genome, thereby accelerating gene-discovery for autism. Using data from the UK Biobank, the Lifelines cohort, and other international collaborators, researchers will conduct the GWAS using multiple cohorts and different measures of autistic traits. The Autism Spectrum Quotient will be used to focus on autistic traits rather than autism so as to phenotype the general population and thus increase sample size and statistical power. Using data from the UK Biobank, the Lifelines cohort, and other international collaborators, researchers will conduct the GWAS using multiple cohorts and different measures of autistic traits. The short version of the Autism Spectrum Quotient (AQ-10) will be used to focus on autistic traits rather than autism so as to phenotype the general population and thus increase sample size and statistical power. Importance of research This study will accelerate gene discovery for autism by prioritising candidates for functional follow up; identify genes, pathways, and tissues for repurposing drug targets; provide the best-powered polygenic scores for autistic traits; and allow for integrated analyses using neuroimaging and other modalities in the UK Biobank. This will considerably further our understanding of autism biology, and will provide steps to subgroup individuals within the autism spectrum based on genetic variants, and help improve diagnosis by integrating genetic information with clinical and psychometric evaluation. Researchers involved Varun Warrier Key findings The project will run for two years from December 2018, with the GWAS being conducted in July 2019 or when N = 280,000.