A comprehensive meta-analysis of common genetic variants in Autism Spectrum Conditions
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Warrier, V., Chee, V., Smith, P., Chakrabarti, B., & Baron-Cohen, S. (2015). A comprehensive meta-analysis of common genetic variants in Autism Spectrum Conditions. Molecular Autism, 6 https://doi.org/10.1186/s13229-015-0041-0
Background: Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by difficulties in social interaction and communication alongside repetitive and stereotyped behaviours. ASC are heritable, and common genetic variants contribute substantial phenotypic variability. More than 600 genes have been implicated in ASC to date. However, a comprehensive investigation of candidate gene association studies in ASC is lacking. Methods: In this study, we systematically reviewed the literature for association studies for 552 genes associated with ASC. We identified 58 common genetic variants in 27 genes that have been investigated in three or more independent cohorts and conducted a meta-analysis for 55 of these variants. We investigated publication bias and sensitivity, and performed stratified analyses for a subset of these variants. Results: We identified 15 variants nominally significant for the mean effect size, eight of which had P values below a threshold of significance of 0.01. 11 of these 15 variants were re-investigated for effect sizes and significance in the larger Psychiatric Genomics Consortium dataset, and none of them were significant. Effect direction for 8 of the 11 variants were concordant between both the datasets, although the correlation between the effect sizes from the two datasets was poor and non-significant. Conclusion: This is the first study to comprehensively examine common variants in candidate genes for ASC through meta-analysis. While for majority of the variants, the total sample size was above 500 cases and 500 controls, the total sample size was not large enough to accurately identify common variants that contribute to the aetiology of ASC.
Meta-analysis, association, genetic variants, insertions, autism spectrum conditions
We are grateful to Dr Anitha Ayyappan Pillai, Prof. Elisabetta Trabetti and Dr. Wouter Staal for data-sharing. We thank Florina Uzefovsky for her critical comments and advice. This study was funded by grants from Target Autism Genome, the Autism Research Trust, Wellcome Trust Sanger Centre, and the Medical Research Council UK. VW is funded by the Nehru Trust for Cambridge University, St. John's College, and Cambridge Commonwealth Trusts. This study was submitted for the partial fulfilment of an MSc degree for VJC from Imperial College London, and a PhD degree for VW from the University of Cambridge.
External DOI: https://doi.org/10.1186/s13229-015-0041-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250336
Creative Commons Attribution 4.0
Licence URL: http://creativecommons.org/licenses/by/4.0/