Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Aug 28:6:49.
doi: 10.1186/s13229-015-0041-0. eCollection 2015.

A comprehensive meta-analysis of common genetic variants in autism spectrum conditions

Varun Warrier #  1 , Vivienne Chee #  1 , Paula Smith  1 , Bhismadev Chakrabarti  1   2 , Simon Baron-Cohen  1   3
Affiliations

A comprehensive meta-analysis of common genetic variants in autism spectrum conditions

Varun Warrier et al. Mol Autism. .

Abstract

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, 8 of which had P values below a threshold of significance of 0.01. Of these 15 variants, 11 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.

Conclusions: 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.

Keywords: Association; Autism spectrum conditions; Genetic variants; Insertions; Meta-analysis.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Schematic diagram of meta-analysis protocol
See this image and copyright information in PMC

References

    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4. Washington, DC: American Psychiatric Association; 1994.
    1. Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The familial risk of autism. JAMA. 2014;311:1770–7. doi: 10.1001/jama.2014.4144. - DOI - PMC - PubMed
    1. Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, et al. Most genetic risk for autism resides with common variation. Nat Genet. 2014;46:881–5. doi: 10.1038/ng.3039. - DOI - PMC - PubMed
    1. Klei L, Sanders SJ, Murtha MT, Hus V, Lowe JK, Willsey AJ, Moreno-De-Luca D, et al. Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism. 2012;3:9. doi: 10.1186/2040-2392-3-9. - DOI - PMC - PubMed
    1. Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet. 2014;383:896–910. doi: 10.1016/S0140-6736(13)61539-1. - DOI - PubMed