No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder
Abstract
The Autism Genome Project (AGP) Consortium recently reported genome‐wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case–control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non‐centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case–control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta‐analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944–1.133), with a P‐value of 0.5 for ASD and OR of 0.99 (95% CI 0.88–1.11) with P‐value = 0.85 for the Autism (A) sub‐group. Therefore, this study does not provide support for the reported association between rs4141463 and autism. © 2011 Wiley‐Liss, Inc.
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If SNPs in MACROD2 or its intra-genic antisense RNA genes play a role in risk for ASD, their effect size is modest.
“If they do, however, there can now be little doubt that their effect size is modest on the basis of our results and others (24).”
From Individual common variants exert weak effects on the risk for autism spectrum disorders (2012) · cites this paper as [24]
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- Authors
- Curran, S., Bolton, P., Rozsnyai, K., Chiocchetti, A., Klauck, S. M., Duketis, E., Poustka, F., Schlitt, S., Freitag, C. M., Lee, I., Muglia, P., on behalf of the, I. T. A. N., Poot, M., Staal, W., de Jonge, M. V., Ophoff, R. A., Lewis, C., Skuse, D., Mandy, W., Vassos, E., Fossdal, R., Magnusson, P., Hreidarsson, S., Saemundsen, E., Stefansson, H., Stefansson, K., & Collier, D.
- Affiliations
- King's College London (GB)
- German Cancer Research Center (DE)
- Goethe University Frankfurt (DE)
- Saarland University (DE)
- University College London (GB)
- University of Toronto (CA)
- University Medical Center Utrecht (NL)
- deCODE Genetics (Iceland) (IS)
- Corresponding author
- Curran, Sarah
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2011-06-08
- Volume
- 156
- Issue
- 6
- Pages
- 633-639
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2140661418
- Cited by
- 34
- References
- 44
- Citations by year
- 2022: 1 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 1 · 2012: 5
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0510-10268)
- Medical Research Council
- National Institute of Mental Health (R01MH071425, MH071425)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- autism spectrum disorder, MACROD2, single nucleotide polymorphisms, genetic association, replication study
- MeSH terms
- Autistic Disorder, Europe, Genotype, Humans, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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