No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder

Sarah Curran, Patrick Bolton, Kinga Rozsnyai, Andreas Chiocchetti, Sabine M. Klauck, Eftichia Duketis, Fritz Poustka, Sabine Schlitt, Christine M. Freitag, Irene Lee, Pierandrea Muglia, Martin Poot, Wouter Staal, Maretha V. de Jonge, Roel A. Ophoff, Cathryn Lewis, David Skuse, Will Mandy, Evangelos Vassos, Ragnheidur FossdalPáll Magnusson, Stefan Hreidarsson, Evald Saemundsen, Hreinn Stefansson, Kari Stefansson, David Collier

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28 Scopus citations


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.

Original languageEnglish
Pages (from-to)633-639
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number6
StatePublished - Sep 2011
Externally publishedYes


  • Autism
  • Autism spectrum
  • Common genetic risk variants
  • Genetic association


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