title: 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.
authors.affiliation: Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Kings College London, UK. sarah.curran@kcl.ac.uk
authors.forename: Sarah
authors.initials: S
authors.lastname: Curran
authors.forename: Patrick
authors.initials: P
authors.lastname: Bolton
authors.forename: Kinga
authors.initials: K
authors.lastname: Rozsnyai
authors.forename: Andreas
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Klauck
authors.forename: Eftichia
authors.initials: E
authors.lastname: Duketis
authors.forename: Fritz
authors.initials: F
authors.lastname: Poustka
authors.forename: Sabine
authors.initials: S
authors.lastname: Schlitt
authors.forename: Christine M
authors.initials: CM
authors.lastname: Freitag
authors.forename: Irene
authors.initials: I
authors.lastname: Lee
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
authors.forename: Martin
authors.initials: M
authors.lastname: Poot
authors.forename: Wouter
authors.initials: W
authors.lastname: Staal
authors.forename: Maretha V
authors.initials: MV
authors.lastname: de Jonge
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.forename: Cathryn
authors.initials: C
authors.lastname: Lewis
authors.forename: David
authors.initials: D
authors.lastname: Skuse
authors.forename: Will
authors.initials: W
authors.lastname: Mandy
authors.forename: Evangelos
authors.initials: E
authors.lastname: Vassos
authors.forename: Ragnheidur
authors.initials: R
authors.lastname: Fossdal
authors.forename: Páll
authors.initials: P
authors.lastname: Magnusson
authors.forename: Stefan
authors.initials: S
authors.lastname: Hreidarsson
authors.forename: Evald
authors.initials: E
authors.lastname: Saemundsen
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: David
authors.initials: D
authors.lastname: Collier
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005060:Europe; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide