
Letter to the Editor
Molecular Psychiatry advance online publication 22 October 2013; doi: 10.1038/mp.2013.125
Response to ‘Predicting the diagnosis of autism spectrum disorder using gene pathway analysis’
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E B Robinson1,2,3, D Howrigan1,2,3, J Yang4,5, S Ripke1,2,3,6, V Anttila1,2,3,6, L E Duncan3,7,8,9, L Jostins10, J C Barrett10, S E Medland11, D G MacArthur1,2,3, G Breen12, M C O'Donovan13, N R Wray4,5, B Devlin14, M J Daly1,2,3,6, P M Visscher4,5, P F Sullivan15 and B M Neale1,2,3,6
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Department of Medicine, Harvard Medical School, Boston, MA, USA
3Medical and Population Genetics Program, Broad Institute for Harvard and MIT, Cambridge, MA, USA
4The University of Queensland, Queensland Brain Institute, Brisbane, QLD, Australia
5The Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia
6Stanley Center for Psychiatric Research, Broad Institute for Harvard and MIT, Cambridge, MA, USA
7Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
8Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts, General Hospital, Boston, MA, USA
9Department of Psychiatry, Harvard Medical School, Boston, MA, USA
10Wellcome Trust Sanger Institute, Cambridge, UK
11Queensland Institute of Medical Research, Brisbane, QLD, Australia
12Social Genetic and Developmental Psychiatry Center, Institute of Psychiatry, King’s College London, London, UK
13MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University School of Medicine, Cardiff, UK
14Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
15Department of Genetics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
Correspondence: BM Neale, E-mail:
[email protected]In a recent paper published online in Molecular Psychiatry, Skafidas et al.1 report a classifier for identifying individuals at risk for autism spectrum disorders (ASDs). Their classifier is based on 267 single-nucleotide polymorphisms (SNPs) that were selected from the results of a pathway analysis using cases from the Autism Genetic Resource Exchange (AGRE).1 Using within-sample cross-validation, the authors claim a classification accuracy for ASDs of 85.6%. They subsequently applied their classifier to ASD cases from the Simons Foundation Autism Research Initiative (SFARI) and controls from the Wellcome Trust Birth Cohort (WTBC) and report ASD classification accuracy of 71.7%.
We believe that the claims made by Skafidas et al.1 are inconsistent with current knowledge of the genetics of ASDs,2 and inconsistent with the expected precision of risk predictions for complex psychiatric disorders. Further, as classification accuracy depends on the size of the discovery sample, the results are also inconsistent with the size of the sample they employed (only 123 controls were included in the discovery set).