A rare WNT1 missense variant overrepresented in ASD leads to increased Wnt signal pathway activation.

TitleA rare WNT1 missense variant overrepresented in ASD leads to increased Wnt signal pathway activation.
Publication TypeJournal Article
Year of Publication2013
AuthorsMartin P-M, Yang X, Robin N, Lam E, Rabinowitz JS, Erdman CA, Quinn J, Weiss LA, Hamilton SP, Kwok P-Y, Moon RT, Cheyette BNR
JournalTranslational psychiatry
Volume3
Paginatione301
Date Published9
ISSN2158-3188
Abstract{Wnt signaling, which encompasses multiple biochemical pathways that regulate neural development downstream of extracellular Wnt glycoprotein ligands, has been suggested to contribute to major psychiatric disorders including autism spectrum disorders (ASD). We used next-generation sequencing and Sequenom genotyping technologies to resequence 10 Wnt signaling pathway genes in 198 ASD patients and 240 matched controls. Results for single-nucleotide polymorphisms (SNPs) of interest were confirmed in a second set of 91 ASD and 144 control samples. We found a significantly increased burden of extremely rare missense variants predicted to be deleterious by PolyPhen-2, distributed across seven genes in the ASD sample (3.5% in ASD vs 0.8% in controls; Fisher's exact test, odds ratio (OR)=4.37
DOI10.1038/tp.2013.75