%0 Journal Article
%T An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males
%A Ren-Hua Chung
%A Deqiong Ma
%A Kai Wang
%A Dale J Hedges
%A James M Jaworski
%A John R Gilbert
%A Michael L Cuccaro
%A Harry H Wright
%A Ruth K Abramson
%A Ioanna Konidari
%A Patrice L Whitehead
%A Gerard D Schellenberg
%A Hakon Hakonarson
%A Jonathan L Haines
%A Margaret A Pericak-Vance
%A Eden R Martin
%J Molecular Autism
%D 2011
%I BioMed Central
%R 10.1186/2040-2392-2-18
%X We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set.One SNP, rs17321050, in the transducin ¦Â-like 1X-linked (TBL1X) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (P value = 4.86 ¡Á 10-6) and joint analysis (P value = 4.53 ¡Á 10-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (P = 5.89 ¡Á 10-3) and passed the replication threshold in the validation data set (P = 2.56 ¡Á 10-4). Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis.TBL1X is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing TBL1X and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that TBL1X may play a role in ASD risk.Autism spectrum disorder (ASD) is a complex disorder of neurodevelopmental origin which is characterized by a well-established set of social, communicative and behavioral impairments [1]. These impairments confer a significant burden on individuals with ASD and their families. This burden, in conjunction with a high ASD prevalence (about 1 in 100 children ages 3 to 17 years in the United States) [2], has spurred aggressive efforts to identify ASD risk genes. Often reported but poorly understood clinical phenomena with implications for gene discovery efforts in AS
%U http://www.molecularautism.com/content/2/1/18