Analysis of expression Quantitative Trait Loci for NLGN4X in relation to language and neurodevelopmental function: an exploratory analysis using FUSION and GTEx workflows

Language disorders in children are highly heritable, but progress in identifying genetic variants that contribute to language phenotypes has been slow. Here we applied a novel approach by identifying SNPs that are associated with gene expression in the brain, taking as our focus a gene on the X chromosome, NLGN4X, which has been postulated to play a role in neurodevelopmental disorders affecting language and communication. We found no significant associations between expression quantitative trait loci (eQTLs) and phenotypes of nonword repetition, general language ability or neurodevelopmental disorder in two samples of twin children, who had been selected for a relatively high rate of language problems. We report here our experiences with two methods, FUSION and GTEx, for eQTL analysis. It is likely that our null result represents a true negative, but for the interest of others interested in using these methods, we note specific challenges encountered in applying this approach to our data: a) complications associated with studying a gene on the X chromosome; b) lack of agreement between expression estimates from FUSION and GTEx; c) software compatibility issues with different versions of the R programming language.