Common Genetic Variants in FOXP2 Are Not Associated with Individual Differences in Language Development.

Kathryn L Mueller,J Bruce Tomblin,Sheena Reilly,Jacob J Michaelson,Jeffrey C Murray,Morten H Christiansen,Dana C Crawford

doi:10.1371/journal.pone.0152576

Abstract

Much of our current knowledge regarding the association of FOXP2 with speech and language development comes from singleton and small family studies where a small number of rare variants have been identified. However, neither genome-wide nor gene-specific studies have provided evidence that common polymorphisms in the gene contribute to individual differences in language development in the general population. One explanation for this inconsistency is that previous studies have been limited to relatively small samples of individuals with low language abilities, using low density gene coverage. The current study examined the association between common variants in FOXP2 and a quantitative measure of language ability in a population-based cohort of European decent (n = 812). No significant associations were found for a panel of 13 SNPs that covered the coding region of FOXP2 and extended into the promoter region. Power analyses indicated we should have been able to detect a QTL variance of 0.02 for an associated allele with MAF of 0.2 or greater with 80% power. This suggests that, if a common variant associated with language ability in this gene does exist, it is likely of small effect. Our findings lead us to conclude that while genetic variants in FOXP2 may be significant for rare forms of language impairment, they do not contribute appreciably to individual variation in the normal range as found in the general population.

Highlights

Language acquisition requires the interplay of complex biological and behavioural/learning systems, combined with a stimulating and responsive environment where language serves as a tool for social engagement
By comprehensive SNP genotyping of FOXP2 in a large population-based sample with a continuum of language ability, the current study aimed to address the question of whether common genetic variants in FOXP2 contribute to individual differences in language development
These results were robust even in the face of Random Forests (RF) parameter tuning (RF typically needs little or no parameter tuning for optimal performance). These results suggest that even in a multivariate machine learning paradigm, SNPs in FOXP2 have little or no explanatory power for language phenotypes in our sample. This is the first study to investigate the association of common variants in FOXP2 to individual differences in language ability in a large sample with a range of language abilities

Summary

Introduction

Language acquisition requires the interplay of complex biological and behavioural/learning systems, combined with a stimulating and responsive environment where language serves as a tool for social engagement. While motor speech impairments seem to be universal in these cases, language impairments are common and usually considered a core feature of the phenotype [34] These reports of speech and language impairments in individuals and families with FOXP2 mutations raise the question as to whether common variants in the gene might be associated with individual differences in the general population. Cohort studies of FOXP2 suggest that common variants are unlikely involved in more ‘common’ forms of developmental language impairment identified via clinical and populationbased samples [36, 37] These studies have been limited in number, by relatively small sample sizes, and by low density gene coverage. They have focussed only on individuals with impaired speech and language abilities, with unaffected family members comprising the control group.

Results

Discussion

Materials and Methods