Association between genes regulating neural pathways for quantitative traits of speech and language disorders

Penelope Benchek,Barbara Lewis,Jessica Tag,Panos Roussos,Lisa Freebairn,Barbara Truitt,Yvonne Wren,Michael Osterman,H Gerry Taylor,E Ricky Chan,Wen Zhang,Sudha K Iyengar,Catherine M Stein,Robert P Igo,Heather Voss-Hoynes,Gabrielle Miller

doi:10.1038/s41525-021-00225-5

Abstract

Speech sound disorders (SSD) manifest as difficulties in phonological memory and awareness, oral motor function, language, vocabulary, reading, and spelling. Families enriched for SSD are rare, and typically display a cluster of deficits. We conducted a genome-wide association study (GWAS) in 435 children from 148 families in the Cleveland Family Speech and Reading study (CFSRS), examining 16 variables representing 6 domains. Replication was conducted using the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 18 significant loci (combined p < 10−8) that we pursued bioinformatically. We prioritized 5 novel gene regions with likely functional repercussions on neural pathways, including those which colocalized with differentially methylated regions in our sample. Polygenic risk scores for receptive language, expressive vocabulary, phonological awareness, phonological memory, spelling, and reading decoding associated with increasing clinical severity. In summary, neural-genetic influence on SSD is primarily multigenic and acts on genomic regulatory elements, similar to other neurodevelopmental disorders.

Highlights

Communication disorders are highly prevalent in the UnitedStates with approximately one in twelve children ages 3–17 years demonstrating a disorder[1]
Circles shown are for results significant at p < 0.05, with increasing diameter/color corresponding with increasing correlation
genome-wide association study (GWAS) to include a measure of phonological awareness, as well as a motor speech measure

Summary

Introduction

Communication disorders are highly prevalent in the United. States with approximately one in twelve children ages 3–17 years demonstrating a disorder[1]. The most common difficulties are a speech problem (5%) or language problem (3.3%). Speech sound disorders (SSD) refer to difficulties producing certain sound past the age that a child is expected to acquire the sound, and include both errors of articulation or phonetic structure (errors due to poor motor abilities associated with the production of speech sounds) and phonological errors (errors in applying linguistic rules to combine sounds to form words). SSD has a prevalence of approximately 16% in children 3 years of age[2], with an estimated. Because of the clinical heterogeneity of speech problems and their correlation with other communication domains, endophenotypes are key to the study of genetic underpinnings[9]

Methods

Results

Conclusion