TY - JOUR
T1 - Association between genes regulating neural pathways for quantitative traits of speech and language disorders
AU - Benchek, Penelope
AU - Igo, Robert P.
AU - Voss-Hoynes, Heather
AU - Wren, Yvonne
AU - Miller, Gabrielle
AU - Truitt, Barbara
AU - Zhang, Wen
AU - Osterman, Michael
AU - Freebairn, Lisa
AU - Tag, Jessica
AU - Taylor, H. Gerry
AU - Chan, E. Ricky
AU - Roussos, Panos
AU - Lewis, Barbara
AU - Stein, Catherine M.
AU - Iyengar, Sudha K.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/7/27
Y1 - 2021/7/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85112036316&partnerID=8YFLogxK
U2 - 10.1038/s41525-021-00225-5
DO - 10.1038/s41525-021-00225-5
M3 - Article
AN - SCOPUS:85112036316
SN - 2056-7944
VL - 6
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 64
ER -