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Genome-Wide Association and Exome Sequencing Study of Language Disorder in an Isolated Population.

Title: Genome-Wide Association and Exome Sequencing Study of Language Disorder in an Isolated Population.
Name(s): Kornilov, Sergey A, author
Rakhlin, Natalia, author
Koposov, Roman, author
Lee, Maria, author
Yrigollen, Carolyn, author
Caglayan, Ahmet Okay, author
Magnuson, James S, author
Mane, Shrikant, author
Chang, Joseph T, author
Grigorenko, Elena L, author
Type of Resource: text
Genre: Journal Article
Date Issued: 2016-04-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Developmental language disorder (DLD) is a highly prevalent neurodevelopmental disorder associated with negative outcomes in different domains; the etiology of DLD is unknown. To investigate the genetic underpinnings of DLD, we performed genome-wide association and whole exome sequencing studies in a geographically isolated population with a substantially elevated prevalence of the disorder (ie, the AZ sample). DNA samples were collected from 359 individuals for the genome-wide association study and from 12 severely affected individuals for whole exome sequencing. Multifaceted phenotypes, representing major domains of expressive language functioning, were derived from collected speech samples. Gene-based analyses revealed a significant association between SETBP1 and complexity of linguistic output (P = 5.47 × 10(-7)). The analysis of exome variants revealed coding sequence variants in 14 genes, most of which play a role in neural development. Targeted enrichment analysis implicated myocyte enhancer factor-2 (MEF2)-regulated genes in DLD in the AZ population. The main findings were successfully replicated in an independent cohort of children at risk for related disorders (n = 372). MEF2-regulated pathways were identified as potential candidate pathways in the etiology of DLD. Several genes (including the candidate SETBP1 and other MEF2-related genes) seem to jointly influence certain, but not all, facets of the DLD phenotype. Even when genetic and environmental diversity is reduced, DLD is best conceptualized as etiologically complex. Future research should establish whether the signals detected in the AZ population can be replicated in other samples and languages and provide further characterization of the identified pathway.
Identifier: FSU_pmch_27016271 (IID), 10.1542/peds.2015-2469 (DOI), PMC4811310 (PMCID), 27016271 (RID), 27016271 (EID), peds.2015-2469 (PII)
Grant Number: P50 HD052120, R01 DC007665, U54 HG006504, UM1 HG006504
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at
Subject(s): Adolescent
Aged, 80 and over
Child, Preschool
Genome-Wide Association Study/methods
Language Disorders/diagnosis
Language Disorders/epidemiology
Language Disorders/genetics
Middle Aged
Polymorphism, Single Nucleotide/genetics
Sequence Analysis, DNA/methods
Young Adult
Persistent Link to This Record:
Host Institution: FSU
Is Part Of: Pediatrics.
Issue: iss. 4, vol. 137

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Kornilov, S. A., Rakhlin, N., Koposov, R., Lee, M., Yrigollen, C., Caglayan, A. O., … Grigorenko, E. L. (2016). Genome-Wide Association and Exome Sequencing Study of Language Disorder in an Isolated Population. Pediatrics. Retrieved from