Quantitative genetic studies have consistently demonstrated a heritable component for specific language impairment (SLI). However, only a handful of groups have begun assessing the genetic epidemiology of SLI. In a previous phase of our ongoing research, we found compelling evidence for a risk polymorphism within 13q21-22, which was subsequently replicated. However, the specific susceptibility allele that acts to increase risk for SLI within 13q21 region has not yet been identified. Equally important, previous studies have not examined the genetic etiology or etiologies of SLI in the context of the multiple, quantitatively distributed underlying language processes that may lead to SLI. Thus, the relationship between the substantial clinical heterogeneity among individuals with SLI and concomitant genetic heterogeneity remains largely unexplored. The goal of this application, therefore, is to address three specific aims. We proposed to localize SLI susceptibility alleles by applying a combination of multi-level approaches. We will use bioinformatics and molecular approaches to identify possible susceptibility-allele-harboring sequences within 13q21 (Aim 1). We will extend our family collection to increase power to detect novel SLI loci and SLI-related QTLs (Aim 2). We will employ new multivariate approaches which are expected to better refine our localization, increase power, and allow us to examine these loci in the multivariate context of several underlying language processes from the SLI literature (Aim 3).
These aims are important because they link genetic analysis with the multiple cognitive pathways that may lead to SLI in the hopes of better identification and treatment.

Public Health Relevance

Specific language impairment is a common disorder;approximately 5-7 percent of school age children meet criteria for specific language impairment and collectively these children represent the largest portion of pupils receiving special education services within the nation's public school system. Understanding the variety of genetic risk factors and negatively influences language development may lead to earlier identification and hence earlier treatment, and may also help in the development of new therapeutic approaches based on the underlying neurobiology.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009453-02
Application #
8035976
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Cooper, Judith
Project Start
2010-04-01
Project End
2015-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
2
Fiscal Year
2011
Total Cost
$705,516
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
Bruni, Matthew; Flax, Judy F; Buyske, Steven et al. (2017) Behavioral and Molecular Genetics of Reading-Related AM and FM Detection Thresholds. Behav Genet 47:193-201
Goode, Michael R; Cheong, Soo Yeon; Li, Ning et al. (2014) Collection and extraction of saliva DNA for next generation sequencing. J Vis Exp :
Wolock, Samuel L; Yates, Andrew; Petrill, Stephen A et al. (2013) Gene × smoking interactions on human brain gene expression: finding common mechanisms in adolescents and adults. J Child Psychol Psychiatry 54:1109-19
Hou, Liping; Wang, Kai; Bartlett, Christopher W (2012) Evaluation of a bayesian model integration-based method for censored data. Hum Hered 74:1-11
Li, Ning; Bartlett, Christopher W (2012) Defining the genetic architecture of human developmental language impairment. Life Sci 90:469-75
Logan, Jessica; Petrill, Stephen A; Flax, Judy et al. (2011) Genetic covariation underlying reading, language and related measures in a sample selected for specific language impairment. Behav Genet 41:651-9
Hou, Liping; Phillips, Christopher; Azaro, Marco et al. (2011) Validation of a cost-efficient multi-purpose SNP panel for disease based research. PLoS One 6:e19699
Simmons, Tabatha R; Flax, Judy F; Azaro, Marco A et al. (2010) Increasing genotype-phenotype model determinism: application to bivariate reading/language traits and epistatic interactions in language-impaired families. Hum Hered 70:232-44