Genetic Associations of Speech Sound Disorders and Reading Disorders
Barbara A. Lewis1, Lisa A. Freebairn1, 1Amy J. Hansen, 3Lawrence D. Shriberg, 2Catherine M. Stein, 2Sudha Iyengar, 1H. Gerry Taylor 1Department of Pediatrics, 2Department of Epidemiology and Biostatistics Case Western Reserve University, School of Medicine Cleveland, Ohio 3 Waisman Center, University of Wisconsin, Madison
Supported by National Institutes of Health, National Institute on Deafness and Other Communication Disorders, Grant DC00528 NIDCD grant
Abstract
Families were recruited through a preschool child who was enrolled in speech/language therapy for a moderate to severe SSD. Behavioral testing was used to phenotype 149 families (~417 sib pairs) with an extensive battery of cognitive-linguistic measures including assessments of articulation, oral motor skills, phonological processing, vocabulary, reading, and spelling. Model-free linkage analyses of speech-related phenotypes was conducted on candidate chromosome regions previously linked to RD phenotypes on chromosome 3, 6, and 15 using quantitative trait linkage methods, e.g. the Haseman-Elston Method, and conditional logistic methods to analyze binary traits. Chromosome 3 showed linkage for phonological encoding (p=2x105), speech-sound production (p=0.00015), phonological memory (p=0.023) and single word reading (p=0.004). Chromosome 6 findings were similar to those for 3 with phonological encoding showing the strongest linkage (p=7x10-5). Chromosome 15 was linked to the binary trait of SSD (p=0.004) and oral motor skills (p=0.048). These results support the hypothesis that SSD and RD are influenced by the common genetic loci.
Participants
Families for the study were recruited from the caseloads of speech/language pathologists in Northeast Ohio. Proband children were required to have: • Normal hearing, nonverbal IQ, and oral motor skills.
Results of Linkage Analyses
Chromosome 3
4.5 4 3.5
Chromosome 15
Chromosome 15 Speech
3.00
• Deficits of speech sounds in single words as evidenced by a score below the 10th percentile on the Goldman-Fristoe Test of Articulation (GFTA), a minimum occurrence of four phonological process errors and a severity rating of 3-4 (moderate to severe) on the Khan-Lewis Phonological Analysis (KLPA) • Speech-sound errors in conversational speech with a rating of less than 90 percent consonant correct (PCC).
3 2.5
pP
ARTF PHONF VOCF
2.50
2 1.5
2.00
1 0.5
pP
1.50
all ethnicities Caucasians only
0
D3S1766 D3S1285 D3S2454 D3S2406 D3S3049 D3S3681 D3S2465 D3S1595 D3S1752 D3S2462 D3S3716 D3S3655 D3S2459 D3S3045 D3S2460
markers
1.00
Sample Characteristics
Pedigrees Individuals Males/Females Sibling Pairs Concordantly affected 151 664 359/305 358 113
Chromosome 6
0.50
0.00
2.0 cM 4.0 cM 6.0 cM 8.0 cM 10.0 cM 12.0 cM 14.0 cM 16.0 cM 18.0 cM 20.0 cM D15S118 D15S214 D15S143 D15S126 D15S209 22.0 cM D15S117
Introduction
Speech Sound Disorder (SSD) is a complex behavioral disorder characterized by speech-sound production errors associated with deficits in articulation, phonological processing, and cognitive-linguistic skills. The behavioral phenotypes associated with SSD are not static; rather they follow a developmental trajectory. SSD is often co-morbid with language impairment (LI) at preschool age and later with reading disorders (RD) at school-age (Lewis & Freebairn, 2000). SSD and RD rely on common neuropsychological processes, such as phonological awareness and phonological memory (Pennington & Lefly, 2001; Raitano, Pennington, Boada, & Shriberg, 2004; Tunick & Pennington, 2002). These phonological processes may be influenced by genes that place an individual at risk for SSD and RD. Genetic linkage studies of RD have identified candidate chromosome regions and several candidate genes for RD. We hypothesized that SSD and RD disorders may share common genetic influences. The goal of the present study was to assess the genetic overlap of SSD and RD through model-free linkage analysis to candidate chromosome regions that were previously associated with RD on chromosomes 3,6, and 15. We hypothesized that SSD and RD result from common deficits in phonological processing including phonological awareness, memory, and phonological representations.
Conclusions
We detected linkage to a number of RD-susceptibility regions with our study population that was ascertained through a proband with SSD.
Behavioral Measures
•Speech Sound Measures •Goldman-Fristoe Test of Articulation •Conversational Speech Sample •Multisyllabic Word Repetition •Phonological Processing Measures •Segmentation •Elision •Nonword Repetition •Rapid Serial Naming •Phonological Memory- Sentence Imitation •Oral Motor Skills •Vocabulary •Peabody Picture Vocabulary Test •Expressive One Word Picture Vocabulary •Reading •Woodcock Reading Mastery Test •WIAT Reading Comprehension •Spelling •Test of Written Spelling-3
Chromosome Regions Associated with Dyslexia
Chromosome 3 showed linkage for phonological encoding, speech-sound production, phonological memory, and single word reading. Chromosome 6 findings were similar to those for 3 with phonological encoding showing the strongest linkage. Chromosome 15 was linked to the binary trait of SSD and oral motor skills. These results support the hypothesis that SSD and RD are influenced by common genetic loci. While chromosomes 3 and 6 showed similar patterns of linkage, chromosome 15 linked to quantitative traits that were more related to speechsound production than reading. These findings suggest SSD may be influenced by both shared genes with RD and genes that are unique to SSD.