Further evidence of pleiotropy influencing speech and language: analysis of the DYX8 region.
OBJECTIVE
Genetic studies have raised the possibility of common bases for cognitive linguistic disorders such as speech sound disorder (SSD), reading disorder (RD) and language impairment (LI). Thus, some of the same genes may jointly influence cognitive components within and between these three disorders. We examined the plausibility of this theory in a sample of families ascertained on the basis of a child with SSD.


METHODS
Using the method of generalized estimating equations to solve a bivariate family predictive model we obtained measures of comorbidity and familial aggregation of SSD and LI. We then used two methods of multipoint model-free linkage analysis to evaluate SSD and LI psychometric test measures over a region previously implicated in linkage studies of RD, DYX8 region, 1p34-p36.


RESULTS
Bivariate phenotypic analyses show evidence of comorbidity and within family aggregation and coaggregation of SSD and LI. In addition, two regions on chromosome 1 show suggestive evidence of linkage. The first region was previously reported in dyslexia studies. Our maximum linkage signal in this region measured articulation (p = 0.0009) in SSD sibling pairs. The second region is characterized by processes involved in language production, with the maximum linkage signal measuring listening comprehension (p = 0.0019) using all sibling pairs.


CONCLUSIONS
We conclude that the DYX8 region could bear genes controlling pleiotropic effects on SSD, LI and RD.
Miscimarra
L
L
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Stein
C
C
Millard
C
C
Kluge
A
A
Cartier
K
K
Freebairn
L
L
Hansen
A
A
Shriberg
L
L
Taylor
H G
HG
Lewis
B
B
Iyengar
S K
SK
D001184:Articulation Disorders / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004410:Dyslexia / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007805:Language Development Disorders / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D016017:Odds Ratio; D010375:Pedigree