A Genomewide Scan Identifies Two Novel Loci Involved in Specific Language Impairment**Members of the consortium are listed in the Appendix.

Abstract

Approximately 4% of English-speaking children are affected by specific language impairment (SLI), a disorder in the development of language skills despite adequate opportunity and normal intelligence. Several studies have indicated the importance of genetic factors in SLI; a positive family history confers an increased risk of development, and concordance in monozygotic twins consistently exceeds that in dizygotic twins. However, like many behavioral traits, SLI is assumed to be genetically complex, with several loci contributing to the overall risk. We have compiled 98 families drawn from epidemiological and clinical populations, all with probands whose standard language scores fall > or =1.5 SD below the mean for their age. Systematic genomewide quantitative-trait-locus analysis of three language-related measures (i.e., the Clinical Evaluation of Language Fundamentals-Revised [CELF-R] receptive and expressive scales and the nonword repetition [NWR] test) yielded two regions, one on chromosome 16 and one on 19, that both had maximum LOD scores of 3.55. Simulations suggest that, of these two multipoint results, the NWR linkage to chromosome 16q is the most significant, with empirical P values reaching 10(-5), under both Haseman-Elston (HE) analysis (LOD score 3.55; P=.00003) and variance-components (VC) analysis (LOD score 2.57; P=.00008). Single-point analyses provided further support for involvement of this locus, with three markers, under the peak of linkage, yielding LOD scores >1.9. The 19q locus was linked to the CELF-R expressive-language score and exceeds the threshold for suggestive linkage under all types of analysis performed-multipoint HE analysis (LOD score 3.55; empirical P=.00004) and VC (LOD score 2.84; empirical P=.00027) and single-point HE analysis (LOD score 2.49) and VC (LOD score 2.22). Furthermore, both the clinical and epidemiological samples showed independent evidence of linkage on both chromosome 16q and chromosome 19q, indicating that these may represent universally important loci in SLI and, thus, general risk factors for language impairment.

The impact of phonological complexity on past tense inflection in children with Grammatical-SLI

“…It is becoming clear that there is no single genetic 'cause' of SLI, and that genetic investigations require theoretically motivated measures of underlying cognitive abilities (Bishop, 2006). One locus on Chromosome 16 has been linked to performance on non-word repetition task, which is a phonological task, whereas a locus on Chromosome 19 has been linked to expressive language tasks that require syntax (SLI Consortium, 2002). Similarly, a behavioural genetics study by Bishop, Adams and Norbury (2006) implicated different genes appear in phonological short-term memory and verb inflection deficits in SLI.…”

Language in autism and specific language impairment: Where are the links?

“…The most reliable linkage signals in SLI have come from sites on chromosomes 16q (SLI consortium, 2002(SLI consortium, , 2004) and 19q (Bartlett et al, 2003;SLI consortium, 2002SLI consortium, , 2004. Neither of these has been reliably indicated in studies of autism.…”

Family-based association study of DYX1C1 variants in autism

“…14 -16 Noteworthy, also most samples with specific language impairment (SLI) have failed to show any linkage or association signals at the FOXP2 locus, indicating that it is unlikely to play a significant role in cases of typical SLI. 14,17,18 However, one recent study showed putative evidence for association of FOXP2 locus with SLI. 19 In a Finnish dyslexia sample, linkage for 7q31 overlapping SPCH1 and AUTS1 loci was observed, but sequencing of FOXP2 in dyslexic individuals revealed no coding sequence mutations.…”