A Genome Scan for Loci Shared by Autism Spectrum Disorder and Language Impairment

Abstract

Objective The authors conducted the first genetic linkage study of families that segregate both autism and specific language impairment to find common communication impairment loci. The hypothesis was that these families have a high genetic loading for impairments in language ability, thus influencing the language and communication deficits of the family members with autism. Comprehensive behavioral phenotyping of the families also enabled linkage analysis of quantitative measures, including normal, subclinical and disordered variation in all family members for the three general autism symptom domains: social, communication, and compulsive behaviors. Method The primary linkage analysis coded persons with either autism or specific language impairment as “affected” with language impairment. The secondary linkage analysis consisted of quantitative metrics of autism-associated behaviors capturing normal to clinically severe variation, measured in all family members. Results Linkage to language phenotypes was established at two novel chromosomal loci, 15q23-26 and 16p12. The secondary analysis of normal and disordered quantitative variation in social and compulsive behaviors established linkage to two loci for social behaviors (at 14q and 15q) and one locus for repetitive behaviors (at 13q). Conclusion These data indicate shared etiology of autism and specific language impairment at two novel loci. Additionally, non-language phenotypes based on social aloofness and rigid personality traits showed compelling evidence for linkage in this sample. Further genetic mapping is warranted at these loci.

Molecular Genetic Evidence for Shared Etiology of Autism and Prodigy

“…Here, the point-wise p value was estimated by performing 11,000 phenotype permutations and determining how many null replicates exceeded the observed PPL in the main linkage analysis. These data are consistent with the genome-wide cut-off from other studies [29][30][31] requiring a PPL of at least 27% and a posterior probability of association (PPLD) to be at least 9% for nominal association of p < 0.001.…”

Discourse/Conversation Analysis and Autism Spectrum Disorder

“…For example, some work attempts to categorise or quantify types of language and communication profiles and/or phenomena that may be presented by people diagnosed with ASD (e.g., Kwok et al 2015). A greater body of work uses experimental paradigms to attempt to identify language-oriented cognitive, neurophysiological or genetic differences in people diagnosed with ASD, and then examine potential associations between these and language performance by such individuals (e.g., Boucher et al 2008;Bartlett et al 2014).…”

Social Responsiveness, an Autism Endophenotype: Genomewide Significant Linkage to Two Regions on Chromosome 8

“…Coon et al (2010) performed linkage analyses for SRS in 64 multiplex families and identified significant non-parametric linkage to chr15q13.3 (LOD 3.64) and suggestive linkage to chr7q31.1-q32.3 (LOD 2.91) (15). In a collection of 70 families segregating ASD with or without language impairment, Bartlett et al (2014) reported strong linkage to SRS as a quantitative trait at chr15q26.2-26.3 and as a dichotomous trait at chr14q32.2-32.33 (34). These studies observed little or no evidence for linkage on chromosome 8p21.3 or 8q24.22; we observe a similar lack of signal in their regions of interest.…”