A Behavioral Genetics Study of Autism, NJLAGS

Background: The New Jersey Language and Autism Genetics Study (NJLAGS) is an ongoing innovative study that combines comprehensive genetic analyses with an extensive evaluation of the oral language, reading, social, and behavioral profiles of families who have at least one member who meets criteria for an autism spectrum disorder (ASD) and at least one other family member who meets criteria for a specific language impairment (SLI). There are research groups who have examined the language patterns of individuals with ASD in relation to the language profiles of individuals with SLI and found striking similarities (Condouris, Smith, Arin, & Tager-Flusberg, 2001, 2004; Conti Ramsden, Simkin, & Botting, 2006; Whitehouse, 2008). NJLAGS extends this line of research to first and second degree relatives of ascertained ASD and SLI probands and combines it with the current work of geneticists who are examining linkage and candidate genes for both disorders (Alarcon, et al., 2004, 2008; Bartlett, et al., 2002, 2004; Brune, et al., 2007; Bradford, et al., 2001).

Objectives: As in introduction to the study, we will present NJLAGS in terms of its criteria for eligibility, the behavioral testing battery administered to subjects, the language phenotypes already developed, and preliminary language profiles of our ASD and SLI subjects to date.

Methods: Potential ASD probands are diagnosed using the ADI-R, the ADOS, and a comprehensive physician’s examination including the DSM-IV. SLI probands are diagnosed by a licensed Speech/Language Pathologist. Once it is determined that there are two probands, the rest of the nuclear family complete a comprehensive neuropsychological battery and donate a blood sample for DNA analysis.

Results: Thus far, 381 family members have given DNA samples and have completed the entire comprehensive behavioral battery. We have identified 80 subjects who meet criteria for Autism and 16 subjects who meet criteria for ASD. Included here is a preliminary profile of their language. Based on the ADI-R, 38% produced single word utterances by 24 months while 62% either produced them later than 24 months or are still non-verbal. Twenty eight percent of our sample has achieved phrase speech by 36 months while 72% achieved this later or still have not achieved this milestone. We examined the group of higher functioning ASD probands who were able to participate in the standardized language testing that was administered to other family members. As a group, the ASD probands scored between one and two standard deviations below matched peers on all language measures with relative strengths in various forms of vocabulary knowledge and relative weaknesses in grammar, inferential language, and the pragmatic use of language. Approximately 29% of family members met criteria for SLI based on at least four different phenotypes.

Conclusions: This research is the first large genetics study to look at the connection between language-based learning problems and autism in New Jersey. Detailed descriptions of the phenotypes and affectation rates of family members will be included as well as how these phenotypes might be applied to linkage analysis and already identified candidate genes.