Symptom domains in autism and related conditions: Evidence for familiality

Abstract

Heterogeneity in autism impairs efforts to localize and identify the genes underlying this disorder. As autism comprises severe but variable deficits and traits in three symptom domains (social interaction, communication, and repetitive behaviors) and shows variability in the presence and emergence of useful phrase speech, different genetic factors may be associated with each. The affected cases (n=457) in multiply affected siblingships (n=212), including a proband with autism and one or more siblings with either autism or marked deficits in autism symptom domains, were assessed using the Autism Diagnostic Interview, Revised. Symptom domain scores and language features were examined to determine their similarity within siblingships. The variance within siblingships was reduced for the repetitive behavior domain and for delays in and the presence of useful phrase speech. These features and the nonverbal communication subdomain provided evidence of familiality when we considered only the diagnosis of autism to define multiply affected siblingships (cases: n=289; siblingships: n=136). In addition, the same familial features identified also appeared familial for those with autism-related conditions. Finally, the level of severity of almost all of the familial features varied within multiplex siblingships independently. The features identified as familial replicate the combined set suggested in earlier, smaller studies. Furthermore, the familiality of these features extend to related conditions of milder severity than autism and appear to be independent. Making distinctions among families by the severity of these features may be useful for identifying more genetically homogeneous subgroups in studies targeted at genes for specific autism-related symptom domains.

Quantitative genome scan and Ordered-Subsets Analysis of autism endophenotypes support language QTLs

“…23 As shown in Table 1, the modest but significant WORD (r ¼ 0.27), PHRASE (r ¼ 0.30) and RSB (r ¼ 0.31) sibling correlations suggested that the variability in these traits was familial and may have been due to genetic influences; however, the effects of a common sibling environment may have also contributed to these relationships. 37 …”

The genetics of autistic disorders and its clinical relevance: a review of the literature

“…99 Language abilities, however, were not impaired in siblings of children with autism 100 arguing against language abilities as a marker for the BAP. Two other studies, however, did find a reduced variance within autistic sib-ships regarding the onset of phrase speech, 101 and an influence of language abilities on the correlation of ICD-10 autism symptoms and the presence of the BAP in relatives, 102 arguing for a role of language abilities in the genetics of AD. A high concordance for rituals and repetitive play, for social impairments and non-verbal communication in autistic sib-pairs was found in three further studies.…”

“…A high concordance for rituals and repetitive play, for social impairments and non-verbal communication in autistic sib-pairs was found in three further studies. 101,103,104 These studies were interpreted in the same way as the twin studies suggesting the same genetic liability for social and communicative behaviour and a different genetic liability for stereotyped and repetitive behaviour and language development. 105 Assessment of the BAP in parents of children with autism has given similar results.…”

Family‐based association testing of OCD‐associated SNPs of SLC1A1 in an autism sample

“…Relatives of individuals with autism are more likely than relatives of individuals with other developmental disorders to have OCD [Bolton, Pickles, Murphy, & Rutter, 1998;Micali, Chakrabarti, & Fombonne, 2004]. Among affected sibling pairs, two sub-domains of the Autism Diagnostic Interview-Revised [ADI-R, Lord, Rutter, & Le Couteur, 1994], which relate to OCD (''encompassing preoccupations/circumscribed interests'' and ''apparently compulsive adherence to nonfunctional compulsions/ rituals''), show strong familiality [Silverman et al, 2002]. Further, genetic studies have shown greater evidence for linkage in families with autism with higher insistence on sameness scores on chromosome 15q11-q13 (GABRB3) [Shao et al, 2003], greater obsessive-compulsive behaviors on chromosome 1 at the marker D1S1656 [Buxbaum et al, 2004], and increased rigid-compulsive behavior at chromosome 17q11.2 [Sutcliffe et al, 2005].…”