A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-related traits.

ABSTRACT: Selective mutism (SM), considered an early-onset variant of social anxiety disorder, shares features of impaired social interaction and communication with autism spectrum disorders (ASDs) suggesting a possible shared pathophysiology. We examined association of a susceptibility gene, contactin-associated protein-like 2 (CNTNAP2), for ASDs and specific language impairment with SM and social anxiety-related traits.Sample 1 subjects were 99 nuclear families including 106 children with SM. Sample 2 subjects were young adults who completed measures of social interactional anxiety (n = 1028) and childhood behavioral inhibition (n = 920). Five single nucleotide polymorphisms in CNTNAP2 (including rs7794745 and rs2710102, previously associated with ASDs) were genotyped.Analyses revealed nominal significance (p = .018) for association of SM with rs2710102, which, with rs6944808, was part of a common haplotype associated with SM (permutation p = .022). Adjusting for sex and ancestral proportion, each copy of the rs2710102*a risk allele in the young adults was associated with increased odds of being >1 SD above the mean on the Social Interactional Anxiety Scale (odds ratio = 1.33, p = .015) and Retrospective Self-Report of Inhibition (odds ratio = 1.40, p = .010).Although association was found with rs2710102, the risk allele (a) for the traits studied here is the nonrisk allele for ASD and specific language impairment. These findings suggest a partially shared etiology between ASDs and SM and raise questions about which aspects of these syndromes are potentially influenced by CNTNAP2 and mechanism(s) by which these influences may be conveyed.

SUBMITTER: Stein MB 

PROVIDER: S-EPMC3079072 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature