A Common Genetic Variant in the Neurexin Superfamily Member CNTNAP2 Is Associated with Increased Risk for Selective Mutism and Social Anxiety-Related Traits

作者：Stein Murray B^*; Yang Bao Zhu; Chavira Denise A; Hitchcock Carla A; Sung Sharon C; Shipon Blum Elisa; Gelernter Joel

来源：Biological Psychiatry, 2011, 69(9): 825-831.

DOI：10.1016/j.biopsych.2010.11.008

• Anxiety disorders
• autism
• autism spectrum
• behavioral inhibition
• childhood
• genetics
• social anxiety
• speech

Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.

• 出版日期2011-5-1