Common variant of CNTNAP2 gene modulate the social performances and functional connectivity of posterior right temporoparietal junction

Abstract

Social deficits are features of autism and highly heritable traits. A common variant in autism-related CNTNAP2 gene, rs2710102, has been linked with social performance, but the neural substrates are largely unknown. We investigated variations in social performance and functional connectivity (static and dynamic) in the subregions of right temporoparietal junction (RTPJ), a key node of brain social network, using resting-state magnetic resonance imaging (n = 399) by genotype at rs2710102 in healthy volunteers. Social performance was evaluated using the social domain of the Autism-Spectrum Quotient (AQ-social; n = 641) and fixation time on eye areas during an eye-tracking task (n = 32). According to previous evidence that the A-allele is the risk allele for social dysfunction, we classified participants into GG and A-allele carriers (AA/AG) groups. The A-allele carriers showed poor social performance (high AQ-social and short fixation time on eye areas) compared with the GG carriers. In the A-allele carriers, decreased stationary functional connectivity between the orbitofrontal cortex and posterior RTPJ (pRTPJ), and decreased dynamic functional connectivity (dFC) between the medial prefrontal cortex (mPFC) and pRTPJ were observed. The fixation time at eye areas positively were correlated with the pRTPJ-mPFC dFC. These findings provided insight for genetic effect on social behavior and its potential neural substrate.

A common variant of CNTNAP2 is associated with sub-threshold autistic traits and intellectual disability

“…According to the selected genetic model [ 48 ], we transformed the three genotypes (AA, AG, and GG) into two variables. In particular, considering our results and the findings of previous studies [ 21 ], we assumed the co-dominant model: Carriers of the A-allele (AA + AG) versus G-allele homozygotes. This indicates that allele A increases autistic traits.…”

“…Among single nucleotide polymorphisms (SNPs) of CNTNAP2 , rs2710102 (G/A, intron13) is one of the most frequently reported to be associated with autistic traits [ 17 ]. G-allele of rs2710102 has been associated with language impairments in individuals with and without ASD [ 18 – 20 ], but more importantly, having an A-allele of this SNP is associated with autistic traits in the general population [ 21 – 23 ], for example, having high AQ-social scores [ 21 ] and high social anxiety-related traits [ 22 ] in young adults (i.e., college students). Steer et al .…”

The Cingulate Structures in Autism Spectrum Disorder: Exploring Its Implication on Social Awareness and the Role of CNTNAP2

“…Genomic DNA was prepared from peripheral blood using the Puregene DNA puri cation system (Gentra Systems Inc. Minneapolis, MI) according to the manufacturer's instructions. Five SNPs of the CNTNAP2, located in the intron 2 (rs779475) [37,39], intron 13 (rs759178, rs2710102, rs2538991) [28,40,41], and intron 15 (rs2710126) [40], were selected for genotyping based on previous imaging genetic studies.…”

“…The CNTNAP2, an autism susceptibility gene [23,24,[33][34][35][36], was reported to be associated with GM and WM volume [37][38][39] and structural disconnectivity [27,28,40] in several regions that had already been implicated in ASD, including the cerebellum [39], fusiform gyrus, occipital [37] and frontal cortices [28,38]. Several common variants of the CNTNAP2 were reported to be associated with reduced GM volumes (e.g., rs7794745) [37,39], structural connectivity (e.g., rs2710102 [28], rs2710126, rs759178, and rs2538991 [40]), and functional connectivity (of posterior right temporoparietal junction with rs2710102 [41]). These variants overlap with the SNPs that are associated with the risks for ASD [23,35], early communicative di culty [33,[42][43][44], or social performance [41], particularly the SNPs in intron 13.…”

“…Several common variants of the CNTNAP2 were reported to be associated with reduced GM volumes (e.g., rs7794745) [37,39], structural connectivity (e.g., rs2710102 [28], rs2710126, rs759178, and rs2538991 [40]), and functional connectivity (of posterior right temporoparietal junction with rs2710102 [41]). These variants overlap with the SNPs that are associated with the risks for ASD [23,35], early communicative di culty [33,[42][43][44], or social performance [41], particularly the SNPs in intron 13. The genetic effects of these ve SNPs of the CNTNAP2 gene would be tested herein for its role in the cingulate structure.…”