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

Yuka Shiota; Tetsu Hirosawa; Yuko Yoshimura; Sanae Tanaka; Chiaki Hasegawa; Sumie Iwasaki; Kyung-Min An; Daiki Soma; Masuhiko Sano; Shigeru Yokoyama; Mitsuru Kikuchi

doi:10.1371/journal.pone.0260548

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

PLoS One. 2021 Dec 13;16(12):e0260548. doi: 10.1371/journal.pone.0260548. eCollection 2021.

Authors

Yuka Shiota^{1

2}, Tetsu Hirosawa^{1

2

3}, Yuko Yoshimura^{1

4}, Sanae Tanaka^{1

2}, Chiaki Hasegawa², Sumie Iwasaki², Kyung-Min An^{1

2}, Daiki Soma³, Masuhiko Sano³, Shigeru Yokoyama^{1

2}, Mitsuru Kikuchi^{1

2

3}

Affiliations

¹ United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Kanazawa, Japan.
² Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan.
³ Department of Psychiatry and Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
⁴ Institute of Human and Social Sciences, Kanazawa University, Kanazawa, Japan.

Abstract

Sub-threshold autistic traits are common in the general population. Children with sub-threshold autistic traits have difficulties with social adaptation. Contactin-associated protein-like 2 (CNTNAP2) is associated with the development of Autism spectrum disorder (ASD) and the single-nucleotide polymorphism rs2710102 (G/A) of CNTNAP2 is suggested to contribute to sub-threshold social impairments and intellectual disabilities. We recruited 67 children with Autistic disorder (AD) (49 boys, 18 girls, aged 38-98 months) and 57 typically developing (TD) children (34 boys, 23 girls, aged 53-90 months). We assessed the participants' intelligence and social reciprocity using the Kaufman Assessment Battery for Children (K-ABC) and the Social Responsiveness Scale (SRS), respectively. Genomic DNA was extracted from the buccal mucosa and genotyped for rs2710102. A chi-square test revealed a significant association between genotype and group [χ2(2) = 6.56, p = 0.038]. When a co-dominant model was assumed, the results from linear regression models demonstrated that TD children with A-carriers (AA + AG) presented higher SRS T-scores [t(55) = 2.11, p = 0.039] and lower simultaneous processing scale scores of K-ABC [t(55) = -2.19, p = 0.032] than those with GG homozygotes. These associations were not significant in children with ASD. TD children with the rs2710102 A-allele may have more sub-threshold autistic traits than those with GG homozygotes, reflected in higher SRS scores and lower simultaneous processing scale scores. These results support the use of genetic evidence to detect sub-threshold autistic traits.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Autistic Disorder / diagnosis*
Autistic Disorder / genetics
Child
Child, Preschool
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Homozygote
Humans
Intellectual Disability / diagnosis*
Intellectual Disability / genetics
Intelligence Tests
Japan
Male
Membrane Proteins / genetics*
Nerve Tissue Proteins / genetics*
Polymorphism, Single Nucleotide

Substances

CNTNAP2 protein, human
Membrane Proteins
Nerve Tissue Proteins

Grants and funding

This work was supported by JSPS KAKENHI grants (Grant Number 20H03599) to MK, [Grant Numbers 20K16623] to TH, and the Center of Innovation Program of the Japan Science and Technology Agency, JST, Japan [supported by a grant from the Collaborative Research Program of the Collaborative Research Network for Asian Children with Developmental Disorders]. NO - Include this sentence at the end of your statement: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.