Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230022, China; Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, 230022, China; School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230022, China.
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230022, China; Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, 230022, China.
Behav Brain Res. 2021 Jul 9;409:113319. doi: 10.1016/j.bbr.2021.113319. Epub 2021 Apr 24.
Autistic traits are highly heritable and characterized by social deficits. Common genetic variants of the autism-related CNTNAP2 gene have been linked with social impairments, but the neural substrates are poorly understood. In the present study, we investigated the genetic effect of common variants of CNTNAP2 (rs2710102 and rs7794745) on gray matter volume and its association with social performance among 442 healthy participants. Our results showed that individuals with rs2710102 GG homozygotes had smaller left superior temporal gyrus (STG)/insular volume than A-allele carriers (AA and AG), while individuals with rs7794745 TT and AT showed smaller right parahippocampal, right STG/insular, and left inferior parietal lobule (IPL) cortex volume than those with rs7794745 AA. Smaller volume of the STG/insular and parahippocampal cortex was associated with poorer social performance. An indirect effect of CNTNAP2 rs7794745 and rs2710102 genotype on the social performance was mediated by the STG/insular cortex and parahippocampal cortex volume. These findings provided insight into the genetic effect of CNTNAP2 variants on social behavior, which may be moderated by the temporal cortex.
自闭症特征具有高度遗传性，其特征为社交缺陷。与自闭症相关的 CNTNAP2 基因的常见遗传变异与社交障碍有关，但神经基础知之甚少。在本研究中，我们研究了 CNTNAP2（rs2710102 和 rs7794745）常见变体的遗传效应对 442 名健康参与者的大脑灰质体积及其与社交表现的关联。结果表明，与 rs2710102 的 AA 和 AG 携带者相比，GG 纯合子个体的左侧颞上回（STG）/岛叶体积较小，而 TT 和 AT 携带者的右侧海马旁回、右侧 STG/岛叶和左侧顶下小叶（IPL）皮质体积较小。STG/岛叶和海马旁回皮质体积较小与社交表现较差相关。CNTNAP2 rs7794745 和 rs2710102 基因型对社会表现的间接影响可通过 STG/岛叶皮质和海马旁回皮质体积来介导。这些发现深入了解了 CNTNAP2 变体对社会行为的遗传影响，这种影响可能受到颞叶的调节。
