Genes Related to Sex Steroids, Neural Growth, and Social-Emotional Behavior are Associated with Autistic Traits, Empathy, and Asperger Syndrome
Genes Related to Sex Steroids, Neural Growth, and Social-Emotional Behavior are Associated with Autistic Traits, Empathy, and Asperger Syndrome
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DOI：
10.1002/aur.80
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发表时间：
2009-06-01
期刊：
影响因子：
4.7
通讯作者：
Baron-Cohen, S.
中科院分区：
文献类型：
--
作者：
Chakrabarti, B.;Dudbridge, F.;Baron-Cohen, S.
自闭症谱系条件（ASC）的遗传学研究主要集中在“低功能”的严重临床亚群上，将其视为一种罕见的疾病。然而，ASC现在被认为是相对常见的（接近1%），并且代表了一般人群中自闭症特征准正态分布的一端。在这里，我们报告了一项与自闭症特征和阿斯伯格综合征（AS）相关的候选基因的共同遗传变异的研究。我们在两个实验中测试了三个功能组（性类固醇合成/转运、神经连接和社会情绪反应）中68个候选基因的单核苷酸多态性。这些是(a)在人口样本（n = 349）中相关行为特征（共情商（EQ），自闭症谱系商（AQ））的关联研究；(b)对AS患者样本（ASC的“高功能”亚组）进行病例对照关联研究（n = 174）。27个基因显示与自闭症特征和/或ASC诊断有名义上的显著关联。其中19个基因与AQ/EQ有显著相关。在性类固醇组，这包括ESR2和CYP11B1。在神经连通性组，这包括HOXA1， NTRK1和NLGN4X。在社会反应性行为组，这包括MAOB、AVPR1B和WFS1。14个基因与AS有名义上显著的相关性。在性类固醇组，这包括CYP17A1和CYP19A1。在社会情绪行为组中，这包括OXT。六个基因在两个实验中名义上是相关的，提供了部分复制。在两个实验中，有11个基因通过排列修正了家庭明智错误率（FWER），这比偶然预期的要大。在两个实验中，经过EWER校正后，CYP11B1和NTRK1成为显著相关基因
Genetic studies of autism spectrum conditions (ASC) have mostly focused on the "low functioning" severe clinical subgroup, treating it as a rare disorder. However, ASC is now thought to be relatively common (similar to 1%), and representing one end of a quasi-normal distribution of autistic traits in the general population. Here we report a study of common genetic variation in candidate genes associated with autistic traits and Asperger syndrome (AS). We tested single nucleotide polymorphisms in 68 candidate genes in three functional groups (sex steroid synthesis/transport, neural connectivity, and social-emotional responsivity) in two experiments. These were (a) an association study of relevant behavioral traits (the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ) in a population sample (n = 349); and (b) a case-control association study on a sample of people with AS, a "high-functioning" subgroup of ASC (n = 174). 27 genes showed a nominally significant association with autistic traits and/or ASC diagnosis. Of these, 19 genes showed nominally significant association with AQ/EQ. In the sex steroid group, this included ESR2 and CYP11B1. In the neural connectivity group, this included HOXA1, NTRK1, and NLGN4X. In the socio-responsivity behavior group, this included MAOB, AVPR1B, and WFS1. Fourteen genes showed nominally significant association with AS. In the sex steroid group, this included CYP17A1 and CYP19A1. In the socio-emotional behavior group, this included OXT. Six genes were nominally associated in both experiments, providing a partial replication. Eleven genes survived family wise error rate (FWER) correction using permutations across both experiments, which is greater than would be expected by chance. CYP11B1 and NTRK1 emerged as significantly associated genes in both experiments, after EWER correction (P