Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children
Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children
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DOI：
10.1186/2040-2392-3-6
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发表时间：
2012-07-06
期刊：
影响因子：
6.2
通讯作者：
Chakrabarti, Bhismadev
中科院分区：
文献类型：
--
作者：
Tavassoli, Teresa;Auyeung, Bonnie;Chakrabarti, Bhismadev
背景：自闭症谱系疾病具有很强的遗传因素。非典型的感觉敏感性是自闭症谱系障碍的核心但被忽视的特征之一。GABRB3是自闭症谱系疾病的一个充分表征的候选基因。在小鼠中，杂合子Gabrb3缺失与触觉敏感性增加相关。然而，没有研究检查触觉敏感性是否与人类GABRB 3遗传变异有关。为了验证这一点，我们在普通人群中进行了两项试点遗传关联研究，分析了触觉敏感性的两种表型指标（父母报告和行为测量）与GABRB3中43个SNPs的关联。在两项触觉敏感度测量中，三个SNP（rs11636966、rs8023959和rs2162241）名义上与两种表型相关，提供了内部验证的测量。父母报告的得分与6个SNP名义上相关（P < 0.05）。行为测量的触觉敏感性名义上与10个SNP（三个Bonferroni校正后）。结论：这是第一个人类研究表明GABRB3变异和触觉敏感性之间的关联。这为来自动物模型的证据提供了支持，该证据暗示了GABRB3变异在自闭症谱系条件下的非典型感觉敏感性中的作用。未来的研究正在进行中，以直接测试自闭症谱系条件下的这种关联。
Background: Autism spectrum conditions have a strong genetic component. Atypical sensory sensitivities are one of the core but neglected features of autism spectrum conditions. GABRB3 is a well-characterised candidate gene for autism spectrum conditions. In mice, heterozygous Gabrb3 deletion is associated with increased tactile sensitivity. However, no study has examined if tactile sensitivity is associated with GABRB3 genetic variation in humans. To test this, we conducted two pilot genetic association studies in the general population, analysing two phenotypic measures of tactile sensitivity (a parent-report and a behavioural measure) for association with 43 SNPs in GABRB3.Findings: Across both tactile sensitivity measures, three SNPs (rs11636966, rs8023959 and rs2162241) were nominally associated with both phenotypes, providing a measure of internal validation. Parent-report scores were nominally associated with six SNPs (P < 0.05). Behaviourally measured tactile sensitivity was nominally associated with 10 SNPs (three after Bonferroni correction).Conclusions: This is the first human study to show an association between GABRB3 variation and tactile sensitivity. This provides support for the evidence from animal models implicating the role of GABRB3 variation in the atypical sensory sensitivity in autism spectrum conditions. Future research is underway to directly test this association in cases of autism spectrum conditions.