Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry.
Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry.
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DOI：
10.1186/2040-2392-1-7
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发表时间：
2010-03-25
期刊：
影响因子：
6.2
通讯作者：
International Molecular Genetic Study of Autism Consortium (IMGSAC)
中科院分区：
文献类型：
--
作者：
Sousa I;Clark TG;Holt R;Pagnamenta AT;Mulder EJ;Minderaa RB;Bailey AJ;Battaglia A;Klauck SM;Poustka F;Monaco AP;International Molecular Genetic Study of Autism Consortium (IMGSAC)
自闭症谱系障碍（ASD）是一组高度遗传的神经发育障碍，其特征是由社交，沟通和限制兴趣/行为的障碍组成。几种细胞粘附跨膜富含亮氨酸重复序列（LRR）蛋白在神经系统中高度表达，并被认为是其发育的关键调节因子。在这里，我们提出了一项关联研究，分析了四个有希望的候选基因-LRRTM 1（2 p），LRRTM 3（10 q），LRRN 1（3 p）和LRRN 3（7 q）-的作用，以确定ASD的常见遗传风险因素。为了更好地了解这四个基因区域内的遗传变异如何影响ASD的易感性，在从四个不同ASD队列中选择的661个欧洲血统家庭中进行了一项基于家庭的关联研究。此外，还对4个LRR基因进行了病例对照研究，使用逻辑回归分析每个人群中ASD先证者与295名ECACC对照。采用单基因座和单倍型方法，发现LRRN 3和LRRTM 3的显著结果（P < 0.005）。这些结果得到了病例对照分析的进一步支持，该分析还强调了LRRTM 3中的其他SNP。总的来说，我们的研究结果暗示神经元富含亮氨酸的基因LRRN 3和LRRTM 3在ASD易感性。
Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs. In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls. Significant results were found for LRRN3 and LRRTM3 (P < 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in LRRTM3. Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1734197100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Aubert, J;Stavridis, MP;Smith, A
通讯作者：
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