Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk
Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk
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DOI：
10.1186/2040-2392-1-4
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发表时间：
2010-01-01
期刊：
影响因子：
6.2
通讯作者：
Dawson, Geraldine
中科院分区：
文献类型：
--
作者：
Carayol, Jerome;Schellenberg, Gerard D.;Dawson, Geraldine
背景资料：自闭症是一种复杂的疾病，其特征是涉及沟通，社会互动以及重复和限制性行为模式的缺陷。双胞胎研究表明，自闭症具有很强的遗传性，这表明有很强的遗传成分。在具有复杂病因的其他疾病状态中，例如2型糖尿病，癌症和心血管疾病，遗传评分中多种遗传变异的组合分析有助于识别疾病高风险个体。遗传评分的目的是测试与疾病的遗传标记的关联。方法：多个风险等位基因的积累显着增加的风险受到影响，并与单独研究多态性相比，它提高了识别亚组的个人在更大的风险。在目前的研究中，我们表明，这种方法可以应用于自闭症，特别是在一个高风险的儿童人群谁有自闭症的兄弟姐妹。一个双样本的研究设计和使用多个独立的基因的遗传评分的生成被用来评估自闭症的风险在高危population.Results：在这两个样本中，优势比（OR）显着增加的风险等位基因的数量的函数，与8的遗传评分与OR为5.54（95%置信区间[CI] 2.45至12.49）。在两种分析中，每个遗传评分的敏感性和特异性是相似的，并且所得到的受试者工作特征曲线下的面积是相同的（0.59）.结论：这些结果表明，遗传评分中多个风险等位基因的积累是评估受影响个体的兄弟姐妹患自闭症风险的有用策略，并且可能比研究单个多态性更好地识别具有显著更大风险的个体亚组。
Background: Autism is a complex disorder characterized by deficits involving communication, social interaction, and repetitive and restrictive patterns of behavior. Twin studies have shown that autism is strongly heritable, suggesting a strong genetic component. In other disease states with a complex etiology, such as type 2 diabetes, cancer and cardiovascular disease, combined analysis of multiple genetic variants in a genetic score has helped to identify individuals at high risk of disease. Genetic scores are designed to test for association of genetic markers with disease.Method: The accumulation of multiple risk alleles markedly increases the risk of being affected, and compared with studying polymorphisms individually, it improves the identification of subgroups of individuals at greater risk. In the present study, we show that this approach can be applied to autism by specifically looking at a high-risk population of children who have siblings with autism. A two-sample study design and the generation of a genetic score using multiple independent genes were used to assess the risk of autism in a high-risk population.Results: In both samples, odds ratios (ORs) increased significantly as a function of the number of risk alleles, with a genetic score of 8 being associated with an OR of 5.54 (95% confidence interval [CI] 2.45 to 12.49). The sensitivities and specificities for each genetic score were similar in both analyses, and the resultant area under the receiver operating characteristic curves were identical (0.59).Conclusions: These results suggest that the accumulation of multiple risk alleles in a genetic score is a useful strategy for assessing the risk of autism in siblings of affected individuals, and may be better than studying single polymorphisms for identifying subgroups of individuals with significantly greater risk.