Division of Biostatistics, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 11461.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7073-7076. doi: 10.1073/pnas.1700439114. Epub 2017 Jun 19.
We develop a method of analysis [affected to discordant sibling pairs (A2DS)] that tests if shared variants contribute to a disorder. Using a standard measure of genetic relation, test individuals are compared with a cohort of discordant sibling pairs (CDS) to derive a comparative similarity score. We ask if a test individual is more similar to an unrelated affected than to the unrelated unaffected sibling from the CDS and then, sum over such individuals and pairs. Statistical significance is judged by randomly permuting the affected status in the CDS. In the analysis of published genotype data from the Simons Simplex Collection (SSC) and the Autism Genetic Resource Exchange (AGRE) cohorts of children with autism spectrum disorder (ASD), we find strong statistical significance that the affected are more similar to the affected than to the unaffected of the CDS ( value ∼ 0.00001). Fathers in multiplex families have marginally greater similarity ( value = 0.02) to unrelated affected individuals. These results do not depend on ethnic matching or gender.
我们开发了一种分析方法[受影响的不相关同胞对（A2DS）]，用于测试共享变体是否导致疾病。使用遗传关系的标准衡量标准，将测试个体与不相关的同胞对（CDS）进行比较，以得出比较相似性得分。我们询问测试个体与 CDS 中的无关受影响个体相比是否与不相关的未受影响的同胞更相似，然后对这些个体和对进行求和。通过在 CDS 中随机置换受影响的状态来判断统计显着性。在对自闭症谱系障碍（ASD）儿童的 Simons Simplex Collection（SSC）和 Autism Genetic Resource Exchange（AGRE）队列的已发表基因型数据进行分析时，我们发现受影响的个体与 CDS 的受影响个体比未受影响的个体更相似（ 值 ∼ 0.00001），具有很强的统计学意义。多基因家族的父亲与无关的受影响个体的相似性略有增加（ 值= 0.02）。这些结果不依赖于种族匹配或性别。
