A scoring strategy combining statistics and functional genomics supports a possible role for common polygenic variation in autism.
A scoring strategy combining statistics and functional genomics supports a possible role for common polygenic variation in autism.
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DOI：
10.3389/fgene.2014.00033
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发表时间：
2014
影响因子：
3.7
通讯作者：
Rio Frio T
中科院分区：
文献类型：
--
作者：
Carayol J;Schellenberg GD;Dombroski B;Amiet C;Génin B;Fontaine K;Rousseau F;Vazart C;Cohen D;Frazier TW;Hardan AY;Dawson G;Rio Frio T
自闭症谱系障碍（ASD）是一种高度遗传的复杂神经发育障碍，男女比例为4：1。常见的遗传变异可以解释40-60%的自闭症易感性差异。由于它们的影响很小，全基因组关联研究（GWAS）只确定了少量的单个单核苷酸多态性（SNP）。为了提高GWAS在复杂疾病中的作用，出现了融合功能基因组学（CFG）等方法，可以从噪声中提取真正的关联信号，并使用统计学和功能基因组学相结合的评分策略从SNP中识别和优先考虑基因。我们改编并应用这种方法来分析来自自闭症遗传资源交换（AGRE）的多个自闭症儿童家庭的GWAS数据。我们从发现人群中鉴定了一组133个候选标记，这些标记位于ASD中与功能相关的基因中或附近（545个多重家庭）;基于这些常见变异的性别特异性遗传评分（GS）解释了1%（男性P = 0.01）和5%（女性P = 8.7 × 10−7）的遗传变异。总的来说，我们的工作表明，基于功能基因组学的GWAS数据的优先级确定了与自闭症相关的常见变异，并为自闭症的常见多基因背景提供了额外的支持。
Autism spectrum disorders (ASD) are highly heritable complex neurodevelopmental disorders with a 4:1 male: female ratio. Common genetic variation could explain 40–60% of the variance in liability to autism. Because of their small effect, genome-wide association studies (GWASs) have only identified a small number of individual single-nucleotide polymorphisms (SNPs). To increase the power of GWASs in complex disorders, methods like convergent functional genomics (CFG) have emerged to extract true association signals from noise and to identify and prioritize genes from SNPs using a scoring strategy combining statistics and functional genomics. We adapted and applied this approach to analyze data from a GWAS performed on families with multiple children affected with autism from Autism Speaks Autism Genetic Resource Exchange (AGRE). We identified a set of 133 candidate markers that were localized in or close to genes with functional relevance in ASD from a discovery population (545 multiplex families); a gender specific genetic score (GS) based on these common variants explained 1% (P = 0.01 in males) and 5% (P = 8.7 × 10−7 in females) of genetic variance in an independent sample of multiplex families. Overall, our work demonstrates that prioritization of GWAS data based on functional genomics identified common variants associated with autism and provided additional support for a common polygenic background in autism.
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影响因子：
14.9
作者：
Blake JA;Bult CJ;Kadin JA;Richardson JE;Eppig JT;Mouse Genome Database Group
通讯作者：
Mouse Genome Database Group
影响因子：
64.8
作者：
Cook, Edwin H., Jr.;Scherer, Stephen W.
通讯作者：
Scherer, Stephen W.
影响因子：
4
作者：
Ben-Shachar S;Lanpher B;German JR;Qasaymeh M;Potocki L;Nagamani SC;Franco LM;Malphrus A;Bottenfield GW;Spence JE;Amato S;Rousseau JA;Moghaddam B;Skinner C;Skinner SA;Bernes S;Armstrong N;Shinawi M;Stankiewicz P;Patel A;Cheung SW;Lupski JR;Beaudet AL;Sahoo T
通讯作者：
Sahoo T
影响因子：
12.3
作者：
Carroll LS;Owen MJ
通讯作者：
Owen MJ
影响因子：
6.9
作者：
BAILEY, A;LECOUTEUR, A;RUTTER, M
通讯作者：
RUTTER, M