Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort
Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort
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DOI：
10.1093/ije/dyv028
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发表时间：
2015-08-01
影响因子：
7.7
通讯作者：
Feinberg, Andrew P.
中科院分区：
文献类型：
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作者：
Feinberg, Jason I.;Bakulski, Kelly M.;Feinberg, Andrew P.
背景：自Prader-Willi综合征(一种印迹障碍)与自闭症特征的经典关联开始，表观遗传学机制，如DNA甲基化改变，已被认为在自闭症中起作用。目的：在这里，我们测试了父亲精子DNA甲基化与子代自闭症风险的关系，调查了自闭症儿童父亲的丰富风险队列。方法：我们检测了来自自闭症谱系障碍(ASD)丰富风险妊娠队列的父亲精液基因组DNA甲基化(DNaM)，早期自闭症风险纵向调查(EARLI)队列，以评估d精子NAM与未来ASD发育之间的关联，使用12个月的ASD症状、评估、评估婴儿自闭症观察量表(AOSI)。我们分析了运行在Charm 3.0阵列上的44个精子样本的甲基化数据，该阵列包含400多万个探针(700多万个CpG位点)，其中30个样本也运行在Illumina Infinium Human Mylation450(450K)BeadChip平台上(类似于485,000个CpG位点)。我们还检查了死后人脑ASD的独立样本和对照样本中的相关区域，这些样本有Illumina 450K DNA甲基化数据。结果：使用基于区域的统计方法，我们用家族经验P值[家族错误率(FWER)]在父系精子中识别出193个差异甲基化区域(DMRS)。
Background: Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features.Objectives: Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children.Methods: We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (similar to 485 000 CpG sites). We also examined associated regions in an independent sample of postmortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available.Results: Using region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)]