Autism specific patterns of DNA methylation from birth to age 5

从出生到 5 岁的自闭症特定 DNA 甲基化模式

基本信息

  • 批准号:
    10056789
  • 负责人:
  • 金额:
    $ 26.14万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-07 至 2022-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects up to 2% of U.S. children. ASD disabilities have substantial adverse impacts on individuals living with ASD and their families and communities. The estimated annual cost of ASD related disabilities exceeds $250 billion. Recent findings have shown that early detection and intervention can minimize the impact of ASD disabilities, maximize children’s developmental potential, and ultimately improve long-term outcomes. However, no reliable markers currently exist to detect ASD in children under the age of 24 months and the mean age of ASD diagnosis still hovers around age 5. The goal of this study is to address this critical need by evaluating whether early life DNA methylation (DNAm) patterns in blood reflect later ASD diagnosis. Previous studies, by us and others, have found DNAm changes in older children and adults with an ASD diagnosis. However, it isn’t clear whether these differences are present during infancy and may serve as an early life ASD risk biomarker. In addition, despite strong evidence for epigenetic links to ASD most studies have focused on identifying specific loci related to ASD - only one study considered changes in the epigenetic aging pathway and none to our knowledge have examined global DNAm changes related to ASD. Finally, no studies have tested for longitudinal changes in DNAm related to ASD. Here, we overcome previous study limitations by leveraging a unique US population-based study of ASD with infant heal-stick cards (pre- diagnosis) and blood collected at age 5 (post-diagnosis). This enables us to assess prospective and longitudinal DNAm associations with ASD. We use extant (n=968) and newly generated DNAm data on 210 subjects to test our hypotheses that infant blood DNAm patterns are related to later ASD diagnoses and that longitudinal DNAm changes occur concomitant with the emergence of ASD signs. Using samples collected near birth and again at age 5, we will estimate differences: (1A) in heal-stick blood spot DNAm at birth and (1B) in longitudinal DNAm patterns from birth to age 5 between children with and without an ASD diagnosis at age 5. In Aim 2, we will test for epigenetic age acceleration/deceleration: (2A) at birth, and (2B) longitudinally from birth to age 5 between children with and without an ASD diagnosis at age 5. Any significant associations will undergo secondary analyses to test whether the identified DNAm changes are specific to ASD or are also present in SEED children with other developmental disabilities. This R21 mechanism provides the early conceptual support needed to determine whether this area of research warrants further examination in a larger sample, which could include ~4,000 SEED samples. The results of this study may, ultimately, impact child health by providing an early life DNA methylation marker of ASD risk to inform future intervention strategies. Further, the dynamic DNAm changes we identify during early life will likely be important for other childhood health outcomes, more broadly.
项目摘要 自闭症谱系障碍(ASD)是一种神经发育疾病,影响多达2%的美国儿童。 ASD残疾对ASD患者及其家庭有很大的不利影响, 社区. ASD相关残疾的估计年度成本超过2500亿美元。最近的调查结果表明, 早期发现和干预可以最大限度地减少ASD残疾的影响, 发展潜力,并最终改善长期结果。然而,目前没有可靠的标记 在24个月以下的儿童中检测ASD存在,并且ASD诊断的平均年龄仍然徘徊 大概5岁这项研究的目的是通过评估早期生命DNA是否 血液中的DNA甲基化(DNAm)模式反映了后来的ASD诊断。 我们和其他人以前的研究发现,患有ASD的年龄较大的儿童和成人的DNA m发生了变化 诊断.然而,目前尚不清楚这些差异是否存在于婴儿期,并可能作为一个 早期生活ASD风险生物标志物。此外,尽管有强有力的证据表明表观遗传与ASD有关,但大多数研究 一直专注于确定与ASD相关的特定基因座-只有一项研究考虑了表观遗传学的变化, 衰老途径,但据我们所知,还没有人研究过与ASD相关的全球DNA变化。终于没有 研究已经测试了与ASD相关的DNA m的纵向变化。在这里,我们克服了以前的研究 通过利用独特的美国人群为基础的ASD研究与婴儿健康棒卡(前, 诊断)和在5岁时(诊断后)收集的血液。这使我们能够评估未来和 与ASD的纵向DNAm关联。我们使用现存的(n=968)和新生成的DNAm数据210 受试者来检验我们的假设,即婴儿血液DNAm模式与后来的ASD诊断有关, 纵向DNAm变化伴随ASD体征的出现而发生。使用采集的样本 在出生前和5岁时,我们将估计差异:(1A)出生时的healstick血斑DNAm, (1B)从出生到5岁,ASD诊断儿童和非ASD诊断儿童之间的纵向DNAm模式, 5岁。在目标2中,我们将测试表观遗传年龄加速/减速:(2A)出生时,(2B)纵向 从出生到5岁,在5岁时有ASD诊断和没有ASD诊断的儿童之间。有什么重要的关联吗 将进行二次分析,以测试所识别的DNAm变化是否是ASD特异性的,或者也是 存在于SEED儿童中的其他发育障碍。 这一R21机制提供了确定这一领域是否 研究需要在更大的样本中进行进一步检查,其中可能包括约4,000个SEED样本。的 这项研究的结果可能最终通过提供一种早期生命DNA甲基化标记物来影响儿童健康, ASD风险为未来的干预策略提供信息。此外,我们在早期发现的动态DNAm变化 更广泛地说,生命可能对其他儿童健康结果很重要。

项目成果

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Christine Ladd-Acosta其他文献

Christine Ladd-Acosta的其他文献

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{{ truncateString('Christine Ladd-Acosta', 18)}}的其他基金

GEARs Combining advances in Genomics and Environmental science to accelerate Actionable Research and practice in ASD
GEARs 结合基因组学和环境科学的进步,加速 ASD 的可操作研究和实践
  • 批准号:
    10698145
  • 财政年份:
    2022
  • 资助金额:
    $ 26.14万
  • 项目类别:
GEARs Combining advances in Genomics and Environmental science to accelerate Actionable Research and practice in ASD
GEARs 结合基因组学和环境科学的进步,加速 ASD 的可操作研究和实践
  • 批准号:
    10523737
  • 财政年份:
    2022
  • 资助金额:
    $ 26.14万
  • 项目类别:
The role of epigenetics in the adverse effects of social environmental stressors on COPD outcomes
表观遗传学在社会环境压力因素对慢性阻塞性肺病结局的不利影响中的作用
  • 批准号:
    10551798
  • 财政年份:
    2021
  • 资助金额:
    $ 26.14万
  • 项目类别:
The role of epigenetics in the adverse effects of social environmental stressors on COPD outcomes
表观遗传学在社会环境压力因素对慢性阻塞性肺病结局的不利影响中的作用
  • 批准号:
    10392320
  • 财政年份:
    2021
  • 资助金额:
    $ 26.14万
  • 项目类别:
Study to Explore Early Development (SEED) Follow up Studies, Components A, B, D & E
探索早期发育的研究 (SEED) 后续研究,组成部分 A、B、D
  • 批准号:
    10633217
  • 财政年份:
    2021
  • 资助金额:
    $ 26.14万
  • 项目类别:
The role of epigenetics in the adverse effects of social environmental stressors on COPD outcomes
表观遗传学在社会环境压力因素对慢性阻塞性肺病结局的不利影响中的作用
  • 批准号:
    10052092
  • 财政年份:
    2021
  • 资助金额:
    $ 26.14万
  • 项目类别:

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