Associations of NPPA promoter true methylation and hydroxymethylation with ischemic stroke and its functional outcome

Background
Atrial natriuretic peptide (ANP) has been associated with ischemic stroke (IS), but the underlying molecular mechanisms are not clear. The objective of this study was to examine whether DNA methylation and hydroxymethylation in the coding gene of ANP (NPPA) were associated with IS, as well as its functional outcome.
Methods and Results
DNA methylation and hydroxymethylation in NPPA promoter region were quantified by targeted bisulfite sequencing and APOBEC-coupled epigenetic sequencing, respectively, in 615 IS patients and 610 age- and sex-matched healthy controls. True methylation was calculated as the quantified methylation level minus the quantified hydroxymethylation level. The functional outcome of IS was evaluated by the modified Rankin Scale (mRS) at a 3-month follow-up visit after onset. Multiple testing was controlled by the false discovery rate approach. Of the nine CpG sites assayed, hypomethylation at eight CpGs was not only associated with an increased risk of ha..., , , # Associations of NPPA Promoter True Methylation and Hydroxymethylation with Ischemic Stroke and Its Functional Outcome

[https://doi.org/10.5061/dryad.h18931zvn](https://doi.org/10.5061/dryad.h18931zvn)

## Description of the data and file structure

DNA methylation and hydroxymethylation in *NPPA* promoter region were quantified by targeted bisulfite sequencing and APOBEC-coupled epigenetic sequencing, respectively, in 615 IS patients and 610 age- and sex-matched healthy controls. True methylation was calculated as the quantified methylation level minus the quantified hydroxymethylation level.

### Files and variables

#### File: NPPA\_hmc.csv

**Description:**  Hydroxymethylation levels at 9 CpG sites in the promoter region of NPPA gene，the unit of Hydroxymethylation is %.

##### Variables

* CpG site: genetic location of the CpG site
* Chr: Chromsome
* Distance2TSS: Distance to transcription site
* GenomePosition: genome position
* Position: functional position
* Target: the target ...

**背景**：心房利钠肽（Atrial natriuretic peptide, ANP）与缺血性脑卒中（ischemic stroke, IS）已被证实存在关联，但其潜在分子机制仍未明确。本研究旨在探讨ANP编码基因NPPA的DNA甲基化（DNA methylation）与羟甲基化（hydroxymethylation）水平是否与IS及其功能预后相关。

**方法与结果**：本研究纳入615名IS患者与610名年龄、性别匹配的健康对照，分别采用靶向亚硫酸氢盐测序（targeted bisulfite sequencing）与APOBEC偶联表观基因组测序（APOBEC-coupled epigenetic sequencing）对NPPA启动子区域的DNA甲基化与羟甲基化水平进行定量检测。真实甲基化水平通过定量得到的甲基化水平减去定量羟甲基化水平计算得出。IS患者的功能预后于发病后3个月随访时采用改良Rankin量表（modified Rankin Scale, mRS）进行评估。多重检验通过错误发现率（false discovery rate）方法进行校正。本研究检测的9个CpG位点（CpG site）中，8个CpG位点的低甲基化不仅与脑卒中风险升高相关……[原文未完整展示]。

# NPPA启动子真实甲基化与羟甲基化水平与缺血性脑卒中及其功能预后的关联
[https://doi.org/10.5061/dryad.h18931zvn]

**数据与文件结构说明**：本研究分别通过靶向亚硫酸氢盐测序与APOBEC偶联表观基因组测序，对615名IS患者与610名年龄、性别匹配的健康对照的NPPA启动子区域DNA甲基化与羟甲基化水平进行定量检测。真实甲基化水平由定量甲基化水平减去定量羟甲基化水平计算得到。

### 文件与变量
#### 文件：NPPA_hmc.csv
**描述**：NPPA基因启动子区域9个CpG位点（CpG site）的羟甲基化水平，羟甲基化单位为%。
##### 变量：
* CpG位点（CpG site）：CpG位点的遗传定位信息
* Chr：染色体
* Distance2TSS：距转录起始位点的距离
* GenomePosition：基因组位置
* Position：功能位点位置
* Target：靶标……[原文未完整展示]