西非队列中血压特征的途径特定的多基因风险评分
Gregory Bormes1, Vanessa Robbin1, Tinashe Chikwore2,3
1Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
medRxiv : the preprint server for health sciences
|July 9, 2025
概括
路径特定的多基因风险评分 (PRS) 可以预测西非人的高血压风险. 然而,它们的预测能力有限,强调需要考虑其他遗传,环境和表观遗传因素.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 心血管疾病研究研究
- 药物基因组学 药物基因组学
背景情况:
- 全基因组多基因风险评分 (PRS) 有助于对高血压等多基因疾病的风险进行分层.
- 全基因组PRS的一个局限性是缺乏对生物途径风险分布的洞察力.
- 研究特定途径的PRS提供了对疾病风险遗传贡献的更细致的理解.
研究的目的:
- 评估特定路径的多基因风险评分 (PRS) 在预测高血压风险方面的有用性.
- 检查PRS在抗高血压治疗目标途径中的预测性表现.
- 分析西非队列中高血压风险分层,使用特定途径的PRS.
主要方法:
- 通过抗高血压药物向的11个生物通路 (1,149个基因) 被选择.
- 路径特定的PRS被计算为来自黑人高血压国际合作研究的2,395名高血压患者.
- 模型在分别为1,614个和966个人的单独队列中进行了验证和测试.
主要成果:
- 综合途径PRS改善了超越传统模型 (性别,年龄,主要成分) 的高血压风险预测.
- 包括PRS在内逐渐增加了静缩血压 (2.6%),静缩血压 (1.4%) 和平均动脉压 (1.1%) 的R平方.
- 特定的途径 (MAPK,cAMP,上腺体信号传递) 证明了通过透气血压和平均动脉压来分层个体的能力.
结论:
- 来自定义良好的遗传路径的路径特定的多基因风险得分可以预测非洲血统个体的高血压风险.
- 特定途径PRS的相对较低的可预测性强调了整合更广泛的遗传,环境和表观遗传因素的重要性.
- 需要进一步的研究,以捕捉超越路径特定的遗传贡献影响高血压风险的全部因素.
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