多基因风险对22q11.2微删除的成年人身高和BMI的影响
Shengjie Ying1,2,3, Tracy Heung2,3, Bernice E Morrow4
1Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
Journal of the Endocrine Society
|July 31, 2025
概括
对身高和体重指数 (BMI) 的多基因风险评分 (PRS) 可以预测22q11.2微删除个体的生长特征. 高度PRS可能会改进患有这种遗传疾病的人的生长预期.
科学领域:
- 遗传学 是一个遗传学.
- 人类生物学 人类生物学
- 医学研究 医学研究
背景情况:
- 先验风险升高可以增加多基因风险评分 (PRS) 的临床效用.
- 22q11.2微切除与矮身和肥胖的风险增加有关.
研究的目的:
- 研究22q11.2微切除的个体中身高和BMI多基因风险评分 (PRS) 的修饰作用.
- 评估PRS在改进基因风险基线较高个体的生长预期方面的临床实用性.
主要方法:
- 在259名欧洲祖先的成年人中,测试了身高PRS和BMI-PRS与身高和BMI的关联,这些成年人有22q11.2微删除.
- 利用测序数据和多变量线性回归模型,考虑临床/人口学变量.
- 采用后勤回归和接收机运行特征曲线分析来预测矮身.
主要成果:
- 高度PRS和BMI-PRS分别解释了25.8%和5.7%的特征变异 (P < .001).
- 最低身高的PRS五分位数显示,与最高五分位数 (5.9%) 相比,身高矮的流行率 (42.3%) 显著更高.
- 结合身高PRS和共变量的模型实现了0.78的AUC来预测矮身,超过了仅使用共变量的模型.
结论:
- 全基因组的常见变异会影响成年人身高和BMI,而罕见的变异会导致先验风险升高.
- 高度PRS可以帮助精炼22q11.2微切除的个体的生长预期.
- 在复杂特征的遗传风险分层中,PRS显示出潜在的临床实用性.
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