基因风险：阿尔茨海默病的多基因风险评分
GenoRisk: A polygenic risk score for Alzheimer's disease.
作者信息
Dickson Samuel P, Hendrix Suzanne B, Brown Bruce L, Ridge Perry G, Nicodemus-Johnson Jessie, Hardy Marci L, McKeany Allison M, Booth Steven B, Fortna Ryan R, Kauwe John S K
机构信息
Pentara Corporation Salt Lake City Utah USA.
Department of Psychology Brigham Young University Provo Utah USA.
出版信息
Alzheimers Dement (N Y). 2021 Sep 30;7(1):e12211. doi: 10.1002/trc2.12211. eCollection 2021.
INTRODUCTION
Recent clinical trials are considering inclusion of more than just apolipoprotein E () ε4 genotype as a way of reducing variability in analysis of outcomes.
METHODS
Case-control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)-associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross-validation. Genotype and sex × age estimates from the best performing model were combined with age and intercept estimates from the general population to develop a personalized genetic risk score, termed age, and sex-adjusted GenoRisk.
RESULTS
The elastic net model that included age, age x sex interaction, allelic terms, and 29 additional SNPs performed the best. This model explained an additional 19% of the heritable risk compared to genotype alone and achieved an area under the curve of 0.747.
DISCUSSION
GenoRisk could improve the risk assessment of individuals identified for prevention studies.
引言
近期的临床试验正在考虑纳入除载脂蛋白E（）ε4基因型之外的更多因素，以此减少结果分析中的变异性。
方法
利用病例对照数据，通过几种统计模型比较年龄、性别和58种阿尔茨海默病（AD）相关单核苷酸多态性（SNP）预测AD状态的能力。使用布里尔评分和十折交叉验证评估模型性能。将表现最佳模型的基因型和性别×年龄估计值与来自一般人群的年龄和截距估计值相结合，以制定个性化遗传风险评分，称为年龄和性别调整后的基因风险（GenoRisk）。
结果
包含年龄、年龄×性别交互作用、等位基因项和另外29个SNP的弹性网络模型表现最佳。与仅使用基因型相比，该模型解释了额外19%的遗传风险，曲线下面积达到0.747。
讨论
基因风险（GenoRisk）可以改善为预防研究而确定的个体的风险评估。
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