He Jun, Cabrera-Mendoza Brenda, Friligkou Eleni, Mecca Adam P, van Dyck Christopher H, Pathak Gita A, Polimanti Renato
medRxiv. 2024 Jun 13:2024.06.12.24308850. doi: 10.1101/2024.06.12.24308850.
While higher socioeconomic factors (SEF) and cognitive performance (CP) have been associated with reduced Alzheimer's disease (AD) risk, recent evidence highlighted that these factors may have opposite effects on family history of AD (FHAD).
Leveraging data from the UK Biobank (N=448,100) and the All of Us Research Program (N=240,319), we applied generalized linear regression models, polygenic risk scoring (PRS), and one-sample Mendelian randomization (MR) to test the sex-specific SEF and CP associations with AD and FHAD.
Observational and genetically informed analyses highlighted that higher SEF and CP were associated with reduced AD and sibling-FHAD, while these factors were associated with increased parent-FHAD. We also observed that population minorities may present different patterns with respect to sibling-FHAD vs. parent-FHAD. Sex differences in FHAD associations were identified in ancestry-specific and SEF PRS and MR results.
This study contributes to understanding the sex-specific relationships linking SEF and CP to FHAD, highlighting the potential role of reporting, recall, and surviving-related dynamics.
虽然较高的社会经济因素（SEF）和认知能力（CP）与降低阿尔茨海默病（AD）风险有关，但最近的证据表明，这些因素可能对AD家族史（FHAD）产生相反的影响。
利用英国生物银行（N = 448,100）和“我们所有人”研究计划（N = 240,319）的数据，我们应用广义线性回归模型、多基因风险评分（PRS）和单样本孟德尔随机化（MR）来检验SEF和CP与AD及FHAD的性别特异性关联。
观察性分析和基于遗传信息的分析表明，较高的SEF和CP与降低AD及同胞FHAD风险有关，而这些因素与增加父母FHAD风险有关。我们还观察到，少数族裔在同胞FHAD与父母FHAD方面可能呈现不同模式。在特定血统和SEF的PRS及MR结果中发现了FHAD关联的性别差异。
本研究有助于理解将SEF和CP与FHAD联系起来的性别特异性关系，突出了报告、回忆和生存相关动态的潜在作用。
