Australian e-Health Research Centre, CSIRO, Floreat, Western Australia, 6014, Australia.
Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, 6027, Australia.
BMC Genomics. 2022 May 26;23(1):401. doi: 10.1186/s12864-022-08617-2.
With a growing number of loci associated with late-onset (sporadic) Alzheimer's disease (AD), the polygenic contribution to AD is now well established. The development of polygenic risk score approaches have shown promising results for identifying individuals at higher risk of developing AD, thereby facilitating the development of preventative and therapeutic strategies. A polygenic hazard score (PHS) has been proposed to quantify age-specific genetic risk for AD. In this study, we assessed the predictive power and transferability of this PHS in an independent cohort, to support its clinical utility.
Using genotype and imaging data from 780 individuals enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, we investigated associations between the PHS and several AD-related traits, including 1) cross-sectional Aβ-amyloid (Aβ) deposition, 2) longitudinal brain atrophy, 3) longitudinal cognitive decline, 4) age of onset. Except in the cognitive domain, we obtained results that were consistent with previously published findings. The PHS was associated with increased Aβ burden, faster regional brain atrophy and an earlier age of onset.
Overall, the results support the predictive power of a PHS, however, with only marginal improvement compared to apolipoprotein E alone.
随着越来越多与迟发性（散发性）阿尔茨海默病（AD）相关的基因座被发现，AD 的多基因贡献现在已得到充分证实。多基因风险评分方法的发展已显示出识别具有更高 AD 发病风险个体的有前途的结果，从而促进了预防和治疗策略的制定。多基因危害评分（PHS）已被提出用于量化 AD 的特定年龄的遗传风险。在这项研究中，我们评估了这种 PHS 在独立队列中的预测能力和可转移性，以支持其临床应用。
使用澳大利亚成像、生物标志物和生活方式（AIBL）研究中 780 名参与者的基因型和成像数据，我们研究了 PHS 与几种 AD 相关特征之间的关联，包括 1）横断面 Aβ-淀粉样蛋白（Aβ）沉积，2）纵向脑萎缩，3）纵向认知能力下降，4）发病年龄。除了认知领域外，我们得到的结果与先前发表的研究结果一致。PHS 与 Aβ负荷增加、更快的区域脑萎缩和更早的发病年龄相关。
总的来说，这些结果支持了 PHS 的预测能力，但与单独的载脂蛋白 E 相比，只有微小的改善。
