Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, 901 85, Umeå, Sweden.
Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
Sci Rep. 2022 Aug 2;12(1):13264. doi: 10.1038/s41598-022-17058-6.
PILRA (rs1859788 A > G) has been suggested to be a protective variant for Alzheimer's disease (AD) and is an entry co-receptor for herpes simplex virus-1. We conducted a nested case-control study of 360 1:1-matched AD subjects. Interactions between the PILRA-A allele, APOE risk variants (ε3/ε4 or ε4/ε4) and GM17 for AD risk were modelled. The associations were cross-validated using two independent whole-genome sequencing datasets. We found negative interactions between PILRA-A and GM17 (OR 0.72, 95% CI 0.52-1.00) and between PILRA-A and APOE risk variants (OR 0.56, 95% CI 0.32-0.98) in the discovery dataset. In the replication cohort, a joint effect of PILRA and PILRA × GM 17/17 was observed for the risk of developing AD (p .02). Here, we report a negative effect modification by PILRA on APOE and GM17 high-risk variants for future AD risk in two independent datasets. This highlights the complex genetics of AD.
PILRA(rs1859788 A>G) 被认为是阿尔茨海默病(AD)的保护性变异，是单纯疱疹病毒-1 的进入共受体。我们进行了一项 360 对 1:1 匹配的 AD 病例对照研究。模拟了 PILRA-A 等位基因、APOE 风险变体(ε3/ε4 或 ε4/ε4)和 GM17 之间对 AD 风险的相互作用。使用两个独立的全基因组测序数据集对关联进行了交叉验证。我们发现，在发现数据集中，PILRA-A 与 GM17 之间存在负相互作用(OR 0.72，95%CI 0.52-1.00)，PILRA-A 与 APOE 风险变体之间也存在负相互作用(OR 0.56，95%CI 0.32-0.98)。在复制队列中，PILRA 和 PILRA×GM17/17 的联合作用观察到 AD 发病风险增加(p<0.02)。在这里，我们在两个独立的数据集中报告了 PILRA 对 APOE 和 GM17 高风险变体未来 AD 风险的负效应修饰。这突出了 AD 的复杂遗传学。
