Department of Gynecology, Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Department of Pediatrics, The University of Texas MD Anderson Cancer center, Houston, Texas, USA.
Sci Rep. 2018 May 23;8(1):8068. doi: 10.1038/s41598-018-26398-1.
Some studies have demonstrated interactions of AD-risk single nucleotide polymorphisms (SNPs) in non-APOE regions with APOE genotype. Nevertheless, no study reported interactions of expression quantitative trait locus (eQTL) for APOE with APOE genotype. In present study, we included 9286 unrelated AD patients and 8479 normal controls from 12 cohorts of NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). 34 unrelated brain eQTLs for APOE were compiled from BRAINEAC and GTEx. We used multi-covariate logistic regression analysis to identify eQTLs interacted with APOE ε4. Adjusted for age and gender, substantia nigra eQTL rs438811 for APOE showed significantly strong interaction with APOE ε4 status (OR, 1.448; CI, 1.124-1.430; P-value = 7.94 × 10). APOE ε4-based sub-group analyses revealed that carrying one minor allele T of rs438811 can increase the opportunity of developing to AD by 26.75% in APOE ε4 carriers but not in non-carriers. We revealed substantia nigra eQTL rs438811 for APOE can interact with APOE ε4 and confers risk in APOE ε4 carriers only.
一些研究表明，非 APOE 区域的 AD 风险单核苷酸多态性 (SNP) 与 APOE 基因型存在相互作用。然而，尚无研究报道 APOE 表达数量性状基因座 (eQTL) 与 APOE 基因型之间存在相互作用。在本研究中，我们纳入了来自 NIA 遗传学阿尔茨海默病数据存储库 (NIAGADS) 和阿尔茨海默病神经影像学倡议 (ADNI) 的 12 个队列的 9286 名无关 AD 患者和 8479 名正常对照。从 BRAINEAC 和 GTEx 中汇编了 34 个与 APOE 无关的脑 eQTL。我们使用多协变量逻辑回归分析来识别与 APOE ε4 相互作用的 eQTL。在调整年龄和性别后，APOE 的 substantia nigra eQTL rs438811 与 APOE ε4 状态显示出显著的强相互作用（OR，1.448；CI，1.124-1.430；P 值 = 7.94 × 10）。基于 APOE ε4 的亚组分析显示，携带 rs438811 的一个次要等位基因 T 可以使 APOE ε4 携带者患 AD 的机会增加 26.75%，而在非携带者中则不会。我们揭示了 APOE 的 substantia nigra eQTL rs438811 可以与 APOE ε4 相互作用，并且仅在 APOE ε4 携带者中赋予风险。
