Circulating biomarkers of immunity and inflammation, risk of Alzheimer's disease, and hippocampal volume: a Mendelian randomization study.
Circulating biomarkers of immunity and inflammation, risk of Alzheimer's disease, and hippocampal volume: a Mendelian randomization study.
复制标题
免疫和炎症的循环生物标志物，阿尔茨海默氏病风险和海马体积：孟德尔随机研究。
DOI：
10.1038/s41398-021-01400-z
复制
发表时间：
2021-05-17
影响因子：
6.8
通讯作者：
Dichgans M
中科院分区：
文献类型：
--
作者：
Fani L;Georgakis MK;Ikram MA;Ikram MK;Malik R;Dichgans M
本研究的目的是通过进行两样本孟德尔随机研究，探讨基因预测的免疫和炎症循环水平与阿尔茨海默病 (AD) 风险和海马体积之间的关联。我们确定了 12 种免疫细胞标记物和衍生比率（血小板计数、嗜酸性粒细胞计数、中性粒细胞计数、嗜碱性粒细胞计数、单核细胞计数、淋巴细胞计数、血小板与淋巴细胞比率、单核细胞与淋巴细胞比率、CD4 计数、CD8 计数、CD4-CD8 比率和 CD56）和 5 种信号分子（IL-6、纤维蛋白原、CRP 和 Lp-PLA2 活性和质量）作为主要利益暴露。其他与 AD 的先验联系较弱的遗传性免疫生物标志物被认为是二次暴露。国际阿尔茨海默病基因组学项目 (IGAP) GWAS 数据集（21,982 例病例；41,944 名欧洲血统对照）评估了与 AD 的关联。对于海马体积，我们从 33,536 名欧洲血统参与者的 GWAS 荟萃分析中提取了数据。使用错误发现率 < 5%（Q值 < 0.05）进行多重比较的P值校正后，初级或次级暴露均未显示出与AD或海马体积具有统计学显着相关性。 CD4 计数与 AD 的关联性最强（比值比 1.32，P < 0.01，Q > 0.05）。通过 Cochran Q 测量的 MR 逆方差加权荟萃分析以及多次暴露的加权中值和加权模式有证据表明存在异质性。进一步的聚类分析没有揭示可能以不同方式影响风险因素的变异聚类。这项研究表明，基因预测的免疫和炎症循环生物标志物与 AD 风险或海马体积无关。未来的研究应该评估竞争风险，更深入地探索适应性免疫在 AD 中的作用，特别是 T 细胞和 CD4 亚型，并在其他种族中证实这些发现。
The aim of this study was to explore the association between genetically predicted circulating levels of immunity and inflammation, and the risk of Alzheimer’s disease (AD) and hippocampal volume, by conducting a two-sample Mendelian Randomization Study. We identified 12 markers of immune cells and derived ratios (platelet count, eosinophil count, neutrophil count, basophil count, monocyte count, lymphocyte count, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, CD4 count, CD8 count, CD4-to-CD8 ratio, and CD56) and 5 signaling molecules (IL-6, fibrinogen, CRP, and Lp-PLA2 activity and mass) as primary exposures of interest. Other genetically available immune biomarkers with a weaker a priori link to AD were considered secondary exposures. Associations with AD were evaluated in The International Genomics of Alzheimer’s Project (IGAP) GWAS dataset (21,982 cases; 41,944 controls of European ancestry). For hippocampal volume, we extracted data from a GWAS meta-analysis on 33,536 participants of European ancestry. None of the primary or secondary exposures showed statistically significant associations with AD or with hippocampal volume following P-value correction for multiple comparisons using false discovery rate < 5% (Q-value < 0.05). CD4 count showed the strongest suggestive association with AD (odds ratio 1.32, P < 0.01, Q > 0.05). There was evidence for heterogeneity in the MR inverse variance-weighted meta-analyses as measured by Cochran Q, and weighted median and weighted mode for multiple exposures. Further cluster analyses did not reveal clusters of variants that could influence the risk factor in distinct ways. This study suggests that genetically predicted circulating biomarkers of immunity and inflammation are not associated with AD risk or hippocampal volume. Future studies should assess competing risk, explore in more depth the role of adaptive immunity in AD, in particular T cells and the CD4 subtype, and confirm these findings in other ethnicities.
登录
查看更多内容
影响因子：
7.7
作者：
Burgess S
通讯作者：
Burgess S
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
2.1
作者：
Anand, Akshay;Banik, Avijit;Masters, Colin L.
通讯作者：
Masters, Colin L.
影响因子：
9.8
作者：
Ahola-Olli, Ari V.;Wurtz, Peter;Raitakari, Olli T.
通讯作者：
Raitakari, Olli T.
影响因子：
64.5
作者：
Astle, William J.;Elding, Heather;Soranzo, Nicole
通讯作者：
Soranzo, Nicole