The pathogenic relevance in Alzheimer's disease (AD) presents a decrease of cerebrospinal fluid amyloid-ß42 (Aß42) burden and an increase in cerebrospinal fluid total tau (T-tau) levels. In this work, we performed genome-wide association study (GWAS) and genome-wide interaction study of T-tau/Aß42 ratio as an AD imaging quantitative trait on 843 subjects and 563,980 single-nucleotide polymorphisms (SNPs) in ADNI cohort. We aim to identify not only SNPs with significant main effects but also SNPs with interaction effects to help explain "missing heritability". Linear regression method was used to detect SNP-SNP interactions among SNPs with uncorrected p-value ≤0.01 from the GWAS. Age, gender, and diagnosis were considered as covariates in both studies. The GWAS results replicated the previously reported AD-related genes APOE, APOC1, and TOMM40, as well as identified 14 novel genes, which showed genome-wide statistical significance. Genome-wide interaction study revealed 7 pairs of SNPs meeting the cell-size criteria and with bonferroni-corrected p-value ≤0.05. As we expect, these interaction pairs all had marginal main effects but explained a relatively high-level variance of T-tau/Aß42, demonstrating their potential association with AD pathology.

译文

阿尔茨海默氏病 (AD) 的致病相关性表明脑脊液淀粉样蛋白42 (a ß 42) 负担减少,脑脊液总tau (T-tau) 水平增加。在这项工作中,我们对843受试者进行了全基因组关联研究 (GWAS) 和全基因组相互作用研究,研究T-tau/a ß 42比率作为AD成像定量性状,并在ADNI队列中563,980单核苷酸多态性 (snp)。我们的目标是不仅确定具有显着主效应的snp,而且还确定具有相互作用效应的snp,以帮助解释 “缺失遗传力”。线性回归方法用于检测来自GWAS的p值 ≤ 0.01的SNP之间的SNP-SNP相互作用。在两项研究中,年龄、性别和诊断均被视为协变量。GWAS结果复制了先前报道的AD相关基因APOE,APOC1和tom40,并鉴定了14个新基因,这些新基因显示了全基因组的统计意义。全基因组相互作用研究揭示了7对符合细胞大小标准且bonferroni校正的p值 ≤ 0.05的snp。正如我们所期望的那样,这些相互作用对都具有边际主效应,但解释了T-tau/a ß 42的相对高水平方差,表明它们与AD病理的潜在关联。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录