Genome-wide association and interaction studies of CSF T-tau/Aβ42 ratio in ADNI cohort

NEUROBIOLOGY OF AGING

卷:57

Article

Li, Jin¹  Zhang, Qiushi^1,2  Chen, Feng¹  Meng, Xianglian¹  Liu, Wenjie¹  Chen, Dandan^1,2  Yan, Jingwen^3,4,5  Kim, Sungeun³  Wang, Lei¹  Feng, Weixing¹  Saykin, Andrew J.³  Liang, Hong¹  Shen, Li^3,4,5 

[1] Harbin Engn Univ, Coll Automat, 145 Nantong St, Harbin 15000, Peoples R China

[2] Northeast Dianli Univ, Coll Informat Engn, Jilin, Jilin, Peoples R China

[3] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, 355 West 16th St,Suite 4100, Indianapolis, IN 46202 USA

[4] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA

[5] Indiana Univ, Sch Informat & Comp, Dept BioHlth Informat, Indianapolis, IN 46204 USA

关键词: Cerebrospinal fluid (CSF);    Amyloid-beta(42) (A beta(42));    Total tau (T-tau);    T-tau/A beta(42) ratio;    GWIS;    ADNI;   

DOI  :  10.1016/j.neurobiolaging.2017.05.007

来源: Elsevier

【 摘 要 】

The pathogenic relevance in Alzheimer's disease (AD) presents a decrease of cerebrospinal fluid amyloid beta(42) (A beta(42)) 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/A beta(42) 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/A beta(42), demonstrating their potential association with AD pathology. (C) 2017 Elsevier Inc. All rights reserved.

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