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

Jin Li, Qiushi Zhang, Feng Chen, Xianglian Meng, Wenjie Liu, Dandan Chen, Jingwen Yan, Sungeun Kim, Lei Wang, Weixing Feng, Andrew Saykin, Hong Liang, Li Shen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)247.e1-247.e8
JournalNeurobiology of Aging
Volume57
DOIs
StatePublished - Sep 1 2017

Fingerprint

Genome-Wide Association Study
Amyloid
Single Nucleotide Polymorphism
Alzheimer Disease
Genome
Cerebrospinal Fluid
Cell Size
Genes
Linear Models
Pathology

Keywords

  • ADNI
  • Amyloid-ß (Aß)
  • Cerebrospinal fluid (CSF)
  • GWIS
  • T-tau/Aß ratio
  • Total tau (T-tau)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Genome-wide association and interaction studies of CSF T-tau/Aβ42 ratio in ADNI cohort. / Li, Jin; Zhang, Qiushi; Chen, Feng; Meng, Xianglian; Liu, Wenjie; Chen, Dandan; Yan, Jingwen; Kim, Sungeun; Wang, Lei; Feng, Weixing; Saykin, Andrew; Liang, Hong; Shen, Li.

In: Neurobiology of Aging, Vol. 57, 01.09.2017, p. 247.e1-247.e8.

Research output: Contribution to journalArticle

Li, J, Zhang, Q, Chen, F, Meng, X, Liu, W, Chen, D, Yan, J, Kim, S, Wang, L, Feng, W, Saykin, A, Liang, H & Shen, L 2017, 'Genome-wide association and interaction studies of CSF T-tau/Aβ42 ratio in ADNI cohort', Neurobiology of Aging, vol. 57, pp. 247.e1-247.e8. https://doi.org/10.1016/j.neurobiolaging.2017.05.007
Li, Jin ; Zhang, Qiushi ; Chen, Feng ; Meng, Xianglian ; Liu, Wenjie ; Chen, Dandan ; Yan, Jingwen ; Kim, Sungeun ; Wang, Lei ; Feng, Weixing ; Saykin, Andrew ; Liang, Hong ; Shen, Li. / Genome-wide association and interaction studies of CSF T-tau/Aβ42 ratio in ADNI cohort. In: Neurobiology of Aging. 2017 ; Vol. 57. pp. 247.e1-247.e8.
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