An APOE-independent cis-eSNP on chromosome 19q13.32 influences tau levels and late-onset Alzheimer's disease risk

NEUROBIOLOGY OF AGING

卷:66

Article

Rao, Shuquan¹  Ghani, Mahdi^2,3  Guo, Zhiyun¹  Deming, Yuetiva⁴  Wang, Kesheng⁵  Sims, Rebecca⁶  Mao, Canquan¹  Yao, Yao⁷  Cruchaga, Carlos^4,8  Stephan, Dietrich A.⁹  Rogaeva, Ekaterina^2,3 

[1] Southwest Jiaotong Univ, Sch Life Sci & Engn, 111,North 1st Sect,2nd Ring Rd, Chengdu 610031, Sichuan, Peoples R China

[2] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

[3] Univ Toronto, Dept Med, Toronto, ON, Canada

[4] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[5] East Tennessee State Univ, Coll Publ Hlth, Dept Biostat & Epidemiol, Johnson City, TN 37614 USA

[6] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Sch Med, Cardiff, Wales

[7] Chengdu Univ Tradit Chinese Med, Dept Fundamental Med, Chengdu, Sichuan, Peoples R China

[8] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA

[9] Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA USA

关键词: Late-onset Alzheimer's disease;    19q13.32;    APOE;    eQTL;    Tau level;   

DOI  :  10.1016/j.neurobiolaging.2017.12.027

来源: Elsevier

【 摘 要 】

Although multiple susceptibility loci for late-onset Alzheimer's disease (LOAD) have been identified, a large portion of the genetic risk for this disease remains unexplained. LOAD risk may be associated with single-nucleotide polymorphisms responsible for changes in gene expression (eSNPs). To detect eSNPs associated with LOAD, we integrated data from LOAD genome-wide association studies and expression quantitative trait loci using Sherlock (a Bayesian statistical method). We identified a cis-regulatory eSNP (rs2927438) located on chromosome 19q13.32, for which subsequent analyses confirmed the association with both LOAD risk and the expression level of several nearby genes. Importantly, rs2927438 may represent an APOE-independent LOAD eSNP according to the weak linkage disequilibrium of rs2927438 with the 2 polymorphisms (rs7412 and rs429358) defining the APOE-epsilon 2, -epsilon 3, and -epsilon 4 alleles. Furthermore, rs2927438 does not influence chromatin interaction events at the APOE locus or cis-regulation of APOE expression. Further exploratory analysis revealed that rs2927438 is significantly associated with tau levels in the cerebrospinal fluid. Our findings suggest that rs2927438 may confer APOE-independent risk for LOAD. (C) 2017 Elsevier Inc. All rights reserved.

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