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Genetic modification of the relationship between phosphorylated tau and neurodegeneration
Author(s) -
Hohman Timothy J.,
Koran Mary Ellen I.,
ThorntonWells Tricia A.
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.12.022
Subject(s) - single nucleotide polymorphism , genome wide association study , neurodegeneration , bonferroni correction , snp , neuroimaging , genetic association , disease , neuroscience , psychology , medicine , biology , genotype , genetics , gene , statistics , mathematics
Background A subset of individuals present at autopsy with the pathologic features of Alzheimer's disease having never manifest the clinical symptoms. We sought to identify genetic factors that modify the relationship between phosphorylated tau (PTau) and dilation of the lateral inferior ventricles. Methods We used data from 700 subjects enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). A genome‐wide association study approach was used to identify PTau × single nucleotide polymorphism (SNP) interactions. Variance explained by these interactions was quantified using hierarchical linear regression. Results Five SNP × PTau interactions passed a Bonferroni correction, one of which (rs4728029, POT1 , 2.6% of variance) was consistent across ADNI‐1 and ADNI‐2/GO subjects. This interaction also showed a trend‐level association with memory performance and levels of interleukin‐6 receptor. Conclusions Our results suggest that rs4728029 modifies the relationship between PTau and both ventricular dilation and cognition, perhaps through an altered neuroinflammatory response.