Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.

TitleGenome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.
Publication TypeJournal Article
Year of Publication2018
AuthorsChung J, Wang X, Maruyama T, Ma Y, Zhang X, Mez J, Sherva R, Takeyama H, Lunetta KL, Farrer LA, Jun GR
Corporate AuthorsAlzheimer's Disease Neuroimaging Initiative
JournalAlzheimers Dement
Volume14
Issue5
Pagination623-633
Date Published2018 May
ISSN1552-5279
Abstract

INTRODUCTION: Genetic associations for endophenotypes of Alzheimer's disease (AD) in cognitive stages preceding AD have not been thoroughly evaluated.METHODS: We conducted genome-wide association studies for AD-related endophenotypes including hippocampal volume, logical memory scores, and cerebrospinal fluid Aβ and total/phosphorylated tau in cognitively normal (CN), mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative study.RESULTS: In CN subjects, study-wide significant (P < 8.3 × 10) loci were identified for total tau near SRRM4 and C14orf79 and for hippocampal volume near MTUS1. In mild cognitive impairment subjects, study-wide significant association was found with single nucleotide polymorphisms (SNPs) near ZNF804B for logical memory test of delayed recall scores. We found consistent expression patterns of C14orf40 and MTUS1 in carriers with risk alleles of expression SNPs and in brains of AD patients, compared with in the noncarriers and in brains of controls.DISCUSSION: Our findings for AD-related brain changes before AD provide insight about early AD-related biological processes.

DOI10.1016/j.jalz.2017.11.006
Alternate JournalAlzheimers Dement
PubMed ID29274321
PubMed Central IDPMC5938137
Grant ListU01 AG032984 / AG / NIA NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
K23 AG046377 / AG / NIA NIH HHS / United States
R01 AG048927 / AG / NIA NIH HHS / United States
RF1 AG057519 / AG / NIA NIH HHS / United States