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

Jaeyoon Chung, Xulong Wang, Toru Maruyama, Yiyi Ma, Xiaoling Zhang, Jesse Mez, Richard Sherva, Haruko Takeyama, Kathryn L. Lunetta, Lindsay A. Farrer, Gyungah R. Jun

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    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 Aβ42 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 × 10-9) 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.

    Original languageEnglish
    JournalAlzheimer's and Dementia
    DOIs
    Publication statusAccepted/In press - 2018 Jan 1

    Fingerprint

    Endophenotypes
    Genome-Wide Association Study
    Alzheimer Disease
    Single Nucleotide Polymorphism
    Repression (Psychology)
    Biological Phenomena
    Brain
    Brain Diseases
    Neuroimaging
    Cerebrospinal Fluid
    Alleles

    Keywords

    • ADNI
    • Alzheimer's disease
    • Biomarker
    • Cerebrospinal fluid
    • Coexpression network
    • Endophenotypes
    • Genome-wide association
    • Logical memory
    • MRI
    • Tau

    ASJC Scopus subject areas

    • Epidemiology
    • Health Policy
    • Developmental Neuroscience
    • Clinical Neurology
    • Geriatrics and Gerontology
    • Cellular and Molecular Neuroscience
    • Psychiatry and Mental health

    Cite this

    Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages. / Chung, Jaeyoon; Wang, Xulong; Maruyama, Toru; Ma, Yiyi; Zhang, Xiaoling; Mez, Jesse; Sherva, Richard; Takeyama, Haruko; Lunetta, Kathryn L.; Farrer, Lindsay A.; Jun, Gyungah R.

    In: Alzheimer's and Dementia, 01.01.2018.

    Research output: Contribution to journalArticle

    Chung, J, Wang, X, Maruyama, T, Ma, Y, Zhang, X, Mez, J, Sherva, R, Takeyama, H, Lunetta, KL, Farrer, LA & Jun, GR 2018, 'Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages', Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2017.11.006
    Chung, Jaeyoon ; Wang, Xulong ; Maruyama, Toru ; Ma, Yiyi ; Zhang, Xiaoling ; Mez, Jesse ; Sherva, Richard ; Takeyama, Haruko ; Lunetta, Kathryn L. ; Farrer, Lindsay A. ; Jun, Gyungah R. / Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages. In: Alzheimer's and Dementia. 2018.
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