Association of Alzheimer's disease GWAS loci with MRI markers of brain aging

Ganesh Chauhan, Hieab H.H. Adams, Joshua C. Bis, Galit Weinstein, Lei Yu, Anna Maria Töglhofer, Albert Vernon Smith, Sven J. van der Lee, Rebecca F. Gottesman, Wiro J. Niessen, More Authors

    Research output: Contribution to journalArticleScientificpeer-review

    48 Citations (Scopus)

    Abstract

    Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N= 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (. p= 0.0054) and CD33 (rs3865444) with smaller intracranial volume (. p= 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (. p= 0.0006) and BIN1 with HV (. p= 0.00089). Aweighted AD genetic risk score was associated with smaller HV (beta ± SE=-0.047 ± 0.013, p= 0.00041), even after excluding the APOE locus (. p= 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.

    Original languageEnglish
    Pages (from-to)1765.e7-1765.e16
    JournalNeurobiology of Aging
    Volume36
    Issue number4
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Alzheimer
    • Genetic risk score
    • GWAS
    • Hippocampal volume
    • MRI-Markers

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