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

TitleAssociation of Alzheimer's disease GWAS loci with MRI markers of brain aging.
Publication TypeJournal Article
Year of Publication2015
AuthorsChauhan G, Adams HHH, Bis JC, Weinstein G, Yu L, Töglhofer AMaria, Smith A V, van der Lee SJ, Gottesman RF, Thomson R, Wang J, Yang Q, Niessen WJ, Lopez OL, Becker JT, Phan TG, Beare RJ, Arfanakis K, Fleischman D, Vernooij MW, Mazoyer B, Schmidt H, Srikanth V, Knopman DS, Jack CR, Amouyel P, Hofman A, DeCarli C, Tzourio C, van Duijn CM, Bennett DA, Schmidt R, Longstreth WT, Mosley TH, Fornage M, Launer LJ, Seshadri S, M Ikram A
Secondary AuthorsDebette S
JournalNeurobiol Aging
Volume36
Issue4
Pagination1765.e7-1765.e16
Date Published2015 Apr
ISSN1558-1497
KeywordsAging, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Female, Genome-Wide Association Study, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Organ Size, Polymorphism, Single Nucleotide, Risk, Sialic Acid Binding Ig-like Lectin 3
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). A weighted 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.

DOI10.1016/j.neurobiolaging.2014.12.028
Alternate JournalNeurobiol Aging
PubMed ID25670335
PubMed Central IDPMC4391343
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
R01HL7825 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
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R01 AG015928 / AG / NIA NIH HHS / United States
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