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

Pubmed ID: 25670335

Pubmed Central ID: PMC4391343

Journal: Neurobiology of aging

Publication Date: April 1, 2015

Affiliation: INSERM U897, University of Bordeaux, Bordeaux, France; University of Bordeaux, Bordeaux, FranceINSERM U897, University of Bordeaux, Bordeaux, France; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Neurology, Bordeaux University Hospital, Bordeaux, France. Electronic address: sdebette@bu.edu.

MeSH Terms: Humans, Male, Female, Alleles, Aging, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Magnetic Resonance Imaging, Risk, Organ Size, Apolipoproteins E, Alzheimer Disease, Brain, Hippocampus, Sialic Acid Binding Ig-like Lectin 3

Grants: N01-HC-25195, N01HC25195, HHSN268200800007C, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C, N01 HC015103, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01 AG015928, R01 AG020098, R01 AG023629, R01 HL080295, U01 HL080295, UL1 TR000124, U01HL080295, U01 HG004402, R01 HL059367, UL1RR025005, R01HL59367, UL1 RR025005, R01 HL086694, HHSN268200625226C, U01HG004402, R01HL087641, R01 HL087641, R01HL086694, P30 DK063491, R01 AG033193, U01 AG049505, R01 NS017950, RF1 AG015819, R01HL7825, Z01 AG007270-08, P30AG0101029, R01 NS17950, Z01 AG007380-02, P20 MD006886, R01 AG017917, AG033193, R01AG17917, R01 HL087652, HL093029, R01 HL093029, R01 HL105756, R01 AG008122, P30 AG010161, R21 NS076827, R01HL105756, R01 AG08122, P50 AG005133, R01AG15819, R01HL087652, P30AG10161, T32 HL007825, N01HC15103, P30 AG010129, R01 AG040039, R01HL103612, R01 AG015819, R01 HL103612, HHSN268201100009I, HHSN268201100005G, HHSN268201100008I, HHSN268201100011I, HHSN268201100005I, HHSN268201100007I, N01AG12100, R01 AG042292

Authors: Thomson R, Hofman A, Knopman DS, Amouyel P, Ikram MA, Launer LJ, Wang J, Longstreth WT, Gottesman RF, Mosley TH, Chauhan G, Bis JC, Weinstein G, Yu L, Töglhofer AM, Smith AV, van der Lee SJ, Yang Q, Niessen WJ, Lopez OL, Becker JT, Phan TG, Beare RJ, Arfanakis K, Fleischman D, Vernooij MW, Mazoyer B, Schmidt H, Srikanth V, Jack CR, DeCarli C, Tzourio C, van Duijn CM, Bennett DA, Schmidt R, Fornage M, Seshadri S, Debette S, Adams HHH

Cite As: Chauhan G, Adams HHH, Bis JC, Weinstein G, Yu L, Töglhofer AM, Smith AV, 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 Jr, Amouyel P, Hofman A, DeCarli C, Tzourio C, van Duijn CM, Bennett DA, Schmidt R, Longstreth WT Jr, Mosley TH, Fornage M, Launer LJ, Seshadri S, Ikram MA, Debette S. Association of Alzheimer's disease GWAS loci with MRI markers of brain aging. Neurobiol Aging 2015 Apr;36(4):1765.e7-1765.e16. Epub 2015 Jan 6.

Studies:

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.