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Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.
Friday,2015-08-28 11:58 America/Los_Angeles — zdrager
| Title | Association of Alzheimer's disease GWAS loci with MRI markers of brain aging. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Chauhan, G, Adams, HHH, Bis, JC, Weinstein, G, Yu, L, Töglhofer, AMaria, Smith, AVernon, 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, Ikram, AM, Debette, S |
| Journal | Neurobiol Aging |
| Volume | 36 |
| Issue | 4 |
| Pagination | 1765.e7-16 |
| Date Published | 2015 Apr |
| ISSN | 1558-1497 |
| Keywords | Aging, 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 | <p>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.</p> |
| DOI | 10.1016/j.neurobiolaging.2014.12.028 |
| Alternate Journal | Neurobiol. Aging |
| PubMed ID | 25670335 |
| PubMed Central ID | PMC4391343 |
| Grant List | AG033193 / AG / NIA NIH HHS / United States HHSN268200625226C / / PHS HHS / United States HHSN268200800007C / / PHS HHS / United States HHSN268201100005C / / PHS HHS / United States HHSN268201100006C / / PHS HHS / United States HHSN268201100007C / / PHS HHS / United States HHSN268201100008C / / PHS HHS / United States HHSN268201100009C / / PHS HHS / United States HHSN268201100010C / / PHS HHS / United States HHSN268201100011C / / PHS HHS / United States HHSN268201100012C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HL093029 / HL / NHLBI NIH HHS / United States N01-AG-12100 / AG / NIA NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01HC15103 / HC / NHLBI NIH HHS / United States N01HC55222 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States P20 MD006886 / MD / NIMHD NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States P30AG0101029 / AG / NIA NIH HHS / United States P30AG10161 / AG / NIA NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 AG040039 / AG / NIA NIH HHS / United States R01 AG040039 / AG / NIA NIH HHS / United States R01 AG08122 / AG / NIA NIH HHS / United States R01 NS17950 / NS / NINDS NIH HHS / United States R01AG15819 / AG / NIA NIH HHS / United States R01AG17917 / AG / NIA NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States R01HL103612 / HL / NHLBI NIH HHS / United States R01HL105756 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States R01HL7825 / HL / NHLBI NIH HHS / United States R21 NS076827 / NS / NINDS NIH HHS / United States RF1 AG015819 / AG / NIA NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States Z01 AG007270-08 / / Intramural NIH HHS / United States Z01 AG007380-02 / / Intramural NIH HHS / United States |