Journal
NEUROBIOLOGY OF AGING
Volume 36, Issue 4, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.12.028
Keywords
Alzheimer; MRI-Markers; Genetic risk score; GWAS; Hippocampal volume
Categories
Funding
- NIA [N01-AG-12100]
- NEI
- NIDCD
- NHLBI
- NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, R01HL7825]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C, R01 AG040039, R21 NS076827, P20 MD006886]
- NIH Roadmap for Medical Research
- NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC15103, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393]
- National Institute of Neurological Disorders and Stroke (NINDS)
- Austrian Science Fond (FWF) [P20545-P05, P13180]
- Medical University of Graz
- Framingham Heart Study's National Heart, Lung, and Blood Institute [N01-HC-25195]
- Affymetrix, Inc for genotyping services [N02-HL-6-4278]
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center
- National Institute on Aging [R01 AG08122, AG033193, P30 AG0101029, P30AG10161, R01AG17917, R01AG15819]
- National Institute of Neurological Disorders and Stroke [R01 NS17950]
- Illinois Department of Public Health
- Netherlands Organization of Scientific Research NWO [175.010.2005.011]
- Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands Organization for Scientific Research (NWO)
- Netherlands Organization for the Health Research and Development (ZonMw) [916.13.054]
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- Internationale Stichting Alzheimer Onderzoek
- National Health and Medical Research Council (NHMRC) [403000, 491109, 606543]
- Wicking Dementia Education and Research Centre, Hobart
- NHMRC/National Heart Foundation Career Development Fellowship [606544]
- Fondation pour la Recherche Medicale
- Caisse Nationale Maladie des Travailleurs Salaries
- Direction Generale de la Sante
- Mutuelle Generale de l'Education Nationale (MGEN)
- Institut de la Longevite
- Conseils Regionaux of Aquitaine and Bourgogne
- Fondation de France
- Ministry of Research-INSERM Programme Cohortes et collections de donnees biologiques
- Eisai
- National Foundation for Alzheimer's Disease and Related Disorders
- Institut Pasteur de Lille
- Centre National de Genotypage
- Fondation Leducq
- Agence Nationale de la Recherche (Chaire d'Excellence)
- [UL1RR025005]
- [HL093029]
- Austrian Science Fund (FWF) [P13180] Funding Source: Austrian Science Fund (FWF)
Ask authors/readers for more resources
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. (C) 2015 Elsevier Inc. All rights reserved.
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