Abstract
Cerebral microbleeds are the presence of a group of pathological processes affecting the small arteries, arterioles, capillaries, and venules of the brain. Previous studies showed that cerebral microbleeds were associated with higher risk of dementia and stroke. We conducted a genome-wide association study of cerebral microbleeds to identify novel loci associated with the presence and progression of cerebral microbleeds. This study included 454 individuals composed by 176 subjects with cerebral microbleeds and 278 subjects without cerebral microbleeds in a non-Hispanic/Latino white population. Association of genetic variants with the presence and progression of cerebral microbleeds was assessed by logistic regression model. Potential genetic risk variants Apolipoprotein E (ApoE) polymorphisms were independently genotyped and checked the association with the presence and progression of cerebral microbleeds. No single-nucleotide polymorphisms (SNPs) associated with the presence or progression of cerebral microbleeds were identified at genome-wide significant level (P < 1 × 10−8). A total of 19 SNPs were associated with the presence of microbleeds at suggestive level (P < 1 × 10−5). One SNP was associated with lower progression risk for cerebral microbleeds with suggestive evidence (P < 1 × 10−5). ApoE ε4ε4 was independently associated with the presence and progression of cerebral microbleeds (odds ratio = 2.54, 95% confidence interval 1.08–6.00 and odds ratio = 5.1, 95% confidence interval 1.36–19.16). We highlighted 19 novel SNPs associated with the presence of cerebral microbleeds and one novel SNP associated with the progression of cerebral microbleeds for the first time. ApoE ε4ε4 was confirmed independently associated with the presence and progression of cerebral microbleeds.
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Acknowledgments
The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Funding
This study was supported by grants from the National Natural Science Foundation of China (81870915, 91849126); Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) and ZHANGJIANG LAB; Tianqiao and Chrissy Chen Institute; and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University. Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org).
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Li, HQ., Cai, WJ., Hou, XH. et al. Genome-Wide Association Study of Cerebral Microbleeds on MRI. Neurotox Res 37, 146–155 (2020). https://doi.org/10.1007/s12640-019-00073-3
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DOI: https://doi.org/10.1007/s12640-019-00073-3