CpG-related SNPs in the MS4A region have a dose-dependent effect on risk of late-onset Alzheimer disease
Autor: | Ma, Yiyi, Jun, Gyungah R, Chung, Jaeyoon, Zhang, Xiaoling, Kunkle, Brian W, Naj, Adam C, White, Charles C, Bennett, David A, De Jager, Philip L, Alzheimer’s Disease Genetics Consortium, Mayeux, Richard, Haines, Jonathan L, Pericak-Vance, Margaret A, Schellenberg, Gerard D, Farrer, Lindsay A, Lunetta, Kathryn L |
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Rok vydání: | 2019 |
Předmět: |
Risk
Male mQTL Aging Quantitative Trait Loci Neurodegenerative eQTL Alzheimer's Disease Medical and Health Sciences Cohort Studies Alzheimer Disease 80 and over Genetics Acquired Cognitive Impairment Humans 2.1 Biological and endogenous factors Genetic Predisposition to Disease Polymorphism Aetiology Aged DNA methylation epigenetics Alzheimer’s Disease Genetics Consortium Human Genome Neurosciences Brain Membrane Proteins Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Single Nucleotide Middle Aged Biological Sciences Prognosis Brain Disorders Neurological CpG Islands Female Dementia Dinucleoside Phosphates Genome-Wide Association Study Biotechnology Developmental Biology |
Zdroj: | Aging cell, vol 18, iss 4 |
Popis: | CpG-related single nucleotide polymorphisms (CGS) have the potential to perturb DNA methylation; however, their effects on Alzheimer disease (AD) risk have not been evaluated systematically. We conducted a genome-wide association study using a sliding-window approach to measure the combined effects of CGSes on AD risk in a discovery sample of 24 European ancestry cohorts (12,181 cases, 12,601 controls) from the Alzheimer's Disease Genetics Consortium (ADGC) and replication sample of seven European ancestry cohorts (7,554 cases, 27,382 controls) from the International Genomics of Alzheimer's Project (IGAP). The potential functional relevance of significant associations was evaluated by analysis of methylation and expression levels in brain tissue of the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP), and in whole blood of Framingham Heart Study participants (FHS). Genome-wide significant (p  |
Databáze: | OpenAIRE |
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