Hypermethylation at CREBBP Is Associated with Cognitive Impairment in a Mexican American Cohort

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dc.creatorAbraham Daniel, Ann
dc.creatorSilzer, Talisa
dc.creatorSun, Jie
dc.creatorZhou, Zhengyang
dc.creatorHall, Courtney
dc.creatorPhillips, Nicole
dc.creatorBarber, Robert C.
dc.creator.orcid0000-0001-6857-0286 (Barber, Robert C.)
dc.creator.orcid0000-0002-9324-2687 (Phillips, Nicole R.)
dc.creator.orcid0000-0002-8039-418X (Zhou, Zhengyang)
dc.date.accessioned2023-06-07T18:15:35Z
dc.date.available2023-06-07T18:15:35Z
dc.date.issued2023-03-07
dc.description.abstractBACKGROUND: The aging Mexican American (MA) population is the fastest growing ethnic minority group in the US. MAs have a unique metabolic-related risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI), compared to non-Hispanic whites (NHW). This risk for cognitive impairment (CI) is multifactorial involving genetics, environmental, and lifestyle factors. Changes in environment and lifestyle can alter patterns and even possibly reverse derangement of DNA methylation (a form of epigenetic regulation). OBJECTIVE: We sought to identify ethnicity-specific DNA methylation profiles that may be associated with CI in MAs and NHWs. METHODS: DNA obtained from peripheral blood of 551 participants from the Texas Alzheimer's Research and Care Consortium was typed on the Illumina InfiniumĀ® MethylationEPIC chip array, which assesses over 850K CpG genomic sites. Within each ethnic group (N = 299 MAs, N = 252 NHWs), participants were stratified by cognitive status (control versus CI). Beta values, representing relative degree of methylation, were normalized using the Beta MIxture Quantile dilation method and assessed for differential methylation using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages in R. RESULTS: Two differentially methylated sites were significant: cg13135255 (MAs) and cg27002303 (NHWs) based on an FDR p < 0.05. Three suggestive sites obtained were cg01887506 (MAs) and cg10607142 and cg13529380 (NHWs). Most methylation sites were hypermethylated in CI compared to controls, except cg13529380 which was hypomethylated. CONCLUSION: The strongest association with CI was at cg13135255 (FDR-adjusted p = 0.029 in MAs), within the CREBBP gene. Moving forward, identifying additional ethnicity-specific methylation sites may be useful to discern CI risk in MAs.
dc.description.sponsorshipThis research project was supported (in part) by funding provided to the Texas Alzheimer's Research and Care Consortium by the Darrell K Royal Texas Alzheimer's Initiative, directed by the Texas Council on Alzheimer's Disease and Related Disorders. This work was also supported by the Office of Vice President for Research and Innovation, the Institute for Healthy Aging, and National Institutes of Health/National Institute on Aging (T32 AG020494) (2018 and 2020) including half predoctoral international fellowship through the Neurobiology of Aging and Alzheimer's Disease (NBAAD) Training Program 2021-2022 and R01AG070862 to RCB.
dc.identifier.citationAbraham Daniel, A., Silzer, T., Sun, J., Zhou, Z., Hall, C., Phillips, N., & Barber, R. (2023). Hypermethylation at CREBBP Is Associated with Cognitive Impairment in a Mexican American Cohort. Journal of Alzheimer's disease : JAD, 92(4), 1229-1239. https://doi.org/10.3233/JAD-221031
dc.identifier.issn1875-8908
dc.identifier.issue4
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32365
dc.identifier.volume92
dc.publisherIOS Press
dc.relation.urihttps://doi.org/10.3233/JAD-221031
dc.rights.holderĀ© 2023 The authors.
dc.rights.licenseAttribution-NonCommercial 4.0 International (CC BY-NC 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceJournal of Alzheimer's Disease
dc.subjectAlzheimer's disease
dc.subjectMexican Americans
dc.subjectepigenetics
dc.subjectmethylation
dc.subjectmild cognitive impairment
dc.subject.meshAged
dc.subject.meshHumans
dc.subject.meshCognitive Dysfunction / blood
dc.subject.meshCognitive Dysfunction / epidemiology
dc.subject.meshCognitive Dysfunction / ethnology
dc.subject.meshCognitive Dysfunction / genetics
dc.subject.meshCREB-Binding Protein / blood
dc.subject.meshCREB-Binding Protein / genetics
dc.subject.meshDNA Methylation / genetics
dc.subject.meshEpigenesis, Genetic / genetics
dc.subject.meshGenetic Predisposition to Disease / epidemiology
dc.subject.meshGenetic Predisposition to Disease / ethnology
dc.subject.meshGenetic Predisposition to Disease / genetics
dc.subject.meshMexican Americans / genetics
dc.subject.meshMinority Groups
dc.subject.meshRisk Factors
dc.subject.meshWhite / genetics
dc.titleHypermethylation at CREBBP Is Associated with Cognitive Impairment in a Mexican American Cohort
dc.typeArticle
dc.type.materialtext

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