A polygenic risk score for Alzheimer’s disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.
Year: 2023
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. METHODS: We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. RESULTS: A simple sum of 5 PRSs ("PRSsum"), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-[Formula: see text] and APOE-[Formula: see text] alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-[Formula: see text] and APOE-[Formula: see text] alleles were not associated with MCI. DISCUSSION: A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-[Formula: see text] and APOE-[Formula: see text] alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults.
Source: Alzheimer s Research & Therapy
Institutions: Brigham and Women's Hospital, Harvard University, Wayne State University, University of California, San Francisco, University of California San Diego, Albert Einstein College of Medicine, University of Illinois Chicago, Rush University Medical Center, University of North Carolina at Chapel Hill, University of California, Davis, The University of Texas Health Science Center at Houston
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,690
Funders: Office of Dietary Supplements, University of Miami, Northwestern University, San Diego State University, University of Washington, National Institutes of Health, University of Illinois at Urbana-Champaign, Gillings School of Public Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Institute on Minority Health and Health Disparities
Awards: G1081972346, G1121130830, G122677224, G1312369436, G1327559120, G1349668216, Hispanic Community Health Study, G1455175283, Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA), MRI Measures of Cerebrovascular Injury and AD Atrophy in a Study of Latinos, G1818487580, G1866572497, G1888983140, G1984718218, G2128161193, G2466919156, HISPANIC COMMUNITY HEALTH STUDY - FIELD CENTER, G2644289446, G2645088300, G2651066328, G2655143993, Using Genetic and Blood Metabolites to Understand the Risk of Alzheimer's Disease in Latinos, G2866617920, Hispanic Community Health Study, G3614733703, G3667269547, G3722034730, Study of Latinos Investigation of Neurocognitive Aging 2, G432753757, Hispanic Community Health Study, G4421869008, G4441691082, G4592244384, San Diego Leading the Advancement of Underrepresented Neuroscientists for Change (LAUNCH) Program, G5015503974, G5102588038, G5129651400, G5223154479, G528357465, G5397198720, HISPANIC COMMUNITY HEALTH STUDY - COORDINATING CENTER, G543802643, G5785169696, G5935820280, G596642789, G5993399974, G6088185517, G6149955053, G6202424770, Neurocognitive aging, MCI and Alzheimer's disease DNA methylation among diverse Latinos, G6914194341, G7132511053, Exploring Sleep in Neurocognitive Aging and Alzheimer's Research (eSANAR), G820454163, G8932431361, G8987601928, G9000199330, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Study of Latinos-Investigation of Neurocognitive Aging-Alzheimer's disease, UC Davis Alzheimer's Disease Research Center, San Diego Alzheimer's Disease Resource Center for Minority Aging Research (San Diego AD-RCMAR), Novel imaging genetic biomarkers for sporadic frontotemporal dementia through machine learning, G937084196
OpenAlex ID: W4386287129