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.

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