Novel genetic profile linked to cognitive decline in Hispanics/Latinos

Abstract BACKGROUND The APOE ε4 allele has weaker association with ADRD outcomes in Hispanic/Latino populations compared to non‐Hispanic White and East Asian populations. METHODS We used whole‐genome sequencing data from 13,025 Hispanic/Latino adults to infer population groups (clusters) from short DNA sequences at the APOE gene region. We estimated the associations between these clusters and mild cognitive impairment (MCI) and age‐adjusted significant cognitive decline assessed via the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA) study ( n = 5334). We compared these associations to those of the conventional APOE alleles. RESULTS We identified three clusters of individuals. Relative to the largest Cluster 1, being in Cluster 3 had higher likelihood of having significant cognitive decline, with odds ratio (OR) = 1.47, 95% confidence interval (CI) [1.18, 1.84], p < 0.001. The association with having prevalent MCI at the SOL‐INCA exam was not statistically significant, with OR = 1.33, 95% CI [0.97, 1.83], p = 0.08. Associations of the ε4 allele with these traits were not statistically significant. DISCUSSION The new APOE profile has stronger risk association with age‐adjusted significant cognitive decline in SOL‐INCA Hispanics/Latinos compared to the ε4 allele.