No clear evidence for relationships of apolipoprotein E genotype with measures of common infections in three UK cohorts

Abstract APOE genotype is a very strong genetic risk factor for late-onset Alzheimer’s disease (AD). This relationship may involve mediation by common infections—several of which are also dementia risk factors. We investigated associations of APOE ε2 and ε4 carriage with serostatus and antibody titres to 14 common pathogens in three population-based cohorts (UK Biobank, National Survey of Health and Development, Southall and Brent Revisited). We conducted analyses in each cohort using mixed models, including age, sex and genetic principal components as fixed effects, and genetic relatedness as a random effect. In secondary analyses, we additionally assessed (i) relationships of APOE ε2 and ε4 dosage (i.e. number of copies of the allele of interest), and (ii) relationships of APOE genotype with continuous antibody titres (rank-based inverse normal transformed). Findings were meta-analysed across cohorts (n = 10,059) using random-effects models and corrected for multiple tests using the false discovery rate. We found no clear evidence of relationships between APOE genotype and serostatus or antibody titres to any pathogen, with no associations observed in any of our analyses following multiple testing correction. These findings do not support roles for various common infections found in the UK as mediators of APOE effects on AD risk.