Associations of targeted genetic variants with Alzheimer’s disease in African Americans and Nigerians

Abstract Background Genome‐wide association studies (GWAS) are often from populations with European ancestry (EA). To test whether the variants identified from recent GWAS are associated with age of onset for AD in an African Americans and Africans, we performed associations studies using data from the Indianapolis‐Ibadan Dementia Project (IIDP). Method In this longitudinal study of two community dwelling cohorts of elderly African Americans and Nigerians, 1108 African Americans and 1184 Nigerians who were dementia free at enrollment and had GWAS data were included in the analysis. During follow‐up, 104 African American individuals and 79 Nigerians developed AD. Mean follow up time was 8.8 years for both samples. Biomarkers for cardiovascular disease including lipids, homocysteine, C‐reactive protein were also measured at the time of GWAS sample collection. Cox’s proportional hazard models were used to determine the associations between previously reported genetic variants (n = 23) and the age of onset for AD, after adjusting for age, sex, education and the number APOE ε4 allele. For variants replicated in the African American and Nigerian samples, ANCOVA models were used to examine the association between the variants and blood biomarker levels. Result In the African American sample, one variant (rs3752246) in the adenosine triphosphate‐binding cassette subfamily A member 7 ( ABCA7 ) gene had a significant association with earlier AD onset (Hazard Ratio (HR) = 1.84, p = 0.0306). This ABCA7 variant was not observed in the Nigerian sample. In the Nigerian sample, one variant (rs9331949) in the clusterin gene ( CLU ) and another variant (rs10498663) in the solute carrier family 24 member 4 gene ( SLC24A4 ) were significantly associated with earlier onset of AD (rs9331949: HR = 2.05, p = 0.0069; rs10498663: HR = 1.55, p = 0.0401) while APOE was not significantly associated with age of onset for AD. In the Nigerian sample, rs10498663 in SLC24A4 was significantly associated with higher levels of triglycerides (p = 0.0012). Conclusion We replicated rs3752246 in ABCA7 for increased AD risk in African American participants in the IIDP study. In the Nigerian sample, the CLU and SLC24A4 variants were associated with increased AD risk and have stronger associations with AD than APOE . Further research is needed to explore biological pathways underlying these associations.