ABCA7 rare variants and Alzheimer disease risk.

OBJECTIVE: To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting.

METHODS: We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls.

RESULTS: After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.68-7.35, p = 0.0002). Performing a meta-analysis with previously published data, we found that in a combined sample of 1,256 patients and 1,347 controls from France and Belgium, the OR was 2.81 (95% CI 1.89-4.20, p = 3.60 × 10(-7)).

CONCLUSIONS: These results confirm that ABCA7 LOF variants are enriched in patients with AD and extend this finding to predicted damaging missense variants.