In summary, we support previous studies, suggesting that (1) ABCA7 significantly influences AD risk; (2) ABCA7 p.G215S is likely to reduce the susceptibility to AD; (3) GWAS hits are pleomorphic loci harboring a complex spectrum of variants synergistically contributing to the disease phenotype with different mechanisms, effects (damaging, protective, and neutral), and effect sizes (0 < OR < 4); and (4) gene-based approaches are effective methods to mine genetic data and to accurately filter potential candidate genes. Here, ABCA7 is linked to Alzheimer disease.