A large-scale, two-stage meta-analysis of genome-wide association studies (GWAS) was conducted to identify genetic risk factors for late-onset Alzheimer's disease (LOAD). In the first stage, data from four consortia (ADGC, CHARGE, EADI, and GERAD) were combined to perform a meta-analysis on 17,008 LOAD cases and 37,154 controls. In the second stage, 11,632 SNPs with moderate evidence of association in the first stage were genotyped in an independent set of 8,572 cases and 11,312 controls. The analysis identified 19 loci with genome-wide significance (P < 5 × 10−8), including 11 new susceptibility loci. These loci, which include *HLA-DRB5–HLA-DRB1*, *SORL1*, *PTK2B*, *SLC24A4-RIN3*, *DSG2*, *CD33*, *TREM2*, *INPP5D*, *MEF2C*, and *ZCWPW1*, provide new insights into the genetic architecture of LOAD. The study highlights the importance of pathways such as APP and tau in LOAD pathology and suggests the involvement of novel pathways, including hippocampal synaptic function, cytoskeletal function, and axonal transport. The findings also emphasize the need for further research to fully understand the role of these loci in the pathophysiology of Alzheimer's disease.A large-scale, two-stage meta-analysis of genome-wide association studies (GWAS) was conducted to identify genetic risk factors for late-onset Alzheimer's disease (LOAD). In the first stage, data from four consortia (ADGC, CHARGE, EADI, and GERAD) were combined to perform a meta-analysis on 17,008 LOAD cases and 37,154 controls. In the second stage, 11,632 SNPs with moderate evidence of association in the first stage were genotyped in an independent set of 8,572 cases and 11,312 controls. The analysis identified 19 loci with genome-wide significance (P < 5 × 10−8), including 11 new susceptibility loci. These loci, which include *HLA-DRB5–HLA-DRB1*, *SORL1*, *PTK2B*, *SLC24A4-RIN3*, *DSG2*, *CD33*, *TREM2*, *INPP5D*, *MEF2C*, and *ZCWPW1*, provide new insights into the genetic architecture of LOAD. The study highlights the importance of pathways such as APP and tau in LOAD pathology and suggests the involvement of novel pathways, including hippocampal synaptic function, cytoskeletal function, and axonal transport. The findings also emphasize the need for further research to fully understand the role of these loci in the pathophysiology of Alzheimer's disease.