Identification of genetic risk factors for brain amyloid deposition

After quality control, we retained 1,228 participants (52% female). Gene-based analyses identified a study-wide significant association for APOE (p-value = 1.82 × 10^-09), and eight additional genes with suggestive significance association (p-value<7.5 × 10^-04) including MPDZ, SEC16A, PLBD1, GLB1L2, KCNMB4, ELOVL5, SCART1 and SCN7A. According to the GTEx portal, five of these candidate genes are expressed in the brain. MPDZ encodes for a modular scaffold protein that was recently reported to be associated with Alzheimer's disease in African-Americans, supporting its involvement in amyloidosis risk (Ray et al., MedRxiv, 2023) CONCLUSION: We present the first time, a gene-based association study assessing the effect of potentially deleterious variants on amyloidosis. Importantly, we show that variants located in the APOE gene have a strong effect on this endophenotype. Interestingly, we point out additional candidate genes such as MPDZ that are potentially associated with amyloidosis. Additional replication, however, is required to validate our findings.