The role of frontotemporal dementia associated genes in patients with Alzheimer's disease

• In this study, we systematically explore the relationship between FTD-associated genes and the risk of AD. • UBQLN1, MAPT, and HNRNPA1 interacted with proteins encoded by well-recognized AD-associated genes. Alzheimer's disease (AD) and frontotemporal dementia (FTD) overlap clinically and pathologically. However, the role of FTD-associated genes in patients with AD remained unclear. To explore the relationship between FTD-associated genes and AD risk, we investigated 14 FTD-associated genes via targeted next-generation sequencing panel or whole-genome sequencing in a total of 721 AD patients and 1391 controls. Common variant-based association analysis and gene-based association test of rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal (SKAT-O test) respectively. As a result, 2 common variants, UBQLN1 rs1044175 ( p value = 2.76 × 10 −4 ) and MAPT rs2258689 ( p value = 5.71 × 10 −4 ), differed significantly between AD patients and controls. Additionally, gene-based analysis aggregating rare variants demonstrated that HNRNPA1 reached statistical significance in the SKAT-O test ( p value = 2.24 × 10 −3 ). Protein–protein interaction analysis showed that UBQLN1, MAPT, and HNRNPA1 interacted with proteins encoded by well-recognized AD-associated genes. Our study indicated that UBQLN1, MAPT , and HNRNPA1 are implicated in the pathogenesis of AD in the mainland Chinese population.