Evaluation of common and rare variants of Alzheimer's disease-causal genes in Parkinson's disease.

<bold>Introduction: </bold>Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative diseases in the elderly. Recently, some variants of AD-causal genes (APP, PSEN1, PSEN2) have been reported in PD. In this study, we investigated the association between coding variants of AD-causal genes and PD in a large Chinese population cohort.<bold>Methods: </bold>We performed whole-exome sequencing (WES) on 1,917 patients with early-onset or familial PD and 1,652 controls, and whole-genome sequencing (WGS) on 1,962 sporadic late-onset PD and 1,279 controls. Genetic and phenotypic data were analyzed with regression analyses and the optimized sequence kernel association test. Further validation study was performed by Fisher's exact test.<bold>Results: </bold>We found that rs75733498 in the PSEN2 gene was significantly associated with early-onset or familial PD; however, no significant relationship was discovered between rs75733498 and sporadic late-onset PD. The result of the validation study still revealed a significant association between rs75733498 and PD. We observed a suggestive association with APP gene in early-onset or familial PD when considering damaging missense variants alone (p = 0.018) or combined with loss-of-function variants (p = 0.029). Further phenotypic analysis did not demonstrate any significant associations.<bold>Conclusion: </bold>Our results support a possible genetic contribution of AD-causal genes to PD. These findings warrant further genetic and functional confirmation, and more powerful association studies will better decipher the mechanisms of PD. [ABSTRACT FROM AUTHOR]