Genetic Relationship between Alzheimer's Disease and Schizophrenia. (20th December 2022)

• Record Type: Journal Article
• Authors: Chen, Jingchun; Lu, Yimei; Cue, Joan Manuel; Patel, Neel; Zheng, Jennifer J.; Cummings, Melika J.; Do, Jenifer
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.065861
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Large genome‐wide association studies (GWASs) have demonstrated that common genetic variation contributes to the heritability of brain disorders, including Alzheimer's disease and schizophrenia. Patients with Alzheimer's disease and schizophrenia often have similar symptoms such as cognitive decline and hallucinations. Excessive synaptic pruning resulting from neuroinflammation and microglial activation are considered to play an important role in the development of both diseases. However, the genetic correlation between Alzheimer's disease and schizophrenia is unclear. Method: In this study, we used genotyping data of Alzheimer's disease and schizophrenia to examine the genetic relationship between the two diseases. We calculated polygenic risk scores (PRSs) at multiple thresholds for both diseases and tested their relationship using logistic and linear regression. Result: We found that schizophrenia PRSs were negatively associated with Alzheimer's disease at multiple thresholds. The most significant association (p = 2.24 x 10 ‐9 ) was obtained at GWAS threshold p = 0.5. Vice versa, Alzheimer's disease PRSs were positively associated with schizophrenia. The most significant signal (p = 4.10 x 10 ‐8 ) was obtained at GWAS threshold p = 0.1. Logic regression showed there was a strong correlation between the best schizophrenia PRSs and diagnosis of Alzheimer's disease. The same held with the best Alzheimer's disease PRSs and diagnosis of schizophrenia. Further, we found that there was a significant linear correction between the best PRSs of Alzheimer's disease and schizophrenia in the Alzheimer's disease dataset (R = 0.27, p < 2.2 x 10 ‐16 ). Conclusion: Our study indicated that there is a strong genetic correlation between Alzheimer's disease and schizophrenia, suggesting GWAS data from each disease might help to build a better risk prediction model for clinical risk assessment. Further studies on the shared risk variants/genes/pathways may help to better understand the mechanisms behind the two diseases for earlier disease prediction, diagnosis, and prevention.