Systematic review of genetic association studies in people with Lewy body dementia

Sanghvi, Hazel; Singh, Ricky; Morrin, Hamilton; Rajkumar, Anto P.

Abstract

Objectives

Lewy body dementia (LBD) causes more morbidity, disability, and earlier mortality than Alzheimer disease. Molecular mechanisms underlying neurodegeneration in LBD are poorly understood. We aimed to do a systematic review of all genetic association studies that investigated people with LBD for improving our understanding of LBD molecular genetics and for facilitating discovery of novel biomarkers and therapeutic targets for LBD.

Methods

We systematically reviewed five online databases (PROSPERO protocol: CRD42018087114) and completed the quality assessment using the quality of genetic association studies tool.

Results

Eight thousand five hundred twenty?one articles were screened, and 75 articles were eligible to be included. Genetic associations of LBD with APOE, GBA, and SNCA variants have been replicated by two or more good quality studies. Our meta?analyses confirmed that APOE??4 is significantly associated with dementia with Lewy bodies (pooled odds ratio [POR] = 2.70; 95% CI, 2.37?3.07; P?

• Journal Article Type: Article
• Acceptance Date: Dec 21, 2019
• Online Publication Date: Jan 2, 2020
• Publication Date: 2020-05
• Deposit Date: Jan 7, 2020
• Publicly Available Date: Jan 3, 2021
• Journal: International Journal of Geriatric Psychiatry
• Print ISSN: 0885-6230
• Electronic ISSN: 1099-1166
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 35
• Issue: 5
• Pages: 436-448
• DOI: https://doi.org/10.1002/gps.5260
• Keywords: Geriatrics and Gerontology; Psychiatry and Mental health
• Public URL: https://nottingham-repository.worktribe.com/output/3682331
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1002/gps.5260
• Additional Information: This is the peer reviewed version of the following article: Sanghvi, H., Singh, R., Morrin, H. and Rajkumar, A.P. (2020), Systematic review of genetic association studies in people with Lewy body dementia. Int J Geriatr Psychiatry. Accepted Author Manuscript, which has been published in final form at https://doi.org/10.1002/gps.5260. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.