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

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Systematic review of genetic association studies in people with Lewy body dementia. / Sanghvi, Hazel; Singh, Ricky; Morrin, Hamilton; Rajkumar, Anto P.

In: International Journal of Geriatric Psychiatry, Vol. 35, No. 5, 01.05.2020, p. 436-448.

Research output: Contribution to journalReview article

Harvard

Sanghvi, H, Singh, R, Morrin, H & Rajkumar, AP 2020, 'Systematic review of genetic association studies in people with Lewy body dementia', International Journal of Geriatric Psychiatry, vol. 35, no. 5, pp. 436-448. https://doi.org/10.1002/gps.5260

APA

Sanghvi, H., Singh, R., Morrin, H., & Rajkumar, A. P. (2020). Systematic review of genetic association studies in people with Lewy body dementia. International Journal of Geriatric Psychiatry, 35(5), 436-448. https://doi.org/10.1002/gps.5260

Vancouver

Sanghvi H, Singh R, Morrin H, Rajkumar AP. Systematic review of genetic association studies in people with Lewy body dementia. International Journal of Geriatric Psychiatry. 2020 May 1;35(5):436-448. https://doi.org/10.1002/gps.5260

Author

Sanghvi, Hazel ; Singh, Ricky ; Morrin, Hamilton ; Rajkumar, Anto P. / Systematic review of genetic association studies in people with Lewy body dementia. In: International Journal of Geriatric Psychiatry. 2020 ; Vol. 35, No. 5. pp. 436-448.

Bibtex Download

@article{eddc4887b75e4221998ef7d022c48e9a,
title = "Systematic review of genetic association studies in people with Lewy body dementia",
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-ε4 is significantly associated with dementia with Lewy bodies (pooled odds ratio [POR] = 2.70; 95{\%} CI, 2.37-3.07; P <.001) and Parkinson's disease dementia (POR = 1.60; 95{\%} CI, 1.21-2.11; P =.001). Other reported genetic associations that need further replication include variants in A2M, BCHE-K, BCL7C, CHRFAM7A, CNTN1, ESR1, GABRB3, MAPT, mitochondrial DNA (mtDNA) haplogroup H, NOS2A, PSEN1, SCARB2, TFAM, TREM2, and UCHL1. Conclusions: The reported genetic associations and their potential interactions indicate the importance of α-synuclein, amyloid, and tau pathology, autophagy lysosomal pathway, ubiquitin proteasome system, oxidative stress, and mitochondrial dysfunction in LBD. There is a need for larger genome-wide association study (GWAS) for identifying more LBD-associated genes. Future hypothesis-driven studies should aim to replicate reported genetic associations of LBD and to explore their functional implications.",
keywords = "apolipoprotein E, genetic association studies, genetics, Lewy body dementia, Parkinson disease",
author = "Hazel Sanghvi and Ricky Singh and Hamilton Morrin and Rajkumar, {Anto P.}",
year = "2020",
month = "5",
day = "1",
doi = "10.1002/gps.5260",
language = "English",
volume = "35",
pages = "436--448",
journal = "International Journal of Geriatric Psychiatry",
issn = "0885-6230",
number = "5",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Systematic review of genetic association studies in people with Lewy body dementia

AU - Sanghvi, Hazel

AU - Singh, Ricky

AU - Morrin, Hamilton

AU - Rajkumar, Anto P.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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-ε4 is significantly associated with dementia with Lewy bodies (pooled odds ratio [POR] = 2.70; 95% CI, 2.37-3.07; P <.001) and Parkinson's disease dementia (POR = 1.60; 95% CI, 1.21-2.11; P =.001). Other reported genetic associations that need further replication include variants in A2M, BCHE-K, BCL7C, CHRFAM7A, CNTN1, ESR1, GABRB3, MAPT, mitochondrial DNA (mtDNA) haplogroup H, NOS2A, PSEN1, SCARB2, TFAM, TREM2, and UCHL1. Conclusions: The reported genetic associations and their potential interactions indicate the importance of α-synuclein, amyloid, and tau pathology, autophagy lysosomal pathway, ubiquitin proteasome system, oxidative stress, and mitochondrial dysfunction in LBD. There is a need for larger genome-wide association study (GWAS) for identifying more LBD-associated genes. Future hypothesis-driven studies should aim to replicate reported genetic associations of LBD and to explore their functional implications.

AB - 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-ε4 is significantly associated with dementia with Lewy bodies (pooled odds ratio [POR] = 2.70; 95% CI, 2.37-3.07; P <.001) and Parkinson's disease dementia (POR = 1.60; 95% CI, 1.21-2.11; P =.001). Other reported genetic associations that need further replication include variants in A2M, BCHE-K, BCL7C, CHRFAM7A, CNTN1, ESR1, GABRB3, MAPT, mitochondrial DNA (mtDNA) haplogroup H, NOS2A, PSEN1, SCARB2, TFAM, TREM2, and UCHL1. Conclusions: The reported genetic associations and their potential interactions indicate the importance of α-synuclein, amyloid, and tau pathology, autophagy lysosomal pathway, ubiquitin proteasome system, oxidative stress, and mitochondrial dysfunction in LBD. There is a need for larger genome-wide association study (GWAS) for identifying more LBD-associated genes. Future hypothesis-driven studies should aim to replicate reported genetic associations of LBD and to explore their functional implications.

KW - apolipoprotein E

KW - genetic association studies

KW - genetics

KW - Lewy body dementia

KW - Parkinson disease

UR - http://www.scopus.com/inward/record.url?scp=85077976331&partnerID=8YFLogxK

U2 - 10.1002/gps.5260

DO - 10.1002/gps.5260

M3 - Review article

C2 - 31898332

AN - SCOPUS:85077976331

VL - 35

SP - 436

EP - 448

JO - International Journal of Geriatric Psychiatry

JF - International Journal of Geriatric Psychiatry

SN - 0885-6230

IS - 5

ER -

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