Risk factors of amyotrophic lateral sclerosis: a global meta-summary

Qing-Qing Duan; Zheng Jiang; Wei-Ming Su; Xiao-Jing Gu; Han Wang; Yang-Fan Cheng; Bei Cao; Xia Gao; Yi Wang; Yong-Ping Chen

doi:10.3389/fnins.2023.1177431

Risk factors of amyotrophic lateral sclerosis: a global meta-summary

Front Neurosci. 2023 Apr 24:17:1177431. doi: 10.3389/fnins.2023.1177431. eCollection 2023.

Authors

Qing-Qing Duan^{1

2

3}, Zheng Jiang^{1

2

3}, Wei-Ming Su^{1

2

3}, Xiao-Jing Gu⁴, Han Wang⁵, Yang-Fan Cheng^{1

2

3}, Bei Cao^{1

2

3}, Xia Gao⁶, Yi Wang⁵, Yong-Ping Chen^{1

2

3}

Affiliations

¹ Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Lab of Neurodegenerative Disorders, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
³ Centre for Rare Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁴ Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁵ Department of Pathophysiology, West China College of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
⁶ Department of Geriatrics, Dazhou Central Hospital, Dazhou, Sichuan, China.

Abstract

Background: The etiology of amyotrophic lateral sclerosis (ALS) remains largely unknown. This study aimed to summarize the relationship between ALS and its genetic and non-genetic risk factors.

Method: A search of relevant literature from PubMed, Embase, and Cochrane Database from inception to December 2022 was performed. Random-effects or fixed-effects models were performed by Stata MP 15.0 to pool multivariate or adjusted ratios (OR). PROSPERO registration number: CRD42022301549.

Results: 230 eligible studies were included, of which 67 involved 22 non-genetic factors, and 163 involved genetic factors. Four aspects of non-genetic factors, including lifestyle, environmental and occupational exposures, pre-existing diseases/comorbidity and medical exposures, and others, were analyzed. Exposure to heavy metals (OR = 1.79), pesticides (OR = 1.46), solvents (OR = 1.37), previous head trauma (OR = 1.37), military service (OR = 1.29), stroke (OR = 1.26), magnetic field (OR = 1.22) and hypertension (OR = 1.04) are significant risk factors, but use of antidiabetics (OR = 0.52), high BMI (OR = 0.60 for obese and overweight vs. normal and underweight), living in urban (OR = 0.70), diabetes mellitus (OR = 0.83), and kidney disease (OR = 0.84) decrease the risk for ALS. In addition, eight common ALS-related genes were evaluated, the mutation frequencies of these genes were ranked from highest to lowest as SOD1 (2.2%), C9orf72 (2.1%), ATXN2 (1.7%), FUS (1.7%), TARDBP (0.8%), VCP (0.6%), UBQLN2(0.6%) and SQSTM1 (0.6%) in all the ALS patients.

Conclusions: Our findings suggested that effective intervention for risk exposure and timely modification of lifestyle might prevent the occurrence of ALS. Genetic mutations are important risk factors for ALS and it is essential to detect genetic mutations correctly and scientifically.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=301549, identifier: CRD42022301549.

Keywords: amyotrophic lateral sclerosis (ALS); etiology; genes; odds ratio; onset; risk.

Publication types

Systematic Review

Grants and funding

This study was supported by the National Key Research and Development Program of China (Grant No. 2022YFC2703101 to Y-PC), the National Natural Science Fund of Sichuan (Grant No. 2022NSFSC0749 to BC), the Science and Technology Bureau Fund of Sichuan Province (No. 2021YFS0051 to YW and No. 2023YFS0269 to Y-PC), and the National Natural Science Fund of China (Grant No. 81971188 to Y-PC).