Dataset Information

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

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.

SUBMITTER: Duan QQ

PROVIDER: S-EPMC10165003 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Duan Qing-Qing QQ Jiang Zheng Z Su Wei-Ming WM Gu Xiao-Jing XJ Wang Han H Cheng Yang-Fan YF Cao Bei B Gao Xia X Wang Yi Y Chen Yong-Ping YP

Frontiers in neuroscience 20230424

<h4>Background</h4>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.<h4>Method</h4>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.< ...[more]

PMID: 37168926

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Project description:ObjectiveAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the upper and lower motor neurons. Though the pathogenesis of ALS is still unclear, exploring the associations between risk factors and ALS can provide reliable evidence to find the pathogenesis. This meta-analysis aims to synthesize all related risk factors of ALS to understand this disease comprehensively.MethodsWe searched the following databases: PubMed, EMBASE, Cochrane library, Web of Science, and Scopus. Moreover, observational studies, including cohort studies, and case-control studies, were included in this meta-analysis.ResultsA total of 36 eligible observational studies were included, and 10 of them were cohort studies and the rest were case-control studies. We found six factors exacerbated the progression of disease: head trauma (OR = 1.26, 95% CI = 1.13, 1.40), physical activity (OR = 1.06, 95% CI = 1.04, 1.09), electric shock (OR = 2.72, 95% CI = 1.62, 4.56), military service (OR = 1.34, 95% CI = 1.11, 1.61), pesticides (OR = 1.96, 95% CI = 1.7, 2.26), and lead exposure (OR = 2.31, 95% CI = 1.44, 3.71). Of note, type 2 diabetes mellitus was a protective factor for ALS. However, cerebrovascular disease (OR = 0.99, 95% CI = 0.75, 1.29), agriculture (OR = 1.22, 95% CI = 0.74, 1.99), industry (OR = 1.24, 95% CI = 0.81, 1.91), service (OR = 0.47, 95% CI = 0.19, 1.17), smoking (OR = 1.25, 95% CI = 0.5, 3.09), chemicals (OR = 2.45, 95% CI = 0.89, 6.77), and heavy metal (OR = 1.5, 95% CI = 0.47, 4.84) were not risk factors for ALS based on meta-analyses.ConclusionsHead trauma, physical activity, electric shock, military service, pesticides, and lead were risk factors for ALS onset and progression. But DM was a protective factor. This finding provides a better understanding of ALS risk factors with strong evidence for clinicians to rationalize clinical intervention strategies.Inplsy registration numberhttps://inplasy.com/inplasy-2022-9-0118/, INPLASY202290118.

Project description:ImportanceHeritability describes the proportion of variance in the risk of developing a condition that is explained by genetic factors. Although amyotrophic lateral sclerosis (ALS) is known to have a complex genetic origin, disease heritability remains unclear.ObjectivesTo determine the extent of ALS heritability and assess the association of sex with disease transmission.Design, setting, and participantsA prospective population-based parent-offspring heritability study was conducted from January 1, 2008, to December 31, 2017 to assess ALS heritability, and was the first study to assess heritability in the context of known gene mutations of large effect. A total of 1123 incident cases of ALS, diagnosed according to the El Escorial criteria and recorded on the Irish ALS register, were identified. Ninety-two individuals were excluded (non-Irish parental origin [n = 86] and familial ALS [n = 6]), and 1117 patients were included in the final analysis.Main outcomes and measuresAnnual age-specific and sex-specific standardized ALS incidence and mortality-adjusted lifetime risk were determined. Sex-specific heritability estimates were calculated for the overall study cohort, for those known to carry the C9orf72 (OMIM 614260) variant, and for those with no known genetic risk.ResultsA total of 32 parent-child ALS dyads were identified during the study period. Affected offspring were younger at the onset of disease (mean age, 52.0 years; 95% CI, 48.8-55.3 years) compared with their parents (mean age, 69.6 years; 95% CI, 62.4-76.9 years; P = .008). Lifetime risk of developing ALS in first-degree relatives of individuals with ALS was increased compared with the general population (1.4% [32 of 2234] vs 0.3% [2.6 of 1000]; P < .001). Mean lifetime heritability of ALS for the overall study cohort was 52.3% (95% CI, 42.9%-61.7%) and 36.9% (95% CI, 19.8%-53.9%) for those with no known genetic risk. Heritability estimates were highest in mother-daughter pairings (66.2%; 95% CI, 58.5%-73.9%).Conclusions and relevanceThis population-based study confirms that up to 50% of variance in ALS has a genetic basis, and that the presence of the C9orf72 variant is an important determinant of heritability. First-degree relatives of individuals with ALS without a known genetic basis remain at increased risk of developing ALS compared with the general population. A higher heritability estimate in mother-daughter pairings points to a sex-mediated effect that has been previously unrecognized.

Dataset Information

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

Background

Method

Results

Conclusions

Systematic review registration

Publications

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

Similar Datasets

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