Dataset Information

Association Between C-Reactive Protein and Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

ABSTRACT: Background: Until now, the relationship between C-reactive protein (CRP) levels and amyotrophic lateral sclerosis (ALS) risk has not been fully established. It is necessary to assess whether there is a causal relationship between C-reactive protein levels and ALS risk. Objective and Methods: We aimed to determine whether CRP has causal effects on risk of ALS. In this present study, summary-level data for ALS (20,806 cases and 59,804 controls) was obtained from large analyses of genome-wide association studies. For instrumental variables, 37 single nucleotide polymorphisms that had been previously identified to be related to CRP levels were used, including 4 SNPs of conservative CRP genetic variants and 33 SNPs of liberal CRP genetic variants. MR estimates were calculated using the inverse-variance weighted method, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. Results: There was no significant causal relationship between genetically predicted CRP levels and ALS risk (OR = 1.123, 95% CI = 0.963-1.309, p = 0.139) and results for the conservative CRP instruments were consistent (OR = 0.964, 95% CI = 0.830-1.119, p = 0.628). Pleiotropic bias was not observed in this study. Conclusions: This study suggests that genetically predicted CRP levels may not be a causal risk factor for ALS.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC9164009 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Association Between C-Reactive Protein and Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

Zhu Yahui Y Li Mao M Zhang Jinghong J Huang Xusheng X

Frontiers in genetics 20220520

<b>Background:</b> Until now, the relationship between C-reactive protein (CRP) levels and amyotrophic lateral sclerosis (ALS) risk has not been fully established. It is necessary to assess whether there is a causal relationship between C-reactive protein levels and ALS risk. <b>Objective and Methods:</b> We aimed to determine whether CRP has causal effects on risk of ALS. In this present study, summary-level data for ALS (20,806 cases and 59,804 controls) was obtained from large analyses of gen ...[more]

PMID: 35669191

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Project description:Amyotrophic lateral sclerosis is a relatively common and rapidly progressive neurodegenerative disease that, in the majority of cases, is thought to be determined by a complex gene-environment interaction. Exponential growth in the number of performed genome-wide association studies combined with the advent of Mendelian randomization is opening significant new opportunities to identify environmental exposures that increase or decrease the risk of amyotrophic lateral sclerosis. Each of these discoveries has the potential to shape new therapeutic interventions. However, to do so, rigorous methodological standards must be applied in the performance of Mendelian randomization. We have reviewed Mendelian randomization studies performed in amyotrophic lateral sclerosis to date. We identified 20 Mendelian randomization studies, including evaluation of physical exercise, adiposity, cognitive performance, immune function, blood lipids, sleep behaviours, educational attainment, alcohol consumption, smoking and type 2 diabetes mellitus. We have evaluated each study using gold standard methodology supported by the Mendelian randomization literature and the STROBE-Mendelian randomization checklist. Where discrepancies exist between Mendelian randomization studies, we suggest the underlying reasons. A number of studies conclude that there is a causal link between blood lipids and risk of amyotrophic lateral sclerosis; replication across different datasets and even different populations adds confidence. For other putative risk factors, such as smoking and immune function, Mendelian randomization studies have provided cause for doubt. We highlight the use of positive control analyses in choosing exposure single nucleotide polymorphisms (SNPs) to make up the Mendelian randomization instrument, use of SNP clumping to avoid false positive results due to SNPs in linkage and the importance of multiple testing correction. We discuss the implications of survival bias for study of late age of onset diseases such as amyotrophic lateral sclerosis and make recommendations to mitigate this potentially important confounder. For Mendelian randomization to be useful to the amyotrophic lateral sclerosis field, high methodological standards must be applied to ensure reproducibility. Mendelian randomization is already an impactful tool, but poor-quality studies will lead to incorrect interpretations by a field that includes non-statisticians, wasted resources and missed opportunities.

Dataset Information

Association Between C-Reactive Protein and Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

Publications

Association Between C-Reactive Protein and Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

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