ArticleAnnals of neurology2019
Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis.
Article in Annals of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 94 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
94 citing papers in PubMed, 5 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- A systematic review and functionalFrontiers in neuroscience · 2025Pooled it
- Physical activity as risk factor in amyotrophic lateral sclerosis: a systematic review and meta-analysis.Journal of neurology · 2023Pooled it
- Medications on hypertension, hyperlipidemia, diabetes, and risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022 · on this mapPooled it
- Pooled it
- Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology.Nature genetics · 2021Pooled it
- Associations of self-reported and objectively measured physical activity and amyotrophic lateral sclerosis risk.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Plasma Lipidome Is Dysregulated in Amyotrophic Lateral Sclerosis and Associated With Life-Course Adiposity Polygenic Risk.Journal of cachexia, sarcopenia and muscle · 2026Article
- Cholesterol in amyotrophic lateral sclerosis: a bystander, a biomarker, or a target?Atherosclerosis plus · 2026Review
- From Environment to Symptoms: Mapping Premorbid Risk Factors onto Clinical Features of ALS in a Patient-Reported Database in China.Neurology and therapy · 2026Article
- Genetic analysis of neurodegenerative diseases.The Journal of clinical investigation · 2026Review
- A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS.Communications biology · 2025Article
- Dietary lipid content modifies wah-1/AIFM1-associated phenotypes via LRK-1 and DRP-1 expression in C. elegans.Nature communications · 2025Article
- Shared burden of ultra-rare genetic variants across a spectrum of motor neuron diseases.Translational neurodegeneration · 2025Article
- Extreme exercise in males is linked to mTOR signalling and onset of amyotrophic lateral sclerosis.Brain : a journal of neurology · 2025Article
- Amyotrophic Lateral Sclerosis and Risk of Common Cancer: Mendelian Randomization Interrogation of Causality and Mediation.Phenomics (Cham, Switzerland) · 2025Article
- Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View.Metabolites · 2025Review
- Dysregulation of muscle cholesterol transport in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2025Article
- Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens.Human genomics · 2024Review
- A scoping review of statistical methods to investigate colocalization between genetic associations and microRNA expression in osteoarthritis.Osteoarthritis and cartilage open · 2024Article
- Circulating Levels of T-Cell Traits and the Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.Molecular neurobiology · 2024Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issuedCorrection.2020
Authors and funding
14 authors at 12 institutions in 6 countries.
Funding
Abstract
objectiveTo identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS).
methodsLinkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed.
resultsWe have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest.
interpretationHere, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470-481.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.