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Open AccessAuthor Correction: The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration
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Article
Open AccessUnsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data
Amyotrophic lateral sclerosis (ALS) displays considerable clinical and genetic heterogeneity. Machine learning approaches have previously been utilised for patient stratification in ALS as they can disentangle...
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Article
Open AccessCo-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells
HSP90 has emerged as an appealing anti-cancer target. However, HSP90 inhibitors (HSP90i) are characterized by limited clinical utility, primarily due to the resistance acquisition via heat shock response (HSR)...
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Article
Open AccessCalculating variant penetrance from family history of disease and average family size in population-scale data
Genetic penetrance is the probability of a phenotype when harbouring a particular pathogenic variant. Accurate penetrance estimates are important across biomedical fields including genetic counselling, disease...
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Article
Open AccessThe SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration
Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this internation...
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Article
Open AccessAuthor Correction: A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
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Article
Open AccessAmyotrophic lateral sclerosis and cerebellum
Amyotrophic lateral sclerosis (ALS) is a devastating, heterogeneous neurodegenerative neuromuscular disease that leads to a fatal outcome within 2–5 years, and yet, a precise nature of the association between ...
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Article
Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3′UTR protect against ALS
The noncoding genome is substantially larger than the protein-coding genome but has been largely unexplored by genetic association studies. Here, we performed region-based rare variant association analysis of ...
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Open AccessAuthor Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
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Article
Open AccessStructural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis
There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with o...
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Article
Open AccessCommon and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide a...
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Article
Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantita...
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Article
Open AccessA HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
There is increasing evidence that endogenous retroviruses (ERVs) play a significant role in central nervous system diseases, including amyotrophic lateral sclerosis (ALS). Studies of ALS have consistently iden...
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Open AccessMeta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders
People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm...
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Article
Open AccessFrequency and methylation status of selected retrotransposition competent L1 loci in amyotrophic lateral sclerosis
Long interspersed element-1 (LINE-1/L1) is the only autonomous transposable element in the human genome that currently mobilises in both germline and somatic tissues. Recent studies have identified correlation...
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Publisher Correction: Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein
To discover novel genes underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry-matched controls. We observed a significant excess of rare protein-truncating va...
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Article
Open AccessC9orf72 intermediate expansions of 24–30 repeats are associated with ALS
The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~ 40% familial cases and ~ 7% sporadic cases in the European population. In most people, the repe...
