Jan Herman Veldink

NEK1 autophosphorylation is disrupted by amyotrophic lateral sclerosis-associated missense variants: activity biomarkers and structural insights

Kinase-dead controls, XIC quantification and phosphospecific antibodies establish pSer14, pThr156 and pSer418 as NEK1 autophosphorylation sites; a pThr156 assay shows ALS missense variants differ, with R261C reducing it most.

A Framework For Large-Scale Reconstruction Of Extended Pedigrees To Facilitate Gene Discovery In ALS

This paper develops a framework to reconstruct extended pedigrees for ALS patients with the C9orf72 repeat expansion, identifying novel familial relationships and shared genomic regions.

Excessive activation of the RAS/MAPK pathway triggers adult-onset motor axonal degeneration

This study identifies excessive RAS/MAPK pathway activation as a cause of adult-onset motor axonal degeneration in Drosophila, showing that inhibiting the pathway can rescue neurodegenerative phenotypes.

Whole-genome sequencing implicates rare, low-frequency and structural non-coding variation at the SCN5A locus in Brugada syndrome

This study identifies rare and low-frequency non-coding variants at the SCN5A locus associated with Brugada syndrome using whole-genome sequencing and functional assays.

Characterising the motif composition and allele length distribution of ZFHX3 GGC repeat expansions in amyotrophic lateral sclerosis

This study examines ZFHX3 GGC repeat expansions in ALS and finds no association with disease risk, but identifies diverse repeat motif compositions.

Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders

This study identifies digenic inheritance of SPG7 and AFG3L2 mutations as a cause of motor neuron and cerebellar disorders in 17 patients.

Trans-eQTLs reveal the architecture of human gene regulatory networks

The paper maps cis- and trans-eQTLs in blood samples to infer gene regulatory networks and prioritize trait-relevant pathways.

Comprehensive analysis across SMN2 excludes DNA methylation as an epigenetic biomarker for spinal muscular atrophy

This study analyzes SMN2 DNA methylation in SMA patients and finds no association with disease severity or treatment response, but identifies age-related methylation changes.

Towards a diagnostic test for sporadic ALS utilising deep learning and SNP microarrays

This paper develops a deep learning model using SNP microarray data to predict ALS risk with high accuracy across diverse populations and genotyping platforms.

The oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling, and therapeutic implications

The paper investigates oligogenic risk in ALS using genome sequencing data, finding that multiple rare variants in known ALS genes increase disease risk but not clinical outcomes.

Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis

The paper identifies sex-associated DNA methylation differences in ALS using a large-scale epigenome-wide association study and links them to survival outcomes.

Phenotype prediction using biologically interpretable neural networks on multi-cohort multi-omics data

The paper develops interpretable neural networks for multi-omics data to predict smoking status, age, and LDL levels, showing improved performance and generalizability across cohorts.

Sex-specific risk loci and modified MEF2C expression in ALS

The paper identifies sex-specific risk loci for ALS, including MEF2C, which is upregulated in female ALS motor neurons, and an X-chromosome locus at IL1RAPL2.

Computing Linkage Disequilibrium Aware Genome Embeddings using Autoencoders

The paper introduces a method to compress genetic data using autoencoders that leverage linkage disequilibrium structure, achieving high reconstruction accuracy while reducing data size.

Genetic and phenotype analyses of primary lateral sclerosis datasets from international cohorts

This study analyzes genetic and clinical data from PLS patients to assess the role of genetic testing and identify potential disease-associated variants.

Functional clustering of splice-altering variants in whole genome sequencing data reveals hidden heritability in rare variant disorder

SpliPath identifies pathogenic splice-altering variants in ALS by integrating SpliceAI predictions with transcriptomics data, revealing hidden heritability in rare variant disorders.

A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 as a significant cause of intellectual disability

The paper identifies a GCC repeat expansion in AFF3 as a significant cause of intellectual disability through a phenome-wide association study using DNA methylation profiling and UK Biobank data.

The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases

This study investigates the role of Neanderthal introgression and natural selection in the heritability of neurodegenerative diseases and finds no significant contribution from either.

Clinical testing panels for ALS: global distribution, consistency, and challenges

The paper evaluates the variability in ALS clinical genetic testing panels globally, finding inconsistent gene inclusion and potential diagnostic challenges.

OTTERS: A powerful TWAS framework leveraging summary-level reference data

OTTERS is a TWAS framework that uses summary-level eQTL reference data to estimate eQTL weights and perform omnibus TWAS, showing improved power and applicability.

Large-scale Analyses of CAV1 and CAV2 Suggest Their Expression is Higher in Post-mortem ALS Brain Tissue and Affects Survival

The paper analyzes CAV1 and CAV2 expression in ALS brain tissue and finds higher expression in ALS patients, associated with increased survival and slower disease progression.

Brain expression quantitative trait locus and network analysis reveals downstream effects and putative drivers for brain-related diseases

The paper integrates brain RNA-seq and genotype data to identify eQTLs and their downstream effects on brain-related diseases.

Molecular dynamics analysis of Superoxide Dismutase 1 mutations suggests decoupling between mechanisms underlying ALS onset and progression

This study uses molecular dynamics and clinical data to show structural and dynamic differences between WTL and MBR SOD1 variants, linking these to distinct ALS clinical outcomes.

Mutations in the tail domain of the neurofilament heavy chain gene increase the risk of amyotrophic lateral sclerosis

This study identifies NEFH tail domain mutations as risk factors for ALS through meta-analysis and variant burden analysis in case-control studies and whole-genome sequencing data.

Mitochondrial function determines severity but not risk of amyotrophic lateral sclerosis

The paper investigates how mitochondrial function affects ALS severity but not risk, identifying specific genetic and expression factors linked to disease progression.

C21orf2 mutations found in ALS disrupt primary cilia function

This study identifies C21orf2 mutations in ALS as causing cilia dysfunction and impaired sonic hedgehog signaling in motor neurons.

Genome-wide Identification of the Genetic Basis of Amyotrophic Lateral Sclerosis

This study identifies 690 candidate ALS genes using a hierarchical Bayesian model, highlighting genetic convergence on the distal axon and functional significance in motor neurons.

Unraveling the polygenic architecture of complex traits using blood eQTL meta-analysis

The paper uses blood eQTL meta-analysis to explore the polygenic architecture of complex traits, finding that trans-eQTLs are more informative for identifying causal genes than cis-eQTLs.

Loss of nucleoporin Nup50 is a risk factor for amyotrophic lateral sclerosis

The paper identifies NUP50 gene variants and reduced expression as risk factors for ALS through transcriptome-wide association and functional studies.

Non-Coding Genetic Analysis Implicates Interleukin 18 Receptor Accessory Protein 3'UTR in Amyotrophic Lateral Sclerosis

The paper identifies non-coding variants in the IL18RAP 3'UTR that reduce ALS risk by modulating neuro-inflammation through NF-κB signaling in microglia.