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Professor of Neurology and Neurogenetics, Utrecht University

As a research professional my aim is to understand the exact genetic contribution in every patient with ALS. I have a past performance with innovations both in the development of a custom reference panel that allowed the interrogation of rare genetic variation in a large sample of genotyped cases and controls (Van Rheenen et al., Nat Genet 2016), and the development of a tool that is near perfectly able to detect the C9orf72 repeat expansion in WGS data (Dolzhenko et al. Genome Res 2017). We have also just released an open access publication detailing the largest ALS GWAS as of 2021 (Van Rheenen et al., Nat Genet 2021, This shows specific genetic overlap but also differences between neurodegenerative diseases, a prime role for glutamatergic neurons in the initiation of ALS, opposed to a role for immune cells in other diseases like Alzheimer's disease and a causal role for cholesterol. We also show that GWAS hits in ALS can indicate various underlying genetic pathology (i.e. rare repeat expansions, rare single nucleotide variations, or independent common genetic variation in or near rare variant ALS genes).

I am leading a large-scale international collaboration (Project MinE, The project is in the process of whole-genome sequencing 15,000 ALS cases and 7,500 population-matched controls (with > 12,000 genomes completed by December 2017). This has already led to the identification of four new "ALS genes": TUBA4A, TBK1, C21orf2 and NEK1 (Kenna et al. Nat Genet 2016, Al-Chalabi et al. Nat Rev Neurology 2016). Upon completion, the project will have standardized phenotype information, whole- genome sequence data, SNP-array data, and methylation data for every sample.