biostudies-literatureUnknown17Hu Z<h4>Introduction</h4>Previous studies have illuminated a significant genetic component in motor neuron disease (MND) pathogenesis, with several causative genes identified. However, a substantial proportion of MND cases remain genetically unexplained, particularly regarding the comprehensive contribution of rare, high-impact variants across the exome.<h4>Methods</h4>Leveraging whole-exome sequencing data from nearly half a million UK Biobank participants, we systematically investigated the association between high-confidence protein-truncating variants (HC PTVs) and MND risk in a Caucasian subset. Our large-scale gene-based association analysis utilized REGENIE software and LOFTEE-defined HC PTVs.<h4>Results</h4>We identified significant preliminary associations between HC PTVs in 14 genes Frontiers in aging neuroscience1735522https://www.ebi.ac.uk/biostudies/studies/S-EPMC12827591biostudies-literatureExploring rare coding variants in UK biobank: preliminary associations with motor neuron disease.PMC12827591Yan QQLiu JWan JJFan YHu ZfalseExploring rare coding variants in UK biobank: preliminary associations with motor neuron disease.<h4>Introduction</h4>Previous studies have illuminated a significant genetic component in motor neuron disease (MND) pathogenesis, with several causative genes identified. However, a substantial proportion of MND cases remain genetically unexplained, particularly regarding the comprehensive contribution of rare, high-impact variants across the exome.<h4>Methods</h4>Leveraging whole-exome sequencing data from nearly half a million UK Biobank participants, we systematically investigated the association between high-confidence protein-truncating variants (HC PTVs) and MND risk in a Caucasian subset. Our large-scale gene-based association analysis utilized REGENIE software and LOFTEE-defined HC PTVs.<h4>Results</h4>We identified significant preliminary associations between HC PTVs in 14 genes 2025-01-01T00:00:00Z20252026-06-06T03:22:55.043Z2026-06-06T03:10:51.331ZS-EPMC128275914158300410.3389/fnagi.2025.1735522