{"doi":"10.1002/mds.29144","title":"<scp>GRN</scp> Mutations Are Associated with Lewy Body Dementia","abstract":"BACKGROUND: Loss-of-function mutations in GRN are a cause of familial frontotemporal dementia, and common variants within the gene have been associated with an increased risk of developing Alzheimer's disease and Parkinson's disease. Although TDP-43-positive inclusions are characteristic of GRN-related neurodegeneration, Lewy body copathology has also been observed in many GRN mutation carriers. OBJECTIVE: The objective of this study was to assess a Lewy body dementia (LBD) case-control cohort for pathogenic variants in GRN and to test whether there is an enrichment of damaging mutations among patients with LBD. METHODS: We analyzed whole-genome sequencing data generated for 2591 European-ancestry LBD cases and 4032 neurologically healthy control subjects to identify disease-causing mutations in GRN. RESULTS: We identified six heterozygous exonic GRN mutations in seven study participants (cases: n = 6; control subjects: n = 1). Each variant was predicted to be pathogenic or likely pathogenic. We found significant enrichment of GRN loss-of-function mutations in patients with LBD compared with control subjects (Optimized Sequence Kernel Association Test P = 0.0162). Immunohistochemistry in three definite LBD cases demonstrated Lewy body pathology and TDP-43-positive neuronal inclusions. CONCLUSIONS: Our findings suggest that deleterious GRN mutations are a rare cause of familial LBD. © 2022 International Parkinson Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.","journal":"Movement Disorders","year":2022,"id":245160,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":238165,"name":"Shunsuke Koga","orcid":"0000-0001-8868-9700","position":1,"is_corresponding":false},{"id":290859,"name":"Zalak Shah","orcid":"0000-0002-7667-1025","position":2,"is_corresponding":false},{"id":240476,"name":"Ruth Chia","orcid":"0000-0002-4709-7423","position":3,"is_corresponding":false},{"id":65612,"name":"Rosa Rademakers","orcid":"0000-0002-4049-0863","position":4,"is_corresponding":false},{"id":241309,"name":"Clifton L. Dalgard","orcid":"0000-0003-2025-8239","position":5,"is_corresponding":false},{"id":108587,"name":"Bradley F. Boeve","orcid":"0000-0002-4153-8187","position":6,"is_corresponding":false},{"id":107088,"name":"Thomas G. Beach","orcid":"0000-0003-3296-6128","position":7,"is_corresponding":false},{"id":54753,"name":"Dennis W. Dickson","orcid":"0000-0001-7189-7917","position":8,"is_corresponding":false},{"id":17435,"name":"Owen A. Ross","orcid":"0000-0003-4813-756X","position":9,"is_corresponding":false},{"id":271284,"name":"Sonja W. Scholz","orcid":"0000-0002-6623-0429","position":10,"is_corresponding":false},{"id":880239,"name":"Paolo Reho","orcid":null,"position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T00:23:34.974895Z","pmid":"35810449","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}