{"doi":"10.1101/2020.09.23.20197558","title":"<i>LRRK2</i> p.M1646T is associated with glucocerebrosidase activity and with Parkinson’s disease","abstract":"Abstract Background and objectives The LRRK2 p.G2019S Parkinson’s disease (PD) variant is associated with elevated glucocerebrosidase (GCase) activity in peripheral blood. We aimed to evaluate the association of other LRRK2 variants with PD and its association with GCase activity. Methods LRRK2 and GBA were fully sequenced in 1,123 PD patients and 576 controls from the Columbia and PPMI cohorts, in which GCase activity was measured in dried blood spots by liquid chromatography-tandem mass spectrometry. Results LRRK2 p.M1646T was associated with increased GCase activity in the Columbia University cohort (β=1.58, p =0.0003), and increased but not significantly in the PPMI cohort (β=0.29, p= 0.58). p.M1646T was associated with PD (OR=1.18, 95%CI=1.09-1.28, p =7.33E-05) in 56,306 PD patients and proxy-cases, and 1.4 million controls. Conclusions Our results suggest that the p.M1646T variant is associated with risk of PD with a small effect and with increased GCase activity in peripheral blood.","journal":"medRxiv","year":2020,"id":124058,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":347907,"name":"Eric Yu","orcid":"0000-0003-3525-4564","position":1,"is_corresponding":false},{"id":279271,"name":"Lynne Krohn","orcid":"0000-0001-6554-1666","position":2,"is_corresponding":false},{"id":301064,"name":"Uladzislau Rudakou","orcid":"0000-0002-1411-7985","position":3,"is_corresponding":false},{"id":354247,"name":"Kheireddin Mufti","orcid":"0000-0002-0447-9624","position":4,"is_corresponding":false},{"id":301063,"name":"Jennifer A. Ruskey","orcid":"0000-0002-6392-5014","position":5,"is_corresponding":false},{"id":303111,"name":"Farnaz Asayesh","orcid":null,"position":6,"is_corresponding":false},{"id":346129,"name":"Sandra B. Laurent","orcid":null,"position":7,"is_corresponding":false},{"id":53270,"name":"Dan Spiegelman","orcid":"0000-0003-4971-8868","position":8,"is_corresponding":false},{"id":92182,"name":"Stanley Fahn","orcid":null,"position":9,"is_corresponding":false},{"id":347909,"name":"Cheryl Waters","orcid":"0000-0002-1908-8773","position":10,"is_corresponding":false},{"id":279483,"name":"S. Pablo Sardi","orcid":"0000-0001-9805-3677","position":11,"is_corresponding":false},{"id":230757,"name":"Sara Bandrés‐Ciga","orcid":"0000-0003-0056-1361","position":12,"is_corresponding":false},{"id":279481,"name":"Roy N. Alcalay","orcid":"0000-0002-5717-4875","position":13,"is_corresponding":false},{"id":263848,"name":"Ziv Gan‐Or","orcid":"0000-0003-0332-234X","position":14,"is_corresponding":false},{"id":297178,"name":"Konstantin Senkevich","orcid":"0000-0003-3407-5716","position":15,"is_corresponding":false},{"id":420604,"name":"Yuri L. Sosero","orcid":"0000-0002-9385-3920","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-18T23:15:07.789881Z","pmid":null,"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":[]}