{"doi":"10.1101/2020.06.26.174276","title":"Genome-Wide Association Study Meta-Analysis for Parkinson’s Disease Motor Subtypes","abstract":"Abstract OBJECTIVE To discover genetic determinants of Parkinson disease (PD) motor subtypes, including Tremor Dominant (TD) and Postural Instability/Gait Difficulty (PIGD) forms. METHODS In 3,212 PD cases of European ancestry, we performed a genome-wide association study (GWAS) examining two complementary outcome traits derived from the Unified Parkinson’s Disease Rating Scale (UPDRS), including dichotomous motor subtype (TD vs. PIGD) or a continuous tremor / PIGD score ratio. Logistic or linear regression models were adjusted for sex, age of onset, disease duration, and 5 ancestry principal components, followed by meta-analysis. RESULTS Among 71 established PD risk variants, we detected multiple suggestive associations with PD motor subtype, including GPNMB ( rs199347 , p subtype = 0.01, p ratio = 0.03), SH3GL2 ( rs10756907 , p subtype = 0.02, p ratio = 0.01), HIP1R ( rs10847864 , p subtype = 0.02), RIT2 ( rs12456492 , p subtype = 0.02), and FBRSL1 ( rs11610045 , p subtype = 0.02). A PD genetic risk score integrating all 71 PD risk variants was also associated with subtype ratio (p = 0.026, ß = −0.04, 95% CI = −0.07, 0). Based on top results of our GWAS, we identify a novel suggestive association at the STK32B locus (rs2301857, p ratio = 6.6×10 −7 ), which harbors an independent risk allele for essential tremor. CONCLUSIONS Multiple PD risk alleles may also modify clinical manifestations to influence PD motor subtype. The discovery of a novel variant at STK32B suggests a possible overlap between genetic risk for essential tremor and tremor-dominant PD.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130207,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7764,"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":234498,"name":"Rami Al‐Ouran","orcid":null,"position":1,"is_corresponding":false},{"id":575748,"name":"Rainer von Coelln","orcid":"0000-0001-7651-2780","position":2,"is_corresponding":false},{"id":252390,"name":"Cornelis Blauwendraat","orcid":"0000-0001-9358-8111","position":3,"is_corresponding":false},{"id":575746,"name":"Emily J. Hill","orcid":"0000-0002-5267-570X","position":4,"is_corresponding":false},{"id":582496,"name":"Lan Luo","orcid":"0000-0002-1314-4367","position":5,"is_corresponding":false},{"id":576530,"name":"Amanda Stillwell","orcid":null,"position":6,"is_corresponding":false},{"id":582497,"name":"Emily Young","orcid":"0000-0002-1511-8533","position":7,"is_corresponding":false},{"id":45805,"name":"Manuela Tan","orcid":"0000-0001-5835-669X","position":8,"is_corresponding":false},{"id":582498,"name":"Calwing Liao","orcid":"0000-0001-6169-7137","position":9,"is_corresponding":false},{"id":271544,"name":"Dena Hernández","orcid":"0000-0002-0188-9927","position":10,"is_corresponding":false},{"id":271545,"name":"Lasse Pihlstrøm","orcid":"0000-0002-7635-8645","position":11,"is_corresponding":false},{"id":45817,"name":"Donald G. Grosset","orcid":"0000-0002-2757-8203","position":12,"is_corresponding":false},{"id":582499,"name":"Lisa Shulman","orcid":"0000-0001-9832-1897","position":13,"is_corresponding":false},{"id":110460,"name":"Zhandong Liu","orcid":"0000-0002-7608-0831","position":14,"is_corresponding":false},{"id":53271,"name":"Guy A. Rouleau","orcid":"0000-0001-8403-1418","position":15,"is_corresponding":false},{"id":130825,"name":"Mike A. Nalls","orcid":null,"position":16,"is_corresponding":false},{"id":6986,"name":"Andrew Singleton","orcid":"0000-0001-5606-700X","position":17,"is_corresponding":false},{"id":45815,"name":"Huw R. Morris","orcid":"0000-0002-5473-3774","position":18,"is_corresponding":false},{"id":92189,"name":"Joseph Jankovic","orcid":"0000-0003-4129-3674","position":19,"is_corresponding":false},{"id":40753,"name":"Joshua Shulman","orcid":"0000-0001-6382-5841","position":20,"is_corresponding":false},{"id":575747,"name":"Isabel Alfradique‐Dunham","orcid":"0000-0002-7723-2956","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T23:15:53.196774Z","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":[]}