{"doi":"10.1101/2021.01.15.426824","title":"Association of a Common Genetic Variant with Parkinson’s Disease is Propagated through Microglia","abstract":"Abstract Studies of the genetic basis of Parkinson’s disease (PD) have identified many disease-associated genetic variants, but the mechanisms linking variants to pathogenicity are largely unknown. PD risk is attributed to both coding mutations in the Leucine-rich repeat kinase 2 ( LRRK2 ) gene and to common non-coding variation upstream of the LRRK2 locus. Here we show that the influence of genotype at non-coding variant rs76904798 on LRRK2 expression is propagated specifically through microglia, in contrast to evaluations based on general rather than genotype-dependent expression. We find evidence of microglia-specific regulatory regions that may modulate LRRK2 expression using single nuclei sequencing analyses of human frontal cortex and confirm these results in a human induced pluripotent stem cell-derived microglia model. Our study demonstrates that cell type is an important consideration in interrogation of the role of non-coding variation in disease pathogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214299,"datarank":0.5879634048306146,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.22827911391085887,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.22827911391085887,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":9,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":238912,"name":"Alexandra Beilina","orcid":null,"position":1,"is_corresponding":false},{"id":279276,"name":"Xylena Reed","orcid":"0000-0002-7563-9365","position":2,"is_corresponding":false},{"id":6986,"name":"Andrew Singleton","orcid":"0000-0001-5606-700X","position":3,"is_corresponding":false},{"id":252390,"name":"Cornelis Blauwendraat","orcid":"0000-0001-9358-8111","position":4,"is_corresponding":false},{"id":80301,"name":"J. Raphael Gibbs","orcid":"0000-0002-6985-0658","position":5,"is_corresponding":false},{"id":238914,"name":"Mark Cookson","orcid":null,"position":6,"is_corresponding":false},{"id":512135,"name":"Rebekah G. Langston","orcid":"0000-0003-0123-7934","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:46.604690Z","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":[]}