{"doi":"10.1093/braincomms/fcae146","title":"Genome-wide meta-analysis of short-tandem repeats for Parkinson’s disease risk using genotype imputation","abstract":"Abstract Idiopathic Parkinson’s disease is determined by a combination of genetic and environmental factors. Recently, the first genome-wide association study on short-tandem repeats in Parkinson’s disease reported on eight suggestive short-tandem repeat-based risk loci (α = 5.3 × 10−6), of which four were novel, i.e. they had not been implicated in Parkinson’s disease risk by genome-wide association analyses of single-nucleotide polymorphisms before. Here, we tested these eight candidate short-tandem repeats in a large, independent Parkinson’s disease case–control dataset (n = 4757). Furthermore, we combined the results from both studies by meta-analysis resulting in the largest Parkinson’s disease genome-wide association study of short-tandem repeats to date (n = 43 844). Lastly, we investigated whether leading short-tandem repeat risk variants exert functional effects on gene expression regulation based on methylation quantitative trait locus data in human ‘post-mortem’ brain (n = 142). None of the eight previously reported short-tandem repeats were significantly associated with Parkinson’s disease in our independent dataset after multiple testing correction (α = 6.25 × 10−3). However, we observed modest support for short-tandem repeats near CCAR2 and NCOR1 in the updated meta-analyses of all available data. While the genome-wide meta-analysis did not reveal additional study-wide significant (α = 6.3 × 10−7) short-tandem repeat signals, we identified seven novel suggestive Parkinson’s disease short-tandem repeat risk loci (α = 5.3 × 10−6). Of these, especially a short-tandem repeat near MEIOSIN showed consistent evidence for association across datasets. CCAR2, NCOR1 and one novel suggestive locus identified here (LINC01012) emerged from colocalization analyses showing evidence for a shared causal short-tandem repeat variant affecting both Parkinson’s disease risk and cis DNA methylation in brain. Larger studies, ideally using short-tandem repeats called from whole-sequencing data, are needed to more fully investigate their role in Parkinson’s disease.","journal":"Brain Communications","year":2024,"id":444535,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9417,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316706,"name":"Kimberly C. Paul","orcid":"0000-0002-4476-2352","position":1,"is_corresponding":false},{"id":440339,"name":"Susan Searles Nielsen","orcid":"0000-0001-7768-4736","position":2,"is_corresponding":false},{"id":1260426,"name":"David Gmelin","orcid":null,"position":3,"is_corresponding":false},{"id":7732,"name":"Valerija Dobričić","orcid":"0000-0001-8559-1097","position":4,"is_corresponding":false},{"id":1260026,"name":"Vivian Altmann","orcid":"0000-0002-7320-2012","position":5,"is_corresponding":false},{"id":936109,"name":"Marcel Schilling","orcid":"0000-0002-3453-7792","position":6,"is_corresponding":false},{"id":338794,"name":"Jeff M. Bronstein","orcid":"0000-0002-2961-8918","position":7,"is_corresponding":false},{"id":1151,"name":"André Franke","orcid":"0000-0003-1530-5811","position":8,"is_corresponding":false},{"id":28444,"name":"Michael Wittig","orcid":"0000-0003-1103-4196","position":9,"is_corresponding":false},{"id":461712,"name":"Laura Parkkinen","orcid":"0000-0002-3392-8564","position":10,"is_corresponding":false},{"id":402169,"name":"Johnni Hansen","orcid":"0000-0002-9342-2725","position":11,"is_corresponding":false},{"id":17538,"name":"Harvey Checkoway","orcid":"0000-0001-7119-8542","position":12,"is_corresponding":false},{"id":86210,"name":"Beate Ritz","orcid":"0000-0001-6976-7339","position":13,"is_corresponding":false},{"id":242548,"name":"Lars Bertram","orcid":"0000-0002-0108-124X","position":14,"is_corresponding":false},{"id":936112,"name":"Christina M. Lill","orcid":"0000-0002-2805-1307","position":15,"is_corresponding":false},{"id":936110,"name":"Olena Ohlei","orcid":"0009-0003-7721-6803","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-19T02:01:37.886033Z","pmid":"38863574","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":[]}