{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T03:42:28Z","timestamp":1781840548014,"version":"3.54.5"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010785","name":"Canada First Research Excellence Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010785","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Colocalization analysis is commonly used to assess whether two or more traits share the same genetic signals identified in genome-wide association studies (GWAS), and is important for prioritizing targets for functional follow-up of GWAS results. Existing colocalization methods can have suboptimal performance when there are multiple causal variants in one genomic locus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We propose SharePro to extend the COLOC framework for colocalization analysis. SharePro integrates linkage disequilibrium (LD) modeling and colocalization assessment by grouping correlated variants into effect groups. With an efficient variational inference algorithm, posterior colocalization probabilities can be accurately estimated. In simulation studies, SharePro demonstrated increased power with a well-controlled false positive rate at a low computational cost. Compared to existing methods, SharePro provided stronger and more consistent colocalization evidence for known lipid-lowering drug target proteins and their corresponding lipid traits. Through an additional challenging case of the colocalization analysis of the circulating abundance of R-spondin 3 GWAS and estimated bone mineral density GWAS, we demonstrated the utility of SharePro in identifying biologically plausible colocalized signals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>SharePro for colocalization analysis is written in Python and openly available at https:\/\/github.com\/zhwm\/SharePro_coloc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae295","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T15:38:15Z","timestamp":1714405095000},"source":"Crossref","is-referenced-by-count":21,"title":["SharePro: an accurate and efficient genetic colocalization method accounting for multiple causal signals"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-8859","authenticated-orcid":false,"given":"Wenmin","family":"Zhang","sequence":"first","affiliation":[{"name":"Quantitative Life Sciences Program, McGill University , Montreal, Quebec H3A 1E3, Canada"},{"name":"Montreal Heart Institute, Universit\u00e9 de Montr\u00e9al , Montreal, Quebec H1T 1C8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-5698","authenticated-orcid":false,"given":"Tianyuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Statistical Sciences, University of Toronto , Toronto, Ontario M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-1204","authenticated-orcid":false,"given":"Robert","family":"Sladek","sequence":"additional","affiliation":[{"name":"Quantitative Life Sciences Program, McGill University , Montreal, Quebec H3A 1E3, Canada"},{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3A 0C7, Canada"},{"name":"Dahdaleh Institute of Genomic Medicine, McGill University , Montreal, Quebec H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-4865","authenticated-orcid":false,"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Quantitative Life Sciences Program, McGill University , Montreal, Quebec H3A 1E3, Canada"},{"name":"School of Computer Science, McGill University , Montreal, Quebec H3A 2A7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2735-4231","authenticated-orcid":false,"given":"Hamed","family":"Najafabadi","sequence":"additional","affiliation":[{"name":"Quantitative Life Sciences Program, McGill University , Montreal, Quebec H3A 1E3, Canada"},{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3A 0C7, Canada"},{"name":"Dahdaleh Institute of Genomic Medicine, McGill University , Montreal, Quebec H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2871-3603","authenticated-orcid":false,"given":"Jos\u00e9e","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Quantitative Life Sciences Program, McGill University , Montreal, Quebec H3A 1E3, Canada"},{"name":"Department of Epidemiology, Biostatistics and Occupational Health, McGill University , McGill College, QC H3A 1Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"2024052100013263600_btae295-B1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"Wnt signaling in bone homeostasis and disease: from human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat Med"},{"key":"2024052100013263600_btae295-B2","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1080\/01621459.2017.1285773","article-title":"Variational inference: a review for statisticians","volume":"112","author":"Blei","year":"2017","journal-title":"J Am Stat Assoc"},{"key":"2024052100013263600_btae295-B3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"2024052100013263600_btae295-B4","doi-asserted-by":"crossref","first-page":"6870","DOI":"10.1038\/s41467-023-42614-7","article-title":"Xmap: cross-population fine-mapping by leveraging genetic diversity and accounting for confounding bias","volume":"14","author":"Cai","year":"2023","journal-title":"Nat Commun"},{"key":"2024052100013263600_btae295-B5","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/ng.3330","article-title":"Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls","volume":"47","author":"Fortune","year":"2015","journal-title":"Nat Genet"},{"key":"2024052100013263600_btae295-B6","doi-asserted-by":"crossref","first-page":"e1004383","DOI":"10.1371\/journal.pgen.1004383","article-title":"Bayesian test for colocalisation between pairs of genetic association studies using summary statistics","volume":"10","author":"Giambartolomei","year":"2014","journal-title":"PLoS Genet"},{"key":"2024052100013263600_btae295-B7","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1534\/genetics.114.167908","article-title":"Identifying causal variants at loci with multiple signals of association","volume":"198","author":"Hormozdiari","year":"2014","journal-title":"Genetics"},{"key":"2024052100013263600_btae295-B8","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.ajhg.2016.10.003","article-title":"Colocalization of GWAS and EQTL signals detects target genes","volume":"99","author":"Hormozdiari","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2024052100013263600_btae295-B9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ajhg.2020.11.012","article-title":"Probabilistic colocalization of genetic variants from complex and molecular traits: promise and limitations","volume":"108","author":"Hukku","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2024052100013263600_btae295-B10","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/joim.12368","article-title":"The WNT system: background and its role in bone","volume":"277","author":"Lerner","year":"2015","journal-title":"J Intern Med"},{"key":"2024052100013263600_btae295-B11","doi-asserted-by":"crossref","first-page":"104543","DOI":"10.1016\/j.ebiom.2023.104543","article-title":"Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease","volume":"90","author":"Li","year":"2023","journal-title":"EBioMedicine"},{"key":"2024052100013263600_btae295-B12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13073-021-00838-6","article-title":"Improved prediction of fracture risk leveraging a genome-wide polygenic risk score","volume":"13","author":"Lu","year":"2021","journal-title":"Genome Med"},{"key":"2024052100013263600_btae295-B13","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1002\/jbmr.4632","article-title":"Identifying causes of fracture beyond bone mineral density: evidence from human genetics","volume":"37","author":"Lu","year":"2022","journal-title":"J Bone Miner Res"},{"key":"2024052100013263600_btae295-B14","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.biopsych.2022.08.015","article-title":"Circulating proteins influencing psychiatric disease: a mendelian randomization study","volume":"93","author":"Lu","year":"2023","journal-title":"Biol Psychiatry"},{"key":"2024052100013263600_btae295-B15","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00109-002-0384-9","article-title":"Lipoprotein lipase: structure, function, regulation, and role in disease","volume":"80","author":"Mead","year":"2002","journal-title":"J Mol Med (Berl)"},{"key":"2024052100013263600_btae295-B16","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41588-018-0302-x","article-title":"An atlas of genetic influences on osteoporosis in humans and mice","volume":"51","author":"Morris","year":"2019","journal-title":"Nat Genet"},{"key":"2024052100013263600_btae295-B17","doi-asserted-by":"crossref","first-page":"4923","DOI":"10.1038\/s41467-021-25124-2","article-title":"Rspo3 is important for trabecular bone and fracture risk in mice and humans","volume":"12","author":"Nilsson","year":"2021","journal-title":"Nat Commun"},{"key":"2024052100013263600_btae295-B18","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/ng.3570","article-title":"Detection and interpretation of shared genetic influences on 42 human traits","volume":"48","author":"Pickrell","year":"2016","journal-title":"Nat Genet"},{"key":"2024052100013263600_btae295-B19","doi-asserted-by":"crossref","first-page":"eabj1541","DOI":"10.1126\/science.abj1541","article-title":"Mapping the proteo-genomic convergence of human diseases","volume":"374","author":"Pietzner","year":"2021","journal-title":"Science"},{"key":"2024052100013263600_btae295-B20","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"Plink: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2024052100013263600_btae295-B21","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41467-019-13921-9","article-title":"A transcriptome-wide mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome","volume":"11","author":"Richardson","year":"2020","journal-title":"Nat Commun"},{"key":"2024052100013263600_btae295-B22","author":"Robinson","year":"2022"},{"key":"2024052100013263600_btae295-B23","doi-asserted-by":"crossref","first-page":"33742","DOI":"10.1074\/jbc.M203215200","article-title":"ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase","volume":"277","author":"Shimizugawa","year":"2002","journal-title":"J Biol Chem"},{"key":"2024052100013263600_btae295-B24","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1001\/jamacardio.2019.3780","article-title":"Apolipoprotein B particles and cardiovascular disease: a narrative review","volume":"4","author":"Sniderman","year":"2019","journal-title":"JAMA Cardiol"},{"key":"2024052100013263600_btae295-B25","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1056\/NEJMoa1105803","article-title":"Effect of a monoclonal antibody to PCSK9 on LDL cholesterol","volume":"366","author":"Stein","year":"2012","journal-title":"N Engl J Med"},{"key":"2024052100013263600_btae295-B26","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41586-018-0175-2","article-title":"Genomic atlas of the human plasma proteome","volume":"558","author":"Sun","year":"2018","journal-title":"Nature"},{"key":"2024052100013263600_btae295-B27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","article-title":"Plasma proteomic associations with genetics and health in the UK biobank","volume":"622","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"2024052100013263600_btae295-B28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJMoa1307095","article-title":"Loss-of-function mutations in apoc3, triglycerides, and coronary disease","volume":"371","author":"TG, HDL Working Group of the Exome Sequencing Project National Heart Lung, and Blood Institute","year":"2014","journal-title":"N Engl J Med"},{"key":"2024052100013263600_btae295-B29","first-page":"2339","article-title":"Spike and slab variational inference for multi-task and multiple kernel learning","volume":"24","author":"Titsias","year":"2011","journal-title":"Adv Neural Inf Process Syst"},{"key":"2024052100013263600_btae295-B30","doi-asserted-by":"crossref","first-page":"e1008720","DOI":"10.1371\/journal.pgen.1008720","article-title":"Eliciting priors and relaxing the single causal variant assumption in colocalisation analyses","volume":"16","author":"Wallace","year":"2020","journal-title":"PLoS Genet"},{"key":"2024052100013263600_btae295-B31","doi-asserted-by":"crossref","first-page":"e1009440","DOI":"10.1371\/journal.pgen.1009440","article-title":"A more accurate method for colocalisation analysis allowing for multiple causal variants","volume":"17","author":"Wallace","year":"2021","journal-title":"PLoS Genet"},{"key":"2024052100013263600_btae295-B32","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1111\/rssb.12388","article-title":"A simple new approach to variable selection in regression, with application to genetic fine mapping","volume":"82","author":"Wang","year":"2020","journal-title":"J R Stat Soc Series B Stat Methodol"},{"key":"2024052100013263600_btae295-B33","doi-asserted-by":"crossref","first-page":"e1006646","DOI":"10.1371\/journal.pgen.1006646","article-title":"Integrating molecular QTL data into genome-wide genetic association analysis: probabilistic assessment of enrichment and colocalization","volume":"13","author":"Wen","year":"2017","journal-title":"PLoS Genet"},{"key":"2024052100013263600_btae295-B34","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: a tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am J Hum Genet"},{"key":"2024052100013263600_btae295-B35","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ng.2213","article-title":"Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits","volume":"44","author":"Yang","year":"2012","journal-title":"Nat Genet"},{"key":"2024052100013263600_btae295-B36","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s42255-023-00742-w","article-title":"Proteome-wide mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on covid-19 severity","volume":"5","author":"Yoshiji","year":"2023","journal-title":"Nat Metab"},{"key":"2024052100013263600_btae295-B37","author":"Yuan","year":"2023"},{"key":"2024052100013263600_btae295-B38","doi-asserted-by":"crossref","first-page":"e1011104","DOI":"10.1371\/journal.pgen.1011104","article-title":"Sparsepro: an efficient fine-mapping method integrating summary statistics and functional annotations","volume":"19","author":"Zhang","year":"2023","journal-title":"PLoS Genet"},{"key":"2024052100013263600_btae295-B39","author":"Zhang","year":"2023"},{"key":"2024052100013263600_btae295-B40","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/s41588-020-0682-6","article-title":"Phenome-wide mendelian randomization mapping the influence of the plasma proteome on complex diseases","volume":"52","author":"Zheng","year":"2020","journal-title":"Nat Genet"},{"key":"2024052100013263600_btae295-B41","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.ajhg.2022.04.001","article-title":"Combining evidence from mendelian randomization and colocalization: review and comparison of approaches","volume":"109","author":"Zuber","year":"2022","journal-title":"Am J Hum Genet"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btae295\/57364690\/btae295.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/5\/btae295\/57769583\/btae295.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/5\/btae295\/57769583\/btae295.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T20:02:16Z","timestamp":1716235336000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btae295\/7660541"}},"subtitle":[],"editor":[{"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btae295","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.07.24.550431","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5,1]]},"published":{"date-parts":[[2024,4,30]]},"article-number":"btae295"}}