{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:04:02Z","timestamp":1785258242711,"version":"3.55.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Universities of China Pharmaceutical University","award":["2632023FY04"],"award-info":[{"award-number":["2632023FY04"]}]},{"name":"Fundamental Research Funds for the Central Universities of China Pharmaceutical University","award":["2632023FY05"],"award-info":[{"award-number":["2632023FY05"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273735"],"award-info":[{"award-number":["82273735"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304252"],"award-info":[{"award-number":["82304252"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473737"],"award-info":[{"award-number":["82473737"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science Foundation for Young Scientists of China","award":["82404380"],"award-info":[{"award-number":["82404380"]}]},{"name":"2024 National Key Research on Multi-Target Natural Drugs","award":["SKLNMZZ2024JS32"],"award-info":[{"award-number":["SKLNMZZ2024JS32"]}]},{"DOI":"10.13039\/501100011330","name":"Key Laboratory of Scientific and Engineering Computing","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011330","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Frontiers Science Center of Modern Analysis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mendelian randomization (MR) leverages genetic variants as instrumental variables to infer causal relationships between molecular traits and diseases, however, identifying the specific causal genes underlying disease risk remains challenging. Here, we present MULTI (Multi-tissue Unified Likelihood-based Transcriptomic Integration), a Bayesian MR framework that integrates genetic information across tissues to improve the accuracy of causal inference. MULTI yields reliable estimates even when the number of instruments in a single tissue is limited, and further increases statistical power by adaptively integrating information from similar tissues without inflating type I error rates. Extensive simulations confirm its robustness under diverse genetic architectures, and applications to real datasets demonstrate its capacity to reveal tissue-specific causal mechanisms and coordinated cross-tissue regulation. MULTI offers a practical and extensible framework for elucidating the molecular architecture of complex human diseases.<\/jats:p>","DOI":"10.1093\/bib\/bbag414","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T11:49:50Z","timestamp":1783770590000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi-tissue integrated Mendelian randomization method identifies disease risk genes"],"prefix":"10.1093","volume":"27","author":[{"given":"Yu","family":"Cheng","sequence":"first","affiliation":[{"name":"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University , No. 639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhan","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University , No. 639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-2641","authenticated-orcid":false,"given":"Xinjia","family":"Ruan","sequence":"additional","affiliation":[{"name":"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University , No. 639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghua","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University , No. 639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University , No. 639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4207-8651","authenticated-orcid":false,"given":"Tiantian","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University , No. 639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8673-2321","authenticated-orcid":false,"given":"Fangrong","family":"Yan","sequence":"additional","affiliation":[{"name":"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University , No. 639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"2026072812460684200_ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","article-title":"\u2018Mendelian randomization\u2019: can genetic epidemiology contribute to understanding environmental determinants of disease?","volume":"32","author":"Smith","year":"2003","journal-title":"Int J Epidemiol"},{"key":"2026072812460684200_ref2","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/ije\/dyh132","article-title":"Mendelian randomization: prospects, potentials, and limitations","volume":"33","author":"Smith","year":"2004","journal-title":"Int J Epidemiol"},{"key":"2026072812460684200_ref3","doi-asserted-by":"publisher","first-page":"i206","DOI":"10.1093\/bioinformatics\/btv240","article-title":"Identification of causal genes for complex traits","volume":"31","author":"Hormozdiari","year":"2015","journal-title":"Bioinformatics"},{"key":"2026072812460684200_ref4","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1038\/s41588-021-00945-5","article-title":"An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci","volume":"53","author":"Mountjoy","year":"2021","journal-title":"Nat Genet"},{"key":"2026072812460684200_ref5","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/s41588-024-01994-2","article-title":"Fine-mapping causal tissues and genes at disease-associated loci","volume":"57","author":"Strober","year":"2025","journal-title":"Nat Genet"},{"key":"2026072812460684200_ref6","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"Consortium, G.T","year":"2020","journal-title":"Science"},{"key":"2026072812460684200_ref7","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/ng.3506","article-title":"Integrative approaches for large-scale transcriptome-wide association studies","volume":"48","author":"Gusev","year":"2016","journal-title":"Nat Genet"},{"key":"2026072812460684200_ref8","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/s41588-019-0385-z","article-title":"Opportunities and challenges for transcriptome-wide association studies","volume":"51","author":"Wainberg","year":"2019","journal-title":"Nat Genet"},{"key":"2026072812460684200_ref9","doi-asserted-by":"publisher","first-page":"4361","DOI":"10.1038\/s41467-018-06805-x","article-title":"Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes","volume":"9","author":"Zhu","year":"2018","journal-title":"Nat Commun"},{"key":"2026072812460684200_ref10","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"key":"2026072812460684200_ref11","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1016\/j.ajhg.2018.03.021","article-title":"Estimation of genetic correlation via linkage disequilibrium score regression and genomic restricted maximum likelihood","volume":"102","author":"Ni","year":"2018","journal-title":"Am J Hum Genet"},{"key":"2026072812460684200_ref12","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1214\/17-AOAS1046","article-title":"Bayesian large-scale multiple regression with summary statistics from genome-wide association studies","volume":"11","author":"Zhu","year":"2017","journal-title":"Ann Appl Stat"},{"key":"2026072812460684200_ref13","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaf214","article-title":"Accounting for the impact of rare variants on causal inference with RARE: a novel multivariable Mendelian randomization method","volume":"26","author":"Cheng","year":"2025","journal-title":"Brief Bioinform"},{"key":"2026072812460684200_ref14","doi-asserted-by":"publisher","first-page":"e1007889","DOI":"10.1371\/journal.pgen.1007889","article-title":"Integrating predicted transcriptome from multiple tissues improves association detection","volume":"15","author":"Barbeira","year":"2019","journal-title":"PLoS Genet"},{"key":"2026072812460684200_ref15","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/s41588-019-0345-7","article-title":"A statistical framework for cross-tissue transcriptome-wide association analysis","volume":"51","author":"Hu","year":"2019","journal-title":"Nat Genet"},{"key":"2026072812460684200_ref16","first-page":"453","article-title":"The variational Bayesian EM algorithm for incomplete data: with application to scoring graphical model structures","volume":"7","author":"Beal","year":"2003","journal-title":"Bayesian Statistics"},{"key":"2026072812460684200_ref17","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1002\/gepi.22522","article-title":"Bias correction for inverse variance weighting Mendelian randomization","volume":"47","author":"Mounier","year":"2023","journal-title":"Genet Epidemiol"},{"key":"2026072812460684200_ref18","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s10654-017-0276-5","article-title":"Erratum to: interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"2026072812460684200_ref19","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet Epidemiol"},{"key":"2026072812460684200_ref20","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1093\/ije\/dyx102","article-title":"Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption","volume":"46","author":"Hartwig","year":"2017","journal-title":"Int J Epidemiol"},{"key":"2026072812460684200_ref21","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/s41467-019-14156-4","article-title":"A robust and efficient method for Mendelian randomization with hundreds of genetic variants","volume":"11","author":"Burgess","year":"2020","journal-title":"Nat Commun"},{"key":"2026072812460684200_ref22","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12964-019-0341-7","article-title":"DRAM1 regulates autophagy and cell proliferation via inhibition of the phosphoinositide 3-kinase-Akt-mTOR-ribosomal protein S6 pathway","volume":"17","author":"Lu","year":"2019","journal-title":"Cell Commun Signal"},{"key":"2026072812460684200_ref23","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.cell.2006.05.034","article-title":"DRAM, a p53-induced modulator of autophagy, is critical for apoptosis","volume":"126","author":"Crighton","year":"2006","journal-title":"Cell"},{"key":"2026072812460684200_ref24","doi-asserted-by":"publisher","first-page":"E925","DOI":"10.1152\/ajpendo.00294.2015","article-title":"Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway","volume":"309","author":"Sun","year":"2015","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2026072812460684200_ref25","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.immuni.2019.11.013","article-title":"Immune sensing of cell death through recognition of histone sequences by C-type lectin-receptor-2d causes inflammation and tissue injury","volume":"52","author":"Lai","year":"2020","journal-title":"Immunity"},{"key":"2026072812460684200_ref26","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1188816","article-title":"Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond","volume":"14","author":"Motta","year":"2023","journal-title":"Front Physiol"},{"key":"2026072812460684200_ref27","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1160\/TH13-02-0179","article-title":"Role of plasma kallikrein in diabetes and metabolism","volume":"110","author":"Feener","year":"2013","journal-title":"Thromb Haemost"},{"key":"2026072812460684200_ref28","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1001\/jamaneurol.2020.5257","article-title":"Identification of candidate Parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets","volume":"78","author":"Kia","year":"2021","journal-title":"JAMA Neurol"},{"key":"2026072812460684200_ref29","doi-asserted-by":"crossref","article-title":"Integration of eQTL and Parkinson\u2019s disease GWAS data implicates 11 disease genes","author":"Kia","DOI":"10.1101\/627216"},{"key":"2026072812460684200_ref30","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"2026072812460684200_ref31","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"2026072812460684200_ref32","first-page":"51","article-title":"The basal ganglia and disorders of movement: pathophysiological mechanisms","volume":"17","author":"Obeso","year":"2002","journal-title":"News Physiol Sci"},{"key":"2026072812460684200_ref33","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1056\/NEJM198804073181402","article-title":"Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson\u2019s disease. Pathophysiologic and clinical implications","volume":"318","author":"Kish","year":"1988","journal-title":"N Engl J Med"},{"key":"2026072812460684200_ref34","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1016\/j.ajhg.2024.06.012","article-title":"An integrative multi-context Mendelian randomization method for identifying risk genes across human tissues","volume":"111","author":"Lu","year":"2024","journal-title":"Am J Hum Genet"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/27\/4\/bbag414\/70275090\/bbag414.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/27\/4\/bbag414\/70275090\/bbag414.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:46:17Z","timestamp":1785257177000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbag414\/8746112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7,3]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbag414","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,7]]},"article-number":"bbag414"}}