{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:40:21Z","timestamp":1776325221753,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"publisher","award":["R-913-200-098-263"],"award-info":[{"award-number":["R-913-200-098-263"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"publisher","award":["MOE2016-T2-2-029"],"award-info":[{"award-number":["MOE2016-T2-2-029"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"publisher","award":["MOE2018-T2-1-046"],"award-info":[{"award-number":["MOE2018-T2-1-046"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"publisher","award":["MOE2018-T2-2-006"],"award-info":[{"award-number":["MOE2018-T2-2-006"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["11871474"],"award-info":[{"award-number":["11871474"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["61701547"],"award-info":[{"award-number":["61701547"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hong Kong Research Grant Council","award":["12301417"],"award-info":[{"award-number":["12301417"]}]},{"name":"Hong Kong Research Grant Council","award":["16307818"],"award-info":[{"award-number":["16307818"]}]},{"name":"Hong Kong Research Grant Council","award":["16301419"],"award-info":[{"award-number":["16301419"]}]},{"name":"Hong Kong Research Grant Council","award":["DMS-1916199"],"award-info":[{"award-number":["DMS-1916199"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Transcriptome-wide association studies (TWASs) integrate expression quantitative trait loci (eQTLs) studies with genome-wide association studies (GWASs) to prioritize candidate target genes for complex traits. Several statistical methods have been recently proposed to improve the performance of TWASs in gene prioritization by integrating the expression regulatory information imputed from multiple tissues, and made significant achievements in improving the ability to detect gene-trait associations. Unfortunately, most existing multi-tissue methods focus on prioritization of candidate genes, and cannot directly infer the specific functional effects of candidate genes across different tissues. Here, we propose a tissue-specific collaborative mixed model (TisCoMM) for TWASs, leveraging the co-regulation of genetic variations across different tissues explicitly via a unified probabilistic model. TisCoMM not only performs hypothesis testing to prioritize gene-trait associations, but also detects the tissue-specific role of candidate target genes in complex traits. To make full use of widely available GWASs summary statistics, we extend TisCoMM to use summary-level data, namely, TisCoMM-S2. Using extensive simulation studies, we show that type I error is controlled at the nominal level, the statistical power of identifying associated genes is greatly improved, and the false-positive rate (FPR) for non-causal tissues is well controlled at decent levels. We further illustrate the benefits of our methods in applications to summary-level GWASs data of 33 complex traits. Notably, apart from better identifying potential trait-associated genes, we can elucidate the tissue-specific role of candidate target genes. The follow-up pathway analysis from tissue-specific genes for asthma shows that the immune system plays an essential function for asthma development in both thyroid and lung tissues.<\/jats:p>","DOI":"10.1093\/nar\/gkaa767","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T15:14:18Z","timestamp":1599146058000},"page":"e109-e109","source":"Crossref","is-referenced-by-count":24,"title":["A tissue-specific collaborative mixed model for jointly analyzing multiple tissues in transcriptome-wide association studies"],"prefix":"10.1093","volume":"48","author":[{"given":"Xingjie","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Statistics, Nanjing University of Finance and Economics, Nanjing, China"},{"name":"Centre for Quantitative Medicine, Health Services & Systems Research, Duke-NUS Medical School, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoran","family":"Chai","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Genomics (ICG)\u00a0& Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, China"},{"name":"School of Medicine, National University of Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Centre for Quantitative Medicine, Health Services & Systems Research, Duke-NUS Medical School, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Centre for Quantitative Medicine, Health Services & Systems Research, Duke-NUS Medical School, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuling","family":"Jiao","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics, and Hubei Key Laboratory of Computational Science, Wuhan University, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoyue","family":"Chen","sequence":"additional","affiliation":[{"name":"School of International Studies, Zhejiang University, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Statistics and Actuarial Science, University of Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4407-3055","authenticated-orcid":false,"given":"Can","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Mathematics, The Hong Kong University of Science and Technology, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5707-2078","authenticated-orcid":false,"given":"Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"Centre for Quantitative Medicine, Health Services & Systems Research, Duke-NUS Medical School, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,9,26]]},"reference":[{"key":"2020110419230140400_B1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ajhg.2017.06.005","article-title":"10 years of GWAS discovery: biology, function, and translation","volume":"101","author":"Visscher","year":"2017","journal-title":"Am. 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