{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:27:41Z","timestamp":1740130061678,"version":"3.37.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970569","82170896","32170616"],"award-info":[{"award-number":["31970569","82170896","32170616"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Basic Research Program Shaanxi Province","award":["2021JC-02"],"award-info":[{"award-number":["2021JC-02"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shaanxi Provincial Key Research and Development Project","award":["2019ZDLSF01-09"],"award-info":[{"award-number":["2019ZDLSF01-09"]}]},{"name":"Natural Science Foundation of Zhejing Province","award":["LWY20H060001"],"award-info":[{"award-number":["LWY20H060001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Thyroid dysfunction is a common endocrine disease measured by thyroid-stimulating hormone (TSH) level. Although &amp;gt;70 genetic loci associated with TSH have been reported through genome-wide association studies (GWASs), the variants can only explain a small fraction of the thyroid function heritability. To identify novel candidate genes for thyroid function, we conducted the first large-scale transcriptome-wide association study (TWAS) for thyroid function using GWAS-summary data for TSH levels in up to 119\u2009715 individuals combined with precomputed gene expression weights of six panels from four tissue types. The candidate genes identified by TWAS were further validated by TWAS replication and gene expression profiles. We identified 74 conditionally independent genes significantly associated with thyroid function, such as PDE8B (P\u2009=\u20091.67\u2009\u00d7\u200910\u2212282), PDE10A (P\u2009=\u20097.61\u2009\u00d7\u200910\u2212119), NR3C2 (P\u2009=\u20091.50\u2009\u00d7\u200910\u221292) and CAPZB (P\u2009=\u20093.13\u2009\u00d7\u200910\u221279). After TWAS replication using UKBB datasets, 26 genes were replicated for significant associations with thyroid-relevant diseases\/traits. Among them, 16 genes were causal for their associations to thyroid-relevant diseases\/traits and further validated in differential expression analyses, including two novel genes (MFSD6 and RBM47) that did not implicate in previous GWASs. Enrichment analyses detected several pathways associated with thyroid function, such as the cAMP signaling pathway (P\u2009=\u20097.27\u2009\u00d7\u200910\u22124), hemostasis (P\u2009=\u20093.74\u2009\u00d7\u200910\u22124), and platelet activation, signaling and aggregation (P\u2009=\u20099.98\u2009\u00d7\u200910\u22124). Our study identified multiple candidate genes and pathways associated with thyroid function, providing novel clues for revealing the genetic mechanisms of thyroid function and disease.<\/jats:p>","DOI":"10.1093\/hmg\/ddab371","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T20:11:19Z","timestamp":1640290279000},"page":"1871-1883","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptome-wide association study identifies multiple genes and pathways associated with thyroid function"],"prefix":"10.1093","volume":"31","author":[{"given":"Xin","family":"Ke","sequence":"first","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"School of Life Science and Technology, Xi'an Jiaotong University , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics , , Xi'an, Shaanxi, PR China"},{"name":"Honghui Hospital, Xi'an Jiaotong University , , Xi'an, Shaanxi, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Yao","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy , , Xi'an 710004, Shaanxi, PR China"},{"name":"The Second Affiliated Hospital, Xi'an Jiaotong University , , Xi'an 710004, Shaanxi, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"School of Life Science and Technology, Xi'an Jiaotong University , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-Yuan","family":"Duan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"School of Life Science and Technology, Xi'an Jiaotong University , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nai-Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"School of Life Science and Technology, Xi'an Jiaotong University , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"School of Life Science and Technology, Xi'an Jiaotong University , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7062-3025","authenticated-orcid":false,"given":"Tie-Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"School of Life Science and Technology, Xi'an Jiaotong University , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy , , Xi'an 710004, Shaanxi, PR China"},{"name":"The Second Affiliated Hospital, Xi'an Jiaotong University , , Xi'an 710004, Shaanxi, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan-Shan","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"School of Life Science and Technology, Xi'an Jiaotong University , Biomedical Informatics & Genomics Center, , Xi'an, Shaanxi, PR China , 710049"},{"name":"Research Institute of Xi'an Jiaotong University , Hangzhou, Zhejiang, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dageng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics , , Xi'an, Shaanxi, PR China"},{"name":"Honghui 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"2022060611293402600_ref1","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/S0140-6736(11)60276-6","article-title":"Subclinical thyroid disease","volume":"379","author":"Cooper","year":"2012","journal-title":"Lancet"},{"key":"2022060611293402600_ref2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1210\/er.2006-0043","article-title":"The clinical significance of subclinical thyroid dysfunction","volume":"29","author":"Biondi","year":"2008","journal-title":"Endocr. 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