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Biol."],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Genome\u2010wide association studies (GWAS) have identified thousands of genomic non\u2010coding variants statistically associated with many human traits and diseases, including cancer. However, the functional interpretation of these non\u2010coding variants remains a significant challenge in the post\u2010GWAS era. Alternative polyadenylation (APA) plays an essential role in post\u2010transcriptional regulation for most human genes. By employing different poly(A) sites, genes can either shorten or extend the 3\u2032\u2010UTRs that contain <jats:italic>cis<\/jats:italic>\u2010regulatory elements such as miRNAs or RNA\u2010binding protein binding sites. Therefore, APA can affect the mRNA stability, translation, and cellular localization of proteins. Population\u2010scale studies have revealed many inherited genetic variants that potentially impact APA to further influence disease susceptibility and phenotypic diversity, but systematic computational investigations to delineate the connections are in their earliest states.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we discuss the evolving definitions of the genetic basis of APA and the modern genomics tools to identify, characterize, and validate the genetic influences of APA events in human populations. We also explore the emerging and surprisingly complex molecular mechanisms that regulate APA and summarize the genetic control of APA that is associated with complex human diseases and traits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>APA is an intermediate molecular phenotype that can translate human common non\u2010coding variants to individual phenotypic variability and disease susceptibility.<\/jats:p><\/jats:sec>","DOI":"10.15302\/j-qb-021-0252","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T01:55:40Z","timestamp":1620266140000},"page":"44-54","source":"Crossref","is-referenced-by-count":5,"title":["Population\u2010scale genetic control of alternative polyadenylation and its association with human diseases"],"prefix":"10.1002","volume":"10","author":[{"given":"Lei","family":"Li","sequence":"first","affiliation":[{"name":"<!--1--> Institute of Systems and Physical Biology Shenzhen Bay Laboratory Shenzhen 518055 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumei","family":"Li","sequence":"additional","affiliation":[{"name":"<!--2--> Division of Computational Biomedicine Department of Biological Chemistry School of Medicine University of California Irvine CA 92697 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xudong","family":"Zou","sequence":"additional","affiliation":[{"name":"<!--1--> Institute of Systems and Physical Biology Shenzhen Bay Laboratory Shenzhen 518055 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuduan","family":"Peng","sequence":"additional","affiliation":[{"name":"<!--2--> Division of Computational Biomedicine Department of Biological Chemistry School of Medicine University of California Irvine CA 92697 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Cui","sequence":"additional","affiliation":[{"name":"<!--2--> Division of Computational Biomedicine Department of Biological Chemistry School of Medicine University of California Irvine CA 92697 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric J.","family":"Wagner","sequence":"additional","affiliation":[{"name":"<!--3--> Department of Biochemistry &amp; Molecular Biology University of Texas Medical Branch Galveston TX 77555 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"<!--2--> Division of Computational Biomedicine Department of Biological Chemistry School of Medicine University of California Irvine CA 92697 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010genet\u2010120116\u2010024704"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2288"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.132563.111"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.116"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a034728"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14321"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.11.002"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.04.017"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1158"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20160126"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6274"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3795"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.139"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.13.2694"},{"key":"e_1_2_9_16_2","first-page":"5226","article-title":"Polymorphism in the N\u2010acetyltransferase 1 (NAT1) polyadenylation signal: association of NAT1*10 allele with higher N\u2010acetylation activity in bladder and colon tissue.","volume":"55","author":"Bell D. 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