{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:18:48Z","timestamp":1788812328858,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81830031"],"award-info":[{"award-number":["81830031"]}],"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":["82270496"],"award-info":[{"award-number":["82270496"]}],"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":["81970969"],"award-info":[{"award-number":["81970969"]}],"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":["82001088"],"award-info":[{"award-number":["82001088"]}],"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":["82101054"],"award-info":[{"award-number":["82101054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20220309"],"award-info":[{"award-number":["BK20220309"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The BCL\u20102 family is crucial for cell death regulation and is involved in development, tissue homeostasis, and immunity. This study aimed to investigate the association between genetic variants in BCL\u20102 family genes and non\u2010syndromic cleft lip with or without cleft palate (NSCL\/P) risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A two\u2010stage case\u2013control study was conducted in this association study. Gene\u2010based analysis using Multi\u2010marker Analysis of GenoMic Annotation was performed in the first stage cohort, which included 565 cases and 1269 controls. A logistic regression model was employed to assess the effect of single nucleotide polymorphisms (SNPs) on susceptibility to NSCL\/P. Candidate SNPs were replicated by extra dbGaP case\u2010parent trios. Haploreg, RegulomeDB, and UCSC Genome Browser were used to identify enhancer effects of promising SNPs. Bulk RNA sequencing data obtained from the Gene Expression Omnibus was used to identify co\u2010expressed genes. Single\u2010cell RNA sequencing dataset was used to infer the cell population of the candidate gene. The \u201cMonocle\u201d package was used to analyze the pseudotime cell trajectories.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rs3943258 located in the enhancer region was associated with the risk of NSCL\/P (<jats:italic>P<\/jats:italic><jats:sub>meta<\/jats:sub>\u2009=\u20095.66\u2009\u00d7\u200910<jats:sup>\u221204<\/jats:sup>) and exhibited an eQTL effect for <jats:italic>BCL2<\/jats:italic> (<jats:italic>P<\/jats:italic>\u2009=\u20093.96\u2009\u00d7\u200910<jats:sup>\u221202<\/jats:sup>). Co\u2010expression and pathway enrichment analysis revealed that genes related to <jats:italic>Bcl2<\/jats:italic> were significantly enriched in the PI3K\u2010Akt signaling pathway, MAPK signaling pathway, and Wnt signaling pathway. Five cell clusters were identified in single\u2010cell RNA sequencing, and <jats:italic>Bcl2<\/jats:italic> was mainly located in the mesenchyme.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The rs3943258 located within <jats:italic>BCL2<\/jats:italic> was probably related to NSCL\/P susceptibility.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2288","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T14:57:59Z","timestamp":1702911479000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetic variants in <scp>BCL<\/scp>\u20102 family genes influence the risk of non\u2010syndromic cleft lip with or without cleft palate"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0729-0875","authenticated-orcid":false,"given":"Xing","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guirong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minxuan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyue","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangbo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory of Reproductive Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatology Hospital of Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory of Reproductive Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2019.10.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1283-6"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1534-5807(01)00083-1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab447"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.01.025"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1597\/05-167"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3722"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37181"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5294"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2004.11.022"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.010"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1508"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-102822-100509"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.048"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PRS.0000105342.08168.13"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2017.03.025"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2008.41.1.011"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20646"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aav7666"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.04.036"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72688"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dib.2017.05.003"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.187369"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.174888"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjoms.2015.05.021"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2360"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034508327868"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20055"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.12.016"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.170"},{"issue":"7","key":"e_1_2_11_34_1","first-page":"S11","article-title":"Global birth prevalence of orofacial clefts: A systematic review","volume":"98","author":"Panamonta V.","year":"2015","journal-title":"Journal of the Medical Association of Thailand = Chotmaihet Thangphaet"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6093263"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11478"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.03.129"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjoms.2020.07.009"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112310"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40315"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14364"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb0119"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2019.111734"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.2288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T05:25:00Z","timestamp":1720675500000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.2288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,18]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/bdr2.2288"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.2288","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,18]]},"assertion":[{"value":"2023-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2288"}}