{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:47:11Z","timestamp":1792154831132,"version":"4.4.0"},"reference-count":32,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Science Funds of China","award":["No.81271118 and No. 81600849"],"award-info":[{"award-number":["No.81271118 and No. 81600849"]}]},{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2024NSFSC0649"],"award-info":[{"award-number":["2024NSFSC0649"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Research and Develop Program, West China Hospital of Stomatology Sichuan University","award":["No. RD-03-202301"],"award-info":[{"award-number":["No. RD-03-202301"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The Cleft Palate Craniofacial Journal"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify susceptibility loci for nonsyndromic cleft lip and\/or palate with cleft alveolus involvement and to elucidate subtype-specific regulatory mechanisms in a Chinese population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Subtype-stratified case-control targeted association analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Tertiary medical center for orofacial cleft treatment in western China.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients, Participants<\/jats:title>\n                    <jats:p>A total of 3009 unrelated Chinese individuals from two previously generated Genome-wide association study datasets, comprising 445 cases with cleft lip extending through the alveolus without palatal involvement (CLCA), 309 cases with cleft lip and palate extending through the alveolus (CLPCA), and 754 combined CL\/P with cleft alveolus (CL\/PCA) cases, along with unaffected controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measure(s)<\/jats:title>\n                    <jats:p>\n                      Single nucleotide polymorphisms associations with CLCA, CLPCA, and combined CL\/PCA phenotypes at Bonferroni-corrected significance (P\u2009&lt;\u20093.65\u2009\u00d7\u200910\n                      <jats:sup>\u22126<\/jats:sup>\n                      ), with functional annotation integrating ENCODE chromatin states, Hi-C interactions, and GTEx eQTL data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three SNPs (rs10863790, rs2064163, rs4880224) reached study-wide significance in the combined CL\/PCA and CLCA subgroups but not in CLPCA. rs10863790 showed the highest population attributable risk in CLCA (29.63%). All three variants overlap NHEK-active enhancers and regulate craniofacial development genes (\n                      <jats:italic toggle=\"yes\">IRF6, UTP25, TRAF3IP3, BNIP3, JAKMIP3, PPP2R2D<\/jats:italic>\n                      ) through chromatin looping, pluripotency factor binding, and FOX family transcription factor recruitment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings reveal pronounced genetic heterogeneity between CLCA and CLPCA subtypes, underscoring the necessity of subtype-stratified approaches for precision medicine in orofacial cleft management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10556656261495252","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:02:06Z","timestamp":1791997326000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Heterogeneity in Cleft Lip and\/or Palate With Alveolar Cleft: A Targeted Analysis of NHEK-Active Enhancer Variants"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3513-4222","authenticated-orcid":false,"given":"Yan","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1496-0478","authenticated-orcid":false,"given":"Lingfeng","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixian","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0129-0367","authenticated-orcid":false,"given":"Zhonglin","family":"Jia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4103\/2231-0746.110083"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60695-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4103\/jfmpc.jfmpc_472_20"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1597\/15-148"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/2000656X.2016.1263202"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy402"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0301-0503(76)80013-6"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx012"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.333"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.506"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520943867"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241006"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.03.129"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1903"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-022-00194-0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345231165210"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.11.008"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng985"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20598"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7414"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008357"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.229102"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.135350.111"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.036"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520904018"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw104"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517703580"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008222"}],"container-title":["The Cleft Palate Craniofacial Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10556656261495252","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10556656261495252","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10556656261495252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:53:16Z","timestamp":1792151596000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10556656261495252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":32,"alternative-id":["10.1177\/10556656261495252"],"URL":"https:\/\/doi.org\/10.1177\/10556656261495252","relation":{},"ISSN":["1055-6656","1545-1569"],"issn-type":[{"value":"1055-6656","type":"print"},{"value":"1545-1569","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"article-number":"10556656261495252"}}