{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:23:04Z","timestamp":1778602984604,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"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":["81102178"],"award-info":[{"award-number":["81102178"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The folate\u2010mediated one\u2010carbon metabolism pathway is thought to play an important role in the etiology of non\u2010syndromic oral clefts (NSOFC), although none of the genes in this pathway has shown significant signals in genome\u2010wide association studies (GWAS). Recent evidence indicated that enhanced understanding could be gained by aggregating multiple SNPs effect simultaneously into polygenic risk score (PRS) to assess its association with disease risks. This study is aimed to assess the association between the genetic effect of folate\u2010mediated one\u2010carbon metabolism pathway and NSOFC risks using PRS based on a case\u2013parent trio design. A total of 297 SNPs mapped from 18 genes in the folate\u2010mediated one\u2010carbon metabolism pathway were aggregated from a GWAS of 2458 case\u2013parent trios recruited from an international consortium. We found a PRS based on the folate\u2010mediated one\u2010carbon metabolism pathway was significant among all NSOFC trios (OR\u00a0=\u00a01.95, 95% CI: 1.66\u20132.28,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a02.39\u00a0\u00d7\u00a010\n                    <jats:sup>\u221216<\/jats:sup>\n                    ), as well as two major subtypes, non\u2010syndromic cleft lip with or without cleft palate (NSCL\/P) trios (OR\u00a0=\u00a01.71, 95% CI: 1.50\u20131.96,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a07.66\u00a0\u00d7\u00a010\n                    <jats:sup>\u221215<\/jats:sup>\n                    ) and non\u2010syndromic cleft palate only (NSCPO) trios (OR\u00a0=\u00a01.51, 95% CI: 1.36\u20131.68,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a02.1\u00a0\u00d7\u00a010\n                    <jats:sup>\u221214<\/jats:sup>\n                    ). Similar results were also observed in further subgroup analyses stratified into Asian and European trios. The averaged PRS of the folate\u2010mediated one\u2010carbon metabolism pathway varied between the NSOFC case group and its comparison group (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05) with higher average PRS in the cases. Moreover, the top 5% pathway PRS group had 2.25 (95% CI: 1.85\u20132.73) times increased NSOFC risk, also 3.09 (95% CI: 2.50\u20133.81) and 2.06 (95% CI: 1.39\u20133.02) times increased risk of NSCL\/P and NSCPO compared to the remainder of the distribution. The results of our study confirmed the folate\u2010mediated one\u2010carbon metabolism pathway was important in controlling risk to NSOFC and this study enhanced evidence towards understanding the genetic risks of NSOFC.\n                  <\/jats:p>","DOI":"10.1111\/odi.14068","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T08:48:36Z","timestamp":1636102116000},"page":"1080-1088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evidence of the folate\u2010mediated one\u2010carbon metabolism pathway genes in controlling the non\u2010syndromic oral clefts risks"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-7955","authenticated-orcid":false,"given":"Siyue","family":"Wang","sequence":"first","affiliation":[{"name":"Peking University Health Science Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayu","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Growth and Development and Section of Orthodontics School of Dentistry University of California  Los Angeles USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfang","family":"Liu","sequence":"additional","affiliation":[{"name":"BaoTou Medical College  Baotou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0162-5355","authenticated-orcid":false,"given":"Mengying","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyong","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5776-3100","authenticated-orcid":false,"given":"Ren","family":"Zhou","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongchen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University School of Stomatology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University School of Stomatology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Peking University School of Stomatology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Peking University School of Stomatology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiqun","family":"Wu","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center  Beijing 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Peking University Health Science Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri H.","family":"Beaty","sequence":"additional","affiliation":[{"name":"School of Public Health Johns Hopkins University  Baltimore Maryland 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