{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:44:57Z","timestamp":1787028297457,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:00:00Z","timestamp":1550188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Dental and Craniofacial Research","award":["U01-DE-018993"],"award-info":[{"award-number":["U01-DE-018993"]}]},{"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"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573225"],"award-info":[{"award-number":["81573225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7172115"],"award-info":[{"award-number":["7172115"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Peking University Health Science Center Interdisciplinary Research Fund","award":["BMU2017MX018"],"award-info":[{"award-number":["BMU2017MX018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Non-syndromic cleft lip with or without cleft palate (NSCL\/P) is one of common birth defects in China, with genetic and environmental components contributing to the etiology. Genome wide association studies (GWASs) have identified SPRY1 and SPRY2 to be associated with NSCL\/P among Chinese populations. This study aimed to further explore potential genetic effect and gene\u2014environment interaction among SPRY genes based on haplotype analysis, using 806 Chinese case\u2014parent NSCL\/P trios drawn from an international consortium which conducted a genome-wide association study. After the process of quality control, 190 single nucleotide polymorphisms (SNPs) of SPRY genes were included for analyses. Haplotype and haplotype\u2014environment interaction analyses were conducted in Population-Based Association Test (PBAT) software. A 2-SNP haplotype and three 3-SNP haplotypes showed a significant association with the risk of NSCL\/P after Bonferroni correction (corrected significance level = 2.6 \u00d7 10\u22124). Moreover, haplotype\u2014environment interaction analysis identified these haplotypes respectively showing statistically significant interactions with maternal multivitamin supplementation or maternal environmental tobacco smoke. This study showed SPRY2 to be associated with NSCL\/P among the Chinese population through not only gene effects, but also a gene\u2014environment interaction, highlighting the importance of considering environmental exposures in the genetic etiological study of NSCL\/P.<\/jats:p>","DOI":"10.3390\/ijerph16040557","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:54:21Z","timestamp":1550192061000},"page":"557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Haplotype and Haplotype-Environment Interaction Analysis Revealed Roles of SPRY2 for NSCL\/P among Chinese Populations"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5776-3100","authenticated-orcid":false,"given":"Ren","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0162-5355","authenticated-orcid":false,"given":"Mengying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchen","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibo","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Stomatology, Peking University, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongping","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Peking University, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terri H.","family":"Beaty","sequence":"additional","affiliation":[{"name":"School of Public Health, Johns Hopkins University, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1597\/05-167","article-title":"Asian oral-facial cleft birth prevalence","volume":"43","author":"Cooper","year":"2006","journal-title":"Cleft Palate-Craniofac. 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