Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity

Yanqin Yu, Xianbo Zuo, Miao He, Jinping Gao, Yuchuan Fu, Chuanqi Qin, Liuyan Meng, Wenjun Wang, Yaling Song, Yong Cheng, Fusheng Zhou, Gang Chen, Xiaodong Zheng, Xinhuan Wang, Bo Liang, Zhengwei Zhu, Xiazhou Fu, Yujun Sheng, Jiebing Hao, Zhongyin LiuHansong Yan, Elisabeth Mangold, Ingo Ruczinski, Jianjun Liu, Mary L. Marazita, Kerstin U. Ludwig, Terri H. Beaty, Xuejun Zhang, Liangdan Sun, Zhuan Bian

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Non-syndromic cleft lip with palate (NSCLP) is the most serious sub-phenotype of non-syndromic orofacial clefts (NSOFC), which are the most common craniofacial birth defects in humans. Here we conduct a GWAS of NSCLP with multiple independent replications, totalling 7,404 NSOFC cases and 16,059 controls from several ethnicities, to identify new NSCLP risk loci, and explore the genetic heterogeneity between sub-phenotypes of NSOFC. We identify 41 SNPs within 26 loci that achieve genome-wide significance, 14 of which are novel (RAD54B, TMEM19, KRT18, WNT9B, GSC/DICER1, PTCH1, RPS26, OFCC1/TFAP2A, TAF1B, FGF10, MSX1, LINC00640, FGFR1 and SPRY1). These 26 loci collectively account for 10.94% of the heritability for NSCLP in Chinese population. We find evidence of genetic heterogeneity between the sub-phenotypes of NSOFC and among different populations. This study substantially increases the number of genetic susceptibility loci for NSCLP and provides important insights into the genetic aetiology of this common craniofacial malformation.

Original languageEnglish (US)
Article number14364
JournalNature communications
StatePublished - Feb 24 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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