Genome-wide meta-analyses identify 5 new risk loci for nonsyndromic orofacial clefts in the Chinese Han population

Nonsyndromic orofacial clefts (NSOFCs) are the common craniofacial birth malformations in humans and are generally classified as nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Genome-wide association studies (GWASs) of NSOFCs have demonstrated multiple risk loci and candidate genes; however, published risk factors are able to explain only a small fraction for the NSOFC heritability in all populations. Here we performed GWASs and genome-wide meta-analyses of NSCL/P and NSCPO, totalling 6,812 NSCL/P cases, 2,614 NSCPO cases, and 19,165 controls from the Chinese Han population. We identified 47 risk loci with genome-wide Pmeta-value < 5.0×10-8, 5 loci (1p32.1, 3p14.1, 3p14.3, 3p21.31, and 13q22.1) of which were novel. All of the 47 susceptibility loci conjointly accounted for 44.12% of the NSOFC heritability in the Chinese Han population. Our results improve the comprehending of genetic susceptibility to NSOFCs and provide new views into the genetic etiology of craniofacial deformities.