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

BackgroundNonsyndromic orofacial clefts (NSOFCs) are the most 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 of the observed NSOFCs heritability. MethodsHere, we performed GWASs of 1615 NSCPO cases and 2340 controls, and then conducted genome-wide meta-analyses of NSOFCs, totaling 6812 NSCL/P cases, 2614 NSCPO cases, and 19,165 controls from the Chinese Han population. ResultsWe identify 47 risk loci with genome-wide p(meta)-value <5.0 x 10(-8), 5 risk loci (1p32.1, 3p14.1, 3p14.3, 3p21.31, and 13q22.1) of which are new. All of the 47 susceptibility loci conjointly account for 44.12% of the NSOFCs' heritability in the Chinese Han population. ConclusionOur results improve the comprehending of genetic susceptibility to NSOFCs and provide new views into the genetic etiology of craniofacial anomalies.

Automated summary

In this study, genome-wide association studies and meta-analyses were conducted on a Chinese Han population to identify risk loci for nonsyndromic orofacial clefts. A total of 47 risk loci were identified, including 5 new loci, which collectively accounted for 44.12% of the heritability of orofacial clefts in the population.