Investigation of dominant and recessive inheritance models in genome-wide association studies data of nonsyndromic cleft lip with or without cleft palate.

Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformation worldwide, and its etiology involves both genetic and environmental factors. Recent genome-wide and targeted genetic studies of nsCL/P have identified numerous genetic risk loci, under the hypothesis of a multiplicative mode of inheritance. The present study investigated whether novel nsCL/P risk loci could be identified by analyzing dominant/recessive genetic effects in single nucleotide polymorphism (SNP) data from genome-wide association studies. For this purpose, a genome-wide investigation of dominant/recessive common SNP effects was performed in our previously published meta-analysis data set. Twenty-four loci were identified as candidate regions. In a subsequent association analysis in an independent study cohort of 224 nsCL/P patients and 986 controls of European descent, none of the loci could be replicated. Therefore, our strategy of identifying novel loci by applying different genetic models did not yield any novel findings, suggesting that recessive/dominant common variation only make a limited contribution to nsCL/P in Europeans. However, we cannot rule out that such effects are present at some of the loci that have previously been identified, or are present in different populations.