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Clin Genet. 2018 Apr;93(4):784-793. doi: 10.1111/cge.13141. Epub 2018 Feb 11.

Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate.

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Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
Department of Animal Genetics and Breeding, National Research Institute of Animal Production, Balice, Poland.
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Department of Pediatrics, Institute of Mother and Child, Warsaw, Poland.
Plastic Surgery Clinic of Medical University in Wroclaw, Wroclaw, Poland.
Department of Plastic Surgery in Specialist Medical Center in Polanica Zdroj, Polanica Zdroj, Poland.
Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
Department of Orthodontics, Medical University of Warsaw, Warsaw, Poland.
Department of Dental Surgery, Division of Facial Malformation, Poznan University of Medical Sciences, Poznan, Poland.
Eastern Poland Burn Treatment and Reconstructive Center, Leczna, Poland.
Department of Jaw Orthopedics, Medical University of Lublin, Lublin, Poland.


Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (Ptrend  = 9.70E-10 and Ptrend  = 8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (Ptrend  < 1.00E-05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft-susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.


3q29; DLG1; GWAS; nsCL/P; replication analysis

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