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Common variants in DLG1 locus are associated with non‐syndromic cleft lip with or without cleft palate
Author(s) -
Mostowska A.,
Gaczkowska A.,
Żukowski K.,
Ludwig K.U.,
Hozyasz K.K.,
Wójcicki P.,
Mangold E.,
Böhmer A.C.,
HeilmannHeimbach S.,
Knapp M.,
Zadurska M.,
Biedziak B.,
Budner M.,
Lasota A.,
DakteraMicker A.,
Jagodziński P.P.
Publication year - 2018
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13141
Subject(s) - genetics , locus (genetics) , genome wide association study , biology , single nucleotide polymorphism , craniofacial , gene , candidate gene , snp , genotype
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 ( P trend = 9.70E−10 and P trend = 8.96E−09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome‐wide significance threshold ( P trend < 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.