case-parent trios ; nicotinic cholinergic receptor genes

Objective: Multiple studies have suggested nonsyndromic cleft lip with or without cleft palate (NSCL/P) and lung cancer may have common genetic etiology. Previous studies have showed genetic variants in nicotinic cholinergic receptor genes (CHRNs) may influence risk of lung cancer. We aimed to explore the effect of CHRNs on risk of NSCL/P considering gene-gene (GxG) interaction for these genes. Subjects and Methods: We selected 120 markers in 14 CHRNs to test for GxG interaction using 806 Chinese case-parent trios recruited from an international consortium established for a GWAS of oral clefts. Results: Totally, two pairs of SNPs yielded significant GxG interactions after Bonferroni correction (rs935865 and rs2337980 with P=4.04×10, rs2741335 and rs3743077 with P=4.80×10), and these pairwise interactions were confirmed in permutation tests. In addition, the relative risk (RR) of the putative interaction between rs935865 and rs2337980 was 1.10 (95%CI: 0.92~1.31). Conclusions: While the single SNP association and the gene-environment interaction analysis of 14 CHRN genes yielded no signal, the current study did demonstrate the importance of considering potential GxG interaction for exploring etiology of NSCL/P. This study suggests an important role for particular combinations of SNPs in CHRN genes in influencing risk to NSCL/P, which needs further study.