| Title | Gene-gene interaction of single nucleotide polymorphisms in 16p13.3 may contribute to the risk of non-syndromic cleft lip with or without cleft palate in Chinese case-parent trios |
| Authors | Liu, Dongjing Wang, Hong Schwender, Holger Marazita, Mary L. Wang, Zhuqing Yuan, Yuan Wang, Ping Liang, Kung Yee Wu-Chou, Yah Huei Wang, Mengying Shi, Bing Zhu, Hongping Wu, Tao Beaty, Terri H. |
| Affiliation | Peking Univ, Sch Publ Hlth, Beijing, Peoples R China. Heinrich Heine Univ Duesseldorf, Math Inst, Dusseldorf, Germany. Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. Beijing Ctr Dis Prevent & Control, Beijing, Peoples R China. Natl Yang Ming Univ, Taipei, Taiwan. Chang Gung Mem Hosp, Taoyuan, Taiwan. Sichuan Univ, West China Coll Stomatol, State Key Lab Oral Dis, Chengdu, Peoples R China. Peking Univ, Sch Stomatol, Beijing, Peoples R China. Minist Hlth, Key Lab Reprod Hlth, Beijing, Peoples R China. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Peking Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 38 Xue Yuan Rd, Beijing, Peoples R China. |
| Keywords | case-parent trios gene-gene interaction genome-wide association study non-syndromic cleft lip with or without cleft palate GENOME-WIDE ASSOCIATION RUBINSTEIN-TAYBI-SYNDROME LONG-RANGE ENHANCERS ENVIRONMENT INTERACTION NONCODING RNAS SUSCEPTIBILITY LOCUS VARIANTS DISEASE DETECT 8Q24 |
| Issue Date | 2017 |
| Publisher | AMERICAN JOURNAL OF MEDICAL GENETICS PART A |
| Citation | AMERICAN JOURNAL OF MEDICAL GENETICS PART A.2017,173(6),1489-1494. |
| Abstract | Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with a complex and heterogeneous etiology. A recent genome-wide association study (GWAS) among Chinese populations has identified a new region at 16p13.3 as being associated with NSCL/P, which requires further replication. Here, we attempted to replicate and further clarify the genetic association between this region and NSCL/P, as well as testing for potential gene-gene (G x G) and gene-environment (G x E) interactions. We conducted transmission disequilibrium tests on 69 single nucleotide polymorphisms (SNPs) mapping to 16p13.3 among 806 Chinese case-parent trios ascertained through an international consortium where a GWAS of oral clefts was conducted. G x G, as well as G x E interactions involving maternal environmental tobacco smoke (ETS) and multivitamin supplementation, were explored using conditional logistic regression model. We applied Cordell's method as implemented in the R package TRIO to test for possible interactions. While no SNPs showed evidence of linkage and association with NSCL/P after Bonferroni correction, we found signals of G x G interactions between SNPs in 16p13.3. Nine pairs of SNP-SNP interactions attained significance after Bonferroni correction, among which the most significant interaction was found between rs2072346 (ADCY9) and rs11646137 (intergenic region, P = 7.2 x 10(-5)). Linkage disequilibrium (LD) analysis revealed only low level of LD between these SNPs. This study failed to confirm the significant association between SNPs within 16p13.3 and the risk of NSCL/P, but underlined the importance of taking into account potential G x G interactions for the genetic association analysis of NSCL/P. |
| URI | http://hdl.handle.net/20.500.11897/472974 |
| ISSN | 1552-4825 |
| DOI | 10.1002/ajmg.a.38190 |
| Indexed | SCI(E) |
| Appears in Collections: | 公共卫生学院 口腔医院 |
