Evaluating the effect of nicotinic cholinergic receptor genes on the risk of nonsyndromic cleft lip with or without cleft palate

Mengying Wang; Dongjing Liu; Holger Schwender; Hong Wang; Ping Wang; Zhibo Zhou; Jing Li; Tao Wu; Hongping Zhu; Terri H. Beaty

doi:10.1111/odi.12879

Evaluating the effect of nicotinic cholinergic receptor genes on the risk of nonsyndromic cleft lip with or without cleft palate

Mengying Wang, Dongjing Liu, Holger Schwender, Hong Wang, Ping Wang, Zhibo Zhou, Jing Li, Tao Wu, Hongping Zhu, Terri H. Beaty

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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 × 10⁻⁵, rs2741335 and rs3743077 with p = 4.80 × 10⁻⁴), 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, this 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.

Original language	English (US)
Pages (from-to)	1068-1072
Number of pages	5
Journal	Oral Diseases
Volume	24
Issue number	6
DOIs	https://doi.org/10.1111/odi.12879
State	Published - Sep 2018

Keywords

case–parent trios
gene–gene interaction
genomewide association study
nicotinic cholinergic receptor genes
nonsyndromic cleft lip with or without cleft palate
nonsyndromic oral cleft

ASJC Scopus subject areas

Otorhinolaryngology
General Dentistry

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10.1111/odi.12879

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@article{d13e0e1f610b472fa1def7ea080182bf,

title = "Evaluating the effect of nicotinic cholinergic receptor genes on the risk of nonsyndromic cleft lip with or without cleft palate",

abstract = "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 × 10−5, rs2741335 and rs3743077 with p = 4.80 × 10−4), 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, this 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.",

keywords = "case–parent trios, gene–gene interaction, genomewide association study, nicotinic cholinergic receptor genes, nonsyndromic cleft lip with or without cleft palate, nonsyndromic oral cleft",

author = "Mengying Wang and Dongjing Liu and Holger Schwender and Hong Wang and Ping Wang and Zhibo Zhou and Jing Li and Tao Wu and Hongping Zhu and Beaty, {Terri H.}",

note = "Funding Information: We gratefully acknowledge all families for participating in this study, and sincerely thank the effort of the clinical, field, and laboratory staff for contributing to this work and the Smile Train Foundation for supporting data collection in China. The Consortium for GWAS gen-otyping and data analysis was supported by The National Institute for Dental and Craniofacial Research through U01-DE-018993; “International Consortium to Identify Genes &Interactions Controlling Oral Clefts,” 2007-2009. This study also received funding support from The National Natural Science Foundation of China (81102178, 81573225, PI: Tao Wu) and Beijing Natural Science Foundation of China (7172115, PI: Tao Wu). Funding Information: Smile Train Foundation; The National Institute for Dental and Craniofacial Research, Grant/Award Number: U01- DE-018993; International Consortium to Identify Genes &Interactions Controlling Oral Clefts, Grant/Award Number: 2007-2009; The National Natural Science Foundation of China, Grant/Award Number: 81102178 and 81573225; Beijing Natural Science Foundation of China, Grant/Award Number: 7172115 Publisher Copyright: {\textcopyright} 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved",

year = "2018",

month = sep,

doi = "10.1111/odi.12879",

language = "English (US)",

volume = "24",

pages = "1068--1072",

journal = "Oral Diseases",

issn = "1354-523X",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - Evaluating the effect of nicotinic cholinergic receptor genes on the risk of nonsyndromic cleft lip with or without cleft palate

AU - Wang, Mengying

AU - Liu, Dongjing

AU - Schwender, Holger

AU - Wang, Hong

AU - Wang, Ping

AU - Zhou, Zhibo

AU - Li, Jing

AU - Wu, Tao

AU - Zhu, Hongping

AU - Beaty, Terri H.

N1 - Funding Information: We gratefully acknowledge all families for participating in this study, and sincerely thank the effort of the clinical, field, and laboratory staff for contributing to this work and the Smile Train Foundation for supporting data collection in China. The Consortium for GWAS gen-otyping and data analysis was supported by The National Institute for Dental and Craniofacial Research through U01-DE-018993; “International Consortium to Identify Genes &Interactions Controlling Oral Clefts,” 2007-2009. This study also received funding support from The National Natural Science Foundation of China (81102178, 81573225, PI: Tao Wu) and Beijing Natural Science Foundation of China (7172115, PI: Tao Wu). Funding Information: Smile Train Foundation; The National Institute for Dental and Craniofacial Research, Grant/Award Number: U01- DE-018993; International Consortium to Identify Genes &Interactions Controlling Oral Clefts, Grant/Award Number: 2007-2009; The National Natural Science Foundation of China, Grant/Award Number: 81102178 and 81573225; Beijing Natural Science Foundation of China, Grant/Award Number: 7172115 Publisher Copyright: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved

PY - 2018/9

Y1 - 2018/9

N2 - 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 × 10−5, rs2741335 and rs3743077 with p = 4.80 × 10−4), 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, this 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.

AB - 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 × 10−5, rs2741335 and rs3743077 with p = 4.80 × 10−4), 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, this 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.

KW - case–parent trios

KW - gene–gene interaction

KW - genomewide association study

KW - nicotinic cholinergic receptor genes

KW - nonsyndromic cleft lip with or without cleft palate

KW - nonsyndromic oral cleft

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UR - http://www.scopus.com/inward/citedby.url?scp=85052109883&partnerID=8YFLogxK

U2 - 10.1111/odi.12879

DO - 10.1111/odi.12879

M3 - Article

C2 - 29688589

AN - SCOPUS:85052109883

SN - 1354-523X

VL - 24

SP - 1068

EP - 1072

JO - Oral Diseases

JF - Oral Diseases

IS - 6

ER -

Evaluating the effect of nicotinic cholinergic receptor genes on the risk of nonsyndromic cleft lip with or without cleft palate

Abstract

Keywords

ASJC Scopus subject areas

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