Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft
Two large studies of case–parent trios ascertained through a proband with a non-syndromic orofacial cleft (OFC, which includes cleft lip and palate, cleft lip alone, or cleft palate alone) were used to test for possible gene–environment (G × E) interaction between genome-wide markers (both observed...
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Frontiers Media S.A.
2021-04-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.621018/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wanying Zhang Sowmya Venkataraghavan Jacqueline B. Hetmanski Elizabeth J. Leslie Mary L. Marazita Mary L. Marazita Eleanor Feingold Seth M. Weinberg Seth M. Weinberg Ingo Ruczinski Margaret A. Taub Alan F. Scott Debashree Ray Terri H. Beaty |
spellingShingle |
Wanying Zhang Sowmya Venkataraghavan Jacqueline B. Hetmanski Elizabeth J. Leslie Mary L. Marazita Mary L. Marazita Eleanor Feingold Seth M. Weinberg Seth M. Weinberg Ingo Ruczinski Margaret A. Taub Alan F. Scott Debashree Ray Terri H. Beaty Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft Frontiers in Cell and Developmental Biology orofacial clefts oral clefts gene-environment interaction case-parent trio design genome-wide association study maternal smoking |
author_facet |
Wanying Zhang Sowmya Venkataraghavan Jacqueline B. Hetmanski Elizabeth J. Leslie Mary L. Marazita Mary L. Marazita Eleanor Feingold Seth M. Weinberg Seth M. Weinberg Ingo Ruczinski Margaret A. Taub Alan F. Scott Debashree Ray Terri H. Beaty |
author_sort |
Wanying Zhang |
title |
Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft |
title_short |
Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft |
title_full |
Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft |
title_fullStr |
Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft |
title_full_unstemmed |
Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft |
title_sort |
detecting gene-environment interaction for maternal exposures using case-parent trios ascertained through a case with non-syndromic orofacial cleft |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-04-01 |
description |
Two large studies of case–parent trios ascertained through a proband with a non-syndromic orofacial cleft (OFC, which includes cleft lip and palate, cleft lip alone, or cleft palate alone) were used to test for possible gene–environment (G × E) interaction between genome-wide markers (both observed and imputed) and self-reported maternal exposure to smoking, alcohol consumption, and multivitamin supplementation during pregnancy. The parent studies were as follows: GENEVA, which included 1,939 case–parent trios recruited largely through treatment centers in Europe, the United States, and Asia, and 1,443 case–parent trios from the Pittsburgh Orofacial Cleft Study (POFC) also ascertained through a proband with an OFC including three major racial/ethnic groups (European, Asian, and Latin American). Exposure rates to these environmental risk factors (maternal smoking, alcohol consumption, and multivitamin supplementation) varied across studies and among racial/ethnic groups, creating substantial differences in power to detect G × E interaction, but the trio design should minimize spurious results due to population stratification. The GENEVA and POFC studies were analyzed separately, and a meta-analysis was conducted across both studies to test for G × E interaction using the 2 df test of gene and G × E interaction and the 1 df test for G × E interaction alone. The 2 df test confirmed effects for several recognized risk genes, suggesting modest G × E effects. This analysis did reveal suggestive evidence for G × Vitamin interaction for CASP9 on 1p36 located about 3 Mb from PAX7, a recognized risk gene. Several regions gave suggestive evidence of G × E interaction in the 1 df test. For example, for G × Smoking interaction, the 1 df test suggested markers in MUSK on 9q31.3 from meta-analysis. Markers near SLCO3A1 also showed suggestive evidence in the 1 df test for G × Alcohol interaction, and rs41117 near RETREG1 (a.k.a. FAM134B) also gave suggestive significance in the meta-analysis of the 1 df test for G × Vitamin interaction. While it remains quite difficult to obtain definitive evidence for G × E interaction in genome-wide studies, perhaps due to small effect sizes of individual genes combined with low exposure rates, this analysis of two large case–parent trio studies argues for considering possible G × E interaction in any comprehensive study of complex and heterogeneous disorders such as OFC. |
topic |
orofacial clefts oral clefts gene-environment interaction case-parent trio design genome-wide association study maternal smoking |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.621018/full |
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doaj-d2d845570c634b34a0d2c00920c5d2202021-04-16T05:09:54ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-04-01910.3389/fcell.2021.621018621018Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial CleftWanying Zhang0Sowmya Venkataraghavan1Jacqueline B. Hetmanski2Elizabeth J. Leslie3Mary L. Marazita4Mary L. Marazita5Eleanor Feingold6Seth M. Weinberg7Seth M. Weinberg8Ingo Ruczinski9Margaret A. Taub10Alan F. Scott11Debashree Ray12Terri H. Beaty13Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Human Genetics, School of Medicine, Emory University, Atlanta, GA, United StatesCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine and Clinical and Translational Science, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine and Clinical and Translational Science, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesTwo large studies of case–parent trios ascertained through a proband with a non-syndromic orofacial cleft (OFC, which includes cleft lip and palate, cleft lip alone, or cleft palate alone) were used to test for possible gene–environment (G × E) interaction between genome-wide markers (both observed and imputed) and self-reported maternal exposure to smoking, alcohol consumption, and multivitamin supplementation during pregnancy. The parent studies were as follows: GENEVA, which included 1,939 case–parent trios recruited largely through treatment centers in Europe, the United States, and Asia, and 1,443 case–parent trios from the Pittsburgh Orofacial Cleft Study (POFC) also ascertained through a proband with an OFC including three major racial/ethnic groups (European, Asian, and Latin American). Exposure rates to these environmental risk factors (maternal smoking, alcohol consumption, and multivitamin supplementation) varied across studies and among racial/ethnic groups, creating substantial differences in power to detect G × E interaction, but the trio design should minimize spurious results due to population stratification. The GENEVA and POFC studies were analyzed separately, and a meta-analysis was conducted across both studies to test for G × E interaction using the 2 df test of gene and G × E interaction and the 1 df test for G × E interaction alone. The 2 df test confirmed effects for several recognized risk genes, suggesting modest G × E effects. This analysis did reveal suggestive evidence for G × Vitamin interaction for CASP9 on 1p36 located about 3 Mb from PAX7, a recognized risk gene. Several regions gave suggestive evidence of G × E interaction in the 1 df test. For example, for G × Smoking interaction, the 1 df test suggested markers in MUSK on 9q31.3 from meta-analysis. Markers near SLCO3A1 also showed suggestive evidence in the 1 df test for G × Alcohol interaction, and rs41117 near RETREG1 (a.k.a. FAM134B) also gave suggestive significance in the meta-analysis of the 1 df test for G × Vitamin interaction. While it remains quite difficult to obtain definitive evidence for G × E interaction in genome-wide studies, perhaps due to small effect sizes of individual genes combined with low exposure rates, this analysis of two large case–parent trio studies argues for considering possible G × E interaction in any comprehensive study of complex and heterogeneous disorders such as OFC.https://www.frontiersin.org/articles/10.3389/fcell.2021.621018/fullorofacial cleftsoral cleftsgene-environment interactioncase-parent trio designgenome-wide association studymaternal smoking |