Cargando…
Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes
Introduction: Animal studies suggested that NFKB1, IKBKB, and SOCS3 genes could be involved in the association between overnutrition and obesity. This study aims to investigate interactions involving these genes and macronutrient intakes affecting obesity-related phenotypes. Methods: We used a tradi...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409307/ https://www.ncbi.nlm.nih.gov/pubmed/30886629 http://dx.doi.org/10.3389/fgene.2019.00151 |
_version_ | 1783401935551856640 |
---|---|
author | Tessier, François Fontaine-Bisson, Bénédicte Lefebvre, Jean-François El-Sohemy, Ahmed Roy-Gagnon, Marie-Hélène |
author_facet | Tessier, François Fontaine-Bisson, Bénédicte Lefebvre, Jean-François El-Sohemy, Ahmed Roy-Gagnon, Marie-Hélène |
author_sort | Tessier, François |
collection | PubMed |
description | Introduction: Animal studies suggested that NFKB1, IKBKB, and SOCS3 genes could be involved in the association between overnutrition and obesity. This study aims to investigate interactions involving these genes and macronutrient intakes affecting obesity-related phenotypes. Methods: We used a traditional statistical method, logistic regression, and compared it to alternative statistical method, multifactor dimensionality reduction (MDR) and penalized logistic regression (PLR), to better detect genes/environment interactions in the Toronto Nutrigenomics and Health Study (n = 1639) using dichotomized body mass index (BMI) and waist circumference as obesity-related phenotypes. Exposure variables included genotype on 54 single nucleotide polymorphisms (NFKB1: 18, IKBKB: 9, SOCS3: 27), macronutrient (carbohydrates, protein, fat) and alcohol intakes and ethno-cultural background. Results: After correction for multiple testing, no interaction was found using logistic regression. MDR identified interactions between SOCS3 rs6501199 and rs4969172, and IKBKB rs3747811 affecting BMI in the Caucasian population; SOCS3 rs6501199 and NFKB1 rs1609798 affecting WC in the Caucasian population; and SOCS3 rs4436839 and IKBKB rs3747811 affecting WC in the South Asian population. PLR found a main effect of SOCS3 rs12944581 on BMI among the South Asian population. Conclusion: While MDR and PLR had discordant results, some models support results from previous studies. These results emphasize the need to use alternative statistical methods to investigate high-order interactions and suggest that variants in the nutrient-responsive hypothalamic IKKB/NF-kB signaling pathway may be involved in obesity pathogenesis. |
format | Online Article Text |
id | pubmed-6409307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64093072019-03-18 Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes Tessier, François Fontaine-Bisson, Bénédicte Lefebvre, Jean-François El-Sohemy, Ahmed Roy-Gagnon, Marie-Hélène Front Genet Genetics Introduction: Animal studies suggested that NFKB1, IKBKB, and SOCS3 genes could be involved in the association between overnutrition and obesity. This study aims to investigate interactions involving these genes and macronutrient intakes affecting obesity-related phenotypes. Methods: We used a traditional statistical method, logistic regression, and compared it to alternative statistical method, multifactor dimensionality reduction (MDR) and penalized logistic regression (PLR), to better detect genes/environment interactions in the Toronto Nutrigenomics and Health Study (n = 1639) using dichotomized body mass index (BMI) and waist circumference as obesity-related phenotypes. Exposure variables included genotype on 54 single nucleotide polymorphisms (NFKB1: 18, IKBKB: 9, SOCS3: 27), macronutrient (carbohydrates, protein, fat) and alcohol intakes and ethno-cultural background. Results: After correction for multiple testing, no interaction was found using logistic regression. MDR identified interactions between SOCS3 rs6501199 and rs4969172, and IKBKB rs3747811 affecting BMI in the Caucasian population; SOCS3 rs6501199 and NFKB1 rs1609798 affecting WC in the Caucasian population; and SOCS3 rs4436839 and IKBKB rs3747811 affecting WC in the South Asian population. PLR found a main effect of SOCS3 rs12944581 on BMI among the South Asian population. Conclusion: While MDR and PLR had discordant results, some models support results from previous studies. These results emphasize the need to use alternative statistical methods to investigate high-order interactions and suggest that variants in the nutrient-responsive hypothalamic IKKB/NF-kB signaling pathway may be involved in obesity pathogenesis. Frontiers Media S.A. 2019-03-04 /pmc/articles/PMC6409307/ /pubmed/30886629 http://dx.doi.org/10.3389/fgene.2019.00151 Text en Copyright © 2019 Tessier, Fontaine-Bisson, Lefebvre, El-Sohemy and Roy-Gagnon. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Tessier, François Fontaine-Bisson, Bénédicte Lefebvre, Jean-François El-Sohemy, Ahmed Roy-Gagnon, Marie-Hélène Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes |
title | Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes |
title_full | Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes |
title_fullStr | Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes |
title_full_unstemmed | Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes |
title_short | Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes |
title_sort | investigating gene–gene and gene–environment interactions in the association between overnutrition and obesity-related phenotypes |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409307/ https://www.ncbi.nlm.nih.gov/pubmed/30886629 http://dx.doi.org/10.3389/fgene.2019.00151 |
work_keys_str_mv | AT tessierfrancois investigatinggenegeneandgeneenvironmentinteractionsintheassociationbetweenovernutritionandobesityrelatedphenotypes AT fontainebissonbenedicte investigatinggenegeneandgeneenvironmentinteractionsintheassociationbetweenovernutritionandobesityrelatedphenotypes AT lefebvrejeanfrancois investigatinggenegeneandgeneenvironmentinteractionsintheassociationbetweenovernutritionandobesityrelatedphenotypes AT elsohemyahmed investigatinggenegeneandgeneenvironmentinteractionsintheassociationbetweenovernutritionandobesityrelatedphenotypes AT roygagnonmariehelene investigatinggenegeneandgeneenvironmentinteractionsintheassociationbetweenovernutritionandobesityrelatedphenotypes |