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Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population
Body surface area (BSA) is an important trait used for many clinical purposes. People’s BSA may vary due to genetic background, race, and different lifestyle factors (such as walking, exercise, reading, smoking, transportation, etc.). GWAS of BSA was conducted on 5,324 subjects of four ethnic popula...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213052/ https://www.ncbi.nlm.nih.gov/pubmed/34143809 http://dx.doi.org/10.1371/journal.pone.0253167 |
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author | Khatun, Mita Monir, Md. Mamun Xu, Ting Xu, Haiming Zhu, Jun |
author_facet | Khatun, Mita Monir, Md. Mamun Xu, Ting Xu, Haiming Zhu, Jun |
author_sort | Khatun, Mita |
collection | PubMed |
description | Body surface area (BSA) is an important trait used for many clinical purposes. People’s BSA may vary due to genetic background, race, and different lifestyle factors (such as walking, exercise, reading, smoking, transportation, etc.). GWAS of BSA was conducted on 5,324 subjects of four ethnic populations of European-American, African-American, Hispanic-American, and Chinese-American from the Multi-Ethnic Study of Atherocloris (MESA) data using unconditional and conditional full genetic models. In this study, fifteen SNPs were identified (Experiment-wise P(EW) < 1×10(−5)) using unconditional full genetic model, of which thirteen SNPs had individual genetic effects and seven SNPs were involved in four pairs of epistasis interactions. Seven single SNPs and eight pairs of epistasis SNPs were additionally identified using exercise, smoking, and transportation cofactor-conditional models. By comparing association analysis results from unconditional and cofactor conditional models, we observed three different scenarios: (i) genetic effects of several SNPs did not affected by cofactors, e.g., additive effect of gene CREB5 (a≙ –0.013 for T/T and 0.013 for G/G, −Log(10) P(EW) = 8.240) did not change in the cofactor models; (ii) genetic effects of several SNPs affected by cofactors, e.g., the genetic additive effect (a≙ 0.012 for A/A and –0.012 for G/G, −Log(10) P(EW) = 7.185) of SNP of the gene GRIN2A was not significant in transportation cofactor model; and (iii) genetic effects of several SNPs suppressed by cofactors, e.g., additive (a≙ –0.018 for G/G and 0.018 for C/C, −Log(10) P(EW) = 19.737) and dominance (d≙ –0.038 for G/C, −Log(10) P(EW) = 27.734) effects of SNP of gene ERBB4 was identified using only transportation cofactor model. Gene ontology analysis showed that several genes are related to the metabolic pathway of calcium compounds, coronary artery disease, type-2 Diabetes, Alzheimer disease, childhood obesity, sleeping duration, Parkinson disease, and cancer. This study revealed that lifestyle cofactors could contribute, suppress, increase or decrease the genetic effects of BSA associated genes. |
format | Online Article Text |
id | pubmed-8213052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82130522021-06-29 Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population Khatun, Mita Monir, Md. Mamun Xu, Ting Xu, Haiming Zhu, Jun PLoS One Research Article Body surface area (BSA) is an important trait used for many clinical purposes. People’s BSA may vary due to genetic background, race, and different lifestyle factors (such as walking, exercise, reading, smoking, transportation, etc.). GWAS of BSA was conducted on 5,324 subjects of four ethnic populations of European-American, African-American, Hispanic-American, and Chinese-American from the Multi-Ethnic Study of Atherocloris (MESA) data using unconditional and conditional full genetic models. In this study, fifteen SNPs were identified (Experiment-wise P(EW) < 1×10(−5)) using unconditional full genetic model, of which thirteen SNPs had individual genetic effects and seven SNPs were involved in four pairs of epistasis interactions. Seven single SNPs and eight pairs of epistasis SNPs were additionally identified using exercise, smoking, and transportation cofactor-conditional models. By comparing association analysis results from unconditional and cofactor conditional models, we observed three different scenarios: (i) genetic effects of several SNPs did not affected by cofactors, e.g., additive effect of gene CREB5 (a≙ –0.013 for T/T and 0.013 for G/G, −Log(10) P(EW) = 8.240) did not change in the cofactor models; (ii) genetic effects of several SNPs affected by cofactors, e.g., the genetic additive effect (a≙ 0.012 for A/A and –0.012 for G/G, −Log(10) P(EW) = 7.185) of SNP of the gene GRIN2A was not significant in transportation cofactor model; and (iii) genetic effects of several SNPs suppressed by cofactors, e.g., additive (a≙ –0.018 for G/G and 0.018 for C/C, −Log(10) P(EW) = 19.737) and dominance (d≙ –0.038 for G/C, −Log(10) P(EW) = 27.734) effects of SNP of gene ERBB4 was identified using only transportation cofactor model. Gene ontology analysis showed that several genes are related to the metabolic pathway of calcium compounds, coronary artery disease, type-2 Diabetes, Alzheimer disease, childhood obesity, sleeping duration, Parkinson disease, and cancer. This study revealed that lifestyle cofactors could contribute, suppress, increase or decrease the genetic effects of BSA associated genes. Public Library of Science 2021-06-18 /pmc/articles/PMC8213052/ /pubmed/34143809 http://dx.doi.org/10.1371/journal.pone.0253167 Text en © 2021 Khatun et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Khatun, Mita Monir, Md. Mamun Xu, Ting Xu, Haiming Zhu, Jun Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population |
title | Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population |
title_full | Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population |
title_fullStr | Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population |
title_full_unstemmed | Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population |
title_short | Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population |
title_sort | genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in mesa population |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213052/ https://www.ncbi.nlm.nih.gov/pubmed/34143809 http://dx.doi.org/10.1371/journal.pone.0253167 |
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