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 p...

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Autores principales:	Mita Khatun, Md Mamun Monir, Ting Xu, Haiming Xu, Jun Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/49646b544812409bb5d72af9cc146c5a
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spelling	oai:doaj.org-article:49646b544812409bb5d72af9cc146c5a2021-12-02T20:10:24ZGenome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population.1932-620310.1371/journal.pone.0253167https://doaj.org/article/49646b544812409bb5d72af9cc146c5a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253167https://doaj.org/toc/1932-6203Body 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 PEW < 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, -Log10 PEW = 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, -Log10 PEW = 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, -Log10 PEW = 19.737) and dominance (d≙ -0.038 for G/C, -Log10 PEW = 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.Mita KhatunMd Mamun MonirTing XuHaiming XuJun ZhuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253167 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mita Khatun Md Mamun Monir Ting Xu Haiming Xu Jun Zhu Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population.
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 PEW < 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, -Log10 PEW = 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, -Log10 PEW = 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, -Log10 PEW = 19.737) and dominance (d≙ -0.038 for G/C, -Log10 PEW = 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	article
author	Mita Khatun Md Mamun Monir Ting Xu Haiming Xu Jun Zhu
author_facet	Mita Khatun Md Mamun Monir Ting Xu Haiming Xu Jun Zhu
author_sort	Mita Khatun
title	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_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_sort	genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in mesa population.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/49646b544812409bb5d72af9cc146c5a
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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.

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