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Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI

BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weight...

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Autores principales: Wang, Weijing, Jiang, Wenjie, Hou, Lin, Duan, Haiping, Wu, Yili, Xu, Chunsheng, Tan, Qihua, Li, Shuxia, Zhang, Dongfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683603/
https://www.ncbi.nlm.nih.gov/pubmed/29132311
http://dx.doi.org/10.1186/s12864-017-4257-6
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author Wang, Weijing
Jiang, Wenjie
Hou, Lin
Duan, Haiping
Wu, Yili
Xu, Chunsheng
Tan, Qihua
Li, Shuxia
Zhang, Dongfeng
author_facet Wang, Weijing
Jiang, Wenjie
Hou, Lin
Duan, Haiping
Wu, Yili
Xu, Chunsheng
Tan, Qihua
Li, Shuxia
Zhang, Dongfeng
author_sort Wang, Weijing
collection PubMed
description BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. RESULTS: In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly correlated with BMI (r = 0.56, P = 0.04), and hub genes of KCNN1 and AQP10 were differentially expressed. CONCLUSION: We identified significant genes and specific modules potentially related to BMI based on the gene expression profile data of monozygotic twins. The findings may help further elucidate the underlying mechanisms of obesity development and provide novel insights to research potential gene biomarkers and signaling pathways for obesity treatment. Further analysis and validation of the findings reported here are important and necessary when more sample size is acquired. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-017-4257-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-56836032017-11-27 Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI Wang, Weijing Jiang, Wenjie Hou, Lin Duan, Haiping Wu, Yili Xu, Chunsheng Tan, Qihua Li, Shuxia Zhang, Dongfeng BMC Genomics Research Article BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. RESULTS: In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly correlated with BMI (r = 0.56, P = 0.04), and hub genes of KCNN1 and AQP10 were differentially expressed. CONCLUSION: We identified significant genes and specific modules potentially related to BMI based on the gene expression profile data of monozygotic twins. The findings may help further elucidate the underlying mechanisms of obesity development and provide novel insights to research potential gene biomarkers and signaling pathways for obesity treatment. Further analysis and validation of the findings reported here are important and necessary when more sample size is acquired. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-017-4257-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-13 /pmc/articles/PMC5683603/ /pubmed/29132311 http://dx.doi.org/10.1186/s12864-017-4257-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Wang, Weijing
Jiang, Wenjie
Hou, Lin
Duan, Haiping
Wu, Yili
Xu, Chunsheng
Tan, Qihua
Li, Shuxia
Zhang, Dongfeng
Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI
title Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI
title_full Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI
title_fullStr Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI
title_full_unstemmed Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI
title_short Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI
title_sort weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to bmi
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683603/
https://www.ncbi.nlm.nih.gov/pubmed/29132311
http://dx.doi.org/10.1186/s12864-017-4257-6
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