Adipose co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes.

Adipose co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes.
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DOI:
10.1186/1755-8794-5-61
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发表时间:
2012-12-06
影响因子:
2.7
通讯作者:
Pajukanta P
Pajukanta P
中科院分区:
医学3区
文献类型:
--
作者:
Haas BE;Horvath S;Pietiläinen KH;Cantor RM;Nikkola E;Weissglas-Volkov D;Rissanen A;Civelek M;Cruz-Bautista I;Riba L;Kuusisto J;Kaprio J;Tusie-Luna T;Laakso M;Aguilar-Salinas CA;Pajukanta P

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高血清甘油三酯(TG)水平是冠心病(CHD)的既定危险因素。脂肪以甘油三酯的形式储存在人体脂肪组织中。我们假设人类脂肪组织中的基因共表达网络可能与血清 TG 水平相关,并有助于揭示参与 TG 调节的新基因。使用加权基因共表达网络分析 (WGCNA) 中的 blockwiseModules R 函数,从两个芬兰和一个墨西哥研究样本构建基因共表达网络。使用 Fisher 精确检验计算三个研究样本中每个样本的 TG 相关网络之间的重叠。基因本体论用于确定每个 TG 相关网络中丰富的已知途径。我们测量了来自两个芬兰和一个墨西哥研究样本的脂肪样本中的基因表达。在每个研究样本中,我们观察到与血清 TG 水平显着相关的基因共表达网络。在芬兰人和墨西哥人中观察到的 TG 模块显着重叠并共享 34 个基因。 34 个基因中的 7 个(ARHGAP30、CCR1、CXCL16、FERMT3、HCST、RNASET2、SELPG)被确定为所有三个 TG 模块的关键枢纽基因。此外,34 个基因中的两个(ARHGAP9、LST1)位于先前的 TG GWAS 区域,表明它们是 GWAS 信号背后的区域候选基因。这项研究提出了一种新型脂肪基因共表达网络,其中 34 个基因与人群中的血清 TG 显着相关。
High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation. Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher’s Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network. We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals. This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.
DOI: 10.1016/s0140-6736(10)60545-4
发表时间: 2010-05-08
期刊: LANCET
影响因子: 168.9
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