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Open Access Research article

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

Blake E Haas1, Steve Horvath12, Kirsi H Pietiläinen34, Rita M Cantor1, Elina Nikkola1, Daphna Weissglas-Volkov1, Aila Rissanen5, Mete Civelek6, Ivette Cruz-Bautista7, Laura Riba8, Johanna Kuusisto9, Jaakko Kaprio10115, Teresa Tusie-Luna8, Markku Laakso9, Carlos A Aguilar-Salinas7 and Päivi Pajukanta1*

Author Affiliations

1 Department of Human Genetics and David Geffen School of Medicine at UCLA, Gonda Center, Room 6335B, 695 Charles E. Young Drive South, Los Angeles, California, 90095-7088, USA

2 Department of Biostatistics, David Geffen School of Medicine at the University of California, Los Angeles, USA

3 Obesity Research Unit, Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, and University of Helsinki, Helsinki, Finland

4 Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland

5 Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland

6 Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, USA

7 Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Mexico City, Mexico

8 Molecular Biology and Genomic Medicine Unit, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico

9 Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland

10 Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland

11 Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland

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BMC Medical Genomics 2012, 5:61  doi:10.1186/1755-8794-5-61

Published: 6 December 2012

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.

Keywords:
Mexicans; Finns; RNA sequencing; Triglycerides; Adipose tissue; Weighted gene co-expression network analysis