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Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis

International Journal of Obesity volume 32, pages 816–825 (2008)Cite this article

Abstract

Context:

Obesity is a typical complex disorder resulting from behaviors promoted in westernized societies in the presence of a genetic predisposition. We hypothesized that new genes predisposing to obesity can be detected at the mRNA level.

Objective:

To identify susceptibility genes for obesity.

Design:

Linkage and expression profile data from different cohorts were combined to select novel candidate genes that were analyzed for association with obesity.

Setting and participants:

University Hospital in Stockholm. Adipose tissue mRNA levels were quantified in 96 women. Two large cohorts with a wide distribution in body mass index (BMI, n=1013 and 1423) were genotyped.

Main outcome measure:

mRNA levels and allelic association with obesity.

Results:

We confirmed association between candidate gene mRNA levels in adipose tissue and obesity. A total of 118 polymorphisms in 16 genes were analyzed for association with obesity. Single nucleotide polymorphism rs1064891, located in the 3′ UTR of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) gene, was nominally associated with obesity in combined analysis of cohorts 1 and 2 (P=0.007) and, in men that were lean or had severe obesity, with BMI (P=<0.005).

Conclusion:

To combine linkage and expression profile data is valuable in finding new obesity genes. PFKFB3, a potential regulator of glycolysis, displays decreased mRNA levels in adipose tissue of obese women, is associated with obesity and is a new promising candidate gene for obesity warranting further studies.

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Acknowledgements

This study was supported by grants from the AFA, Swedish Research Council, The Karolinska Institute, and the Foundations of Novo Nordic, Magnus Bergwall, Jeansson and Åke Wiberg. We thank Kerstin Wahlen, and Eva Sjolin for excellent technical assistance. We also thank the SNP technology platform at Uppsala University for the Illumina genotyping. The SNP technology platform at Uppsala University was supported with a grant from the K&A Wallenbergs Stiftelse to the Wallenberg Consortium North.

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Authors and Affiliations

  1. Department of Biosciences and Nutrition, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden

    H Jiao & J Kere

  2. Department of Medicine, Center for Metabolism and Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    M Kaaman, E Dungner, P Arner & I Dahlman

Authors
  1. H Jiao
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  2. M Kaaman
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Corresponding author

Correspondence to P Arner.

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Supplementary Information accompanies the paper on International Journal of Obesity website (http://www.nature.com/ijo)

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Jiao, H., Kaaman, M., Dungner, E. et al. Association analysis of positional obesity candidate genes based on integrated data from transcriptomics and linkage analysis. Int J Obes 32, 816–825 (2008). https://doi.org/10.1038/sj.ijo.0803789

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