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Intermediary quantitative traits—an alternative in the identification of disease genes in asthma?

Genes & Immunity volume 15, pages 1–7 (2014)Cite this article

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Abstract

Intermediary quantitative traits are a possible alternative for the identification of disease genes. This may be particularly relevant when diagnostic criteria are not very well defined as described for asthma. We analyzed serum samples from 944 individuals of 218 asthma families for 17 cytokines (eotaxin, GM-CSF, IFNγ, IL1B, IL1RA, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12(p40), IL-13, IL-17, IL-23, IL-33, TSLP and TNF-α) and determined the heritability. Linked chromosomal regions were identified by a genome-wide analysis using 334 autosomal microsatellite marker and association tested by further 550 SNP marker at genes implicated earlier with immune response. Heritability varied with TNF-α and IL-8 levels having the highest and TSLP having the lowest heritability. Linkage was significantly increased only for IL-12(p40) at D17S949. There were multiple significant single-nucleotide polymorphisms (SNP) associations (P<0.05) as found in the transmission disequilibrium test, whereas only a few replicated in parents or children only. These include SNPs in IL1RN that were associated with IL-33 and TSLP levels, and a SNP in NR3C2 that was associated with eotaxin, IL-13 and IFN-γ levels. Circulating level of serum cytokines exhibits genetic associations with asthma traits that are otherwise not detected using clinical diagnosis or when the clinical details are ambiguous.

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Acknowledgements

We thank BMBF, Deutsche Forschungsgemeinschaft and National Genome Network. MS and MW are funded by HMGU (Helmholtz Center Munich), and the EU Grant Europrevall. We also thank all the participating families for their help and the members of the clinical centers for their work.

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  1. Institute of Lung Biology and Health (iLBD), Comprehensive Pneumology Center (CPC), Helmholtz Zentrum München, Munich-Neuherberg, Germany

    M Sargurupremraj, K Pukelsheim, T Hofer & M Wjst

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Sargurupremraj, M., Pukelsheim, K., Hofer, T. et al. Intermediary quantitative traits—an alternative in the identification of disease genes in asthma?. Genes Immun 15, 1–7 (2014). https://doi.org/10.1038/gene.2013.53

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