Genetics of gene expression and its effect on disease (original) (raw)

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Gene Expression Omnibus

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All the gene expression data generated for this study have been deposited into the GEO database under accession numbers GSE7965 and GPL3991. The authors declare competing financial interests: details accompany the full-text HTML version of the paper at www.nature.com/nature.

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Acknowledgements

The authors acknowledge the participating families and the staff at the Clinical Research Centre for their cooperation. Genotyping service was provided at the deCode Genetics genotyping facilities.

Author Contributions V.E., E.E.S., K.S. and G.T. wrote the paper. G.T., E.E.S., A.K., D.G. and F.Z. performed statistical analysis. Tissue sampling and/or molecular profiling was carried out by H.G.G., T.S., B.G.L., G.H.E., S.C., M.M., Aslaug Jonasdottir, Adalbjorg Jonasdottir, G.B. and K.K. V.E., J.Z., U.T., A.S.L., A.H., B.Z., G.B.W., S. Gunnarsdottir, S. Gretarsdottir, K.P.M., V.S., I.R., A.H., U.S., H.S., R.F., J.R.G., K.S., M.L.R. and J.R.L. performed the genetic analysis and/or data-mining. K.S. and E.E.S. contributed equally to this work.

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Author notes

1. Eric E. Schadt and Kari Stefansson: These authors contributed equally to this work.

Authors and Affiliations

1. deCODE genetics, 101 Reykjavik, Iceland
   Valur Emilsson, Gudmar Thorleifsson, Florian Zink, Agnar Helgason, G. Bragi Walters, Steinunn Gunnarsdottir, Magali Mouy, Valgerdur Steinthorsdottir, Gudrun H. Eiriksdottir, Gyda Bjornsdottir, Inga Reynisdottir, Daniel Gudbjartsson, Anna Helgadottir, Aslaug Jonasdottir, Adalbjorg Jonasdottir, Unnur Styrkarsdottir, Solveig Gretarsdottir, Kristinn P. Magnusson, Hreinn Stefansson, Ragnheidur Fossdal, Kristleifur Kristjansson, Unnur Thorsteinsdottir, Jeffrey R. Gulcher, Augustine Kong & Kari Stefansson
2. Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, Washington 98109, USA,
   Valur Emilsson, Bin Zhang, Amy S. Leonardson, Jun Zhu, Sonia Carlson, John R. Lamb & Eric E. Schadt
3. Department of Surgery, National University Hospital, 101 Reykjavik, Iceland
   Hjortur G. Gislason, Tryggvi Stefansson & Bjorn G. Leifsson
4. Merck Research Laboratories, Rahway, New Jersey 07065, USA,
   Marc L. Reitman

Authors

1. Valur Emilsson
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2. Gudmar Thorleifsson
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3. Bin Zhang
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4. Amy S. Leonardson
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5. Florian Zink
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6. Jun Zhu
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7. Sonia Carlson
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8. Agnar Helgason
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9. G. Bragi Walters
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10. Steinunn Gunnarsdottir
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11. Magali Mouy
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12. Valgerdur Steinthorsdottir
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13. Gudrun H. Eiriksdottir
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14. Gyda Bjornsdottir
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15. Inga Reynisdottir
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16. Daniel Gudbjartsson
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17. Anna Helgadottir
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18. Aslaug Jonasdottir
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19. Adalbjorg Jonasdottir
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20. Unnur Styrkarsdottir
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21. Solveig Gretarsdottir
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22. Kristinn P. Magnusson
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23. Hreinn Stefansson
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24. Ragnheidur Fossdal
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25. Kristleifur Kristjansson
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26. Hjortur G. Gislason
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27. Tryggvi Stefansson
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28. Bjorn G. Leifsson
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29. Unnur Thorsteinsdottir
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30. John R. Lamb
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31. Jeffrey R. Gulcher
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32. Marc L. Reitman
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33. Augustine Kong
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34. Eric E. Schadt
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35. Kari Stefansson
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Corresponding authors

Correspondence toEric E. Schadt or Kari Stefansson.

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Competing interests

The following authors own stocks in either deCode Genetics, Inc. or Merck & Co., Inc.: V.E., E.E.S., G.T., G.B., S.C., M.M., J.Z., Aslaug Jonasdottir, Adalbjorg Jonasdottir, K.K., U.T., A.S.L., A.H., B.Z., G.B.W., F.Z., S. Gunnarsdottir, S. Gretarsdottir, K.P.M., V.S., I.R., D.G., A.H., U.S. H.S., R.F., A.K., K.S., J.R.G., M.L.R. and J.R.L.

Supplementary information

Supplementary Information

The file contains Supplementary Results with additional references, Supplementary Tables 1-7 and Supplementary Figures 1-7 with Legends. The file contains Supplementary Results on the probes overlapping SNPs, distribution of cis eSNPs as regards the location of probes, detection of trans eQTLs and eQTL hotspots, comparison of expression linkage and association results and finally the additional information regarding genes in the mouse MEMN that have been shown to be causal for metabolic diseases. Tables include a summary of cohort description (Supplementary Table 1), results on the re-sequencing of array probes (Supplementary Table 2), expression trait vs. clinical trait correlations (Supplementary Table 3), heritability and eQTL results (Supplementary Tables 4 and 5), detection of significant trans eQTLs and eQTL hotspots (Supplementary Table 6) and finally the pathway enrichment for the gene sets in the MEMN module (Supplementary Table 7). The figures show chromosomal distribution of eQTLs in IFB in the real data and a simulated dataset (Supplementary Figure 1), distribution of BMI, gene expression vs. BMI correlations and heritability in the IFA cohort (Supplementary Figure 2), the agreement between the linkage and association data (Supplementary Figure 3), distribution of cis eSNPs as regards the location of probes (Supplementary Figure 4), the localization and specificity of the association signal (Supplementary Figure 5), the gene set overlap between the male and female specific MEMN module in humans (Supplementary Figure 6) and finally the comparison between the connectivity structure of the MEMN genes in between the females and males. (PDF 828 kb)

Supplementary description

The file contains description of the RNA sample processing, the design of the arrays, quality controlling and processing of the probe hybridization. Here, appropriate references and Figure 1 (as an example of the data display) are provided as well. (PDF 179 kb)

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Emilsson, V., Thorleifsson, G., Zhang, B. et al. Genetics of gene expression and its effect on disease.Nature 452, 423–428 (2008). https://doi.org/10.1038/nature06758

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• Received: 23 July 2007
• Accepted: 28 January 2008
• Published: 16 March 2008
• Issue Date: 27 March 2008
• DOI: https://doi.org/10.1038/nature06758