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Abstract

Here we describe the insights gained from sequencing the whole genomes of 2,636 Icelanders to a median depth of 20×. We found 20 million SNPs and 1.5 million insertions-deletions (indels). We describe the density and frequency spectra of sequence variants in relation to their functional annotation, gene position, pathway and conservation score. We demonstrate an excess of homozygosity and rare protein-coding variants in Iceland. We imputed these variants into 104,220 individuals down to a minor allele frequency of 0.1% and found a recessive frameshift mutation in MYL4 that causes early-onset atrial fibrillation, several mutations in ABCB4 that increase risk of liver diseases and an intronic variant in GNAS associating with increased thyroid-stimulating hormone levels when maternally inherited. These data provide a study design that can be used to determine how variation in the sequence of the human genome gives rise to human diversity.

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Acknowledgements

We thank all the participants in this study. This study was performed in collaboration with Illumina.

Author information

Author notes

    • Daniel F Gudbjartsson
    •  & Hannes Helgason

    These authors contributed equally to this work.

Affiliations

  1. deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.

    • Daniel F Gudbjartsson
    • , Hannes Helgason
    • , Sigurjon A Gudjonsson
    • , Florian Zink
    • , Asmundur Oddson
    • , Arnaldur Gylfason
    • , Gisli Magnusson
    • , Bjarni V Halldorsson
    • , Eirikur Hjartarson
    • , Gunnar Th Sigurdsson
    • , Simon N Stacey
    • , Michael L Frigge
    • , Hilma Holm
    • , Jona Saemundsdottir
    • , Hafdis Th Helgadottir
    • , Hrefna Johannsdottir
    • , Solveig Gretarsdottir
    • , G Bragi Walters
    • , Thorunn Rafnar
    • , Asgeir Sigurdsson
    • , Gyda Bjornsdottir
    • , Hakon Gudbjartsson
    • , Olafur Th Magnusson
    • , Augustine Kong
    • , Gisli Masson
    • , Unnur Thorsteinsdottir
    • , Agnar Helgason
    • , Patrick Sulem
    •  & Kari Stefansson
  2. School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.

    • Daniel F Gudbjartsson
    • , Hannes Helgason
    • , Hakon Gudbjartsson
    •  & Augustine Kong
  3. Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle, Aarhus, Denmark.

    • Soren Besenbacher
  4. Institute of Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland.

    • Bjarni V Halldorsson
  5. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.

    • Hilma Holm
  6. Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland.

    • Gunnlaugur Sigfusson
  7. Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland.

    • Gudmundur Thorgeirsson
    • , Bjarni Thjodleifsson
    •  & David O Arnar
  8. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Gudmundur Thorgeirsson
    • , Einar S Bjornsson
    • , Sigurdur Olafsson
    • , Thora Steingrimsdottir
    • , Jon G Jonasson
    • , David O Arnar
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  9. Department of Internal Medicine, Akureyri Hospital, Akureyri, Iceland.

    • Jon Th Sverrisson
  10. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.

    • Einar S Bjornsson
    • , Sigurdur Olafsson
    • , Hildur Thorarinsdottir
    •  & Asgeir Theodors
  11. Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.

    • Thora Steingrimsdottir
    •  & Thora S Gudmundsdottir
  12. Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.

    • Jon G Jonasson
  13. Icelandic Cancer Registry, Reykjavik, Iceland.

    • Jon G Jonasson
  14. Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Jon J Jonsson
  15. Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.

    • Jon J Jonsson
  16. Department of Pediatrics, Section of Child Neurology, The Children's Hospital of Reykjavik, Landspitali University Hospital, Reykjavik, Iceland.

    • Olafur Thorarensen
    •  & Petur Ludvigsson
  17. Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), Reykjavik, Iceland.

    • Gudmundur I Eyjolfsson
  18. Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland.

    • Olof Sigurdardottir
  19. Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.

    • Isleifur Olafsson
  20. Department of Anthropology, University of Iceland, Reykjavik, Iceland.

    • Agnar Helgason

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Contributions

D.F.G., H. Helgason, S.A.G., F.Z., D.O.A., O.T.M., G. Masson, A.H., P.S. and K.S. wrote the initial draft of the manuscript. D.F.G., H. Helgason, S.A.G., F.Z., A.O., G. Magnusson, B.V.H., E.H., G.T.S., S.N.S., M.L.F., A.K., G. Masson and P.S. analyzed the data. D.F.G., H. Helgason, S.A.G., F.Z., A.G., S.B., H.G. and G. Masson created methods for analyzing the data. S.N.S., H. Holm, J.S., H.T.H., H.J. and O.T.M. performed the experiments. H. Holm, G.S., G.T., J.T.S., S.G., G.B.W., T.R., B.T., E.S.B., S.O., H.T., T.S., T.S.G., A.T., J.G.J., A.S., G.B., J.J.J., O.T., P.L., G.I.E., O.S., I.O. and D.O.A. collected the samples and information. D.F.G., D.O.A., G. Masson, U.T., A.H., P.S. and K.S. designed the study.

Competing interests

The authors affiliated with deCODE Genetics are employed by the company, which is owned by Amgen, Inc: D.F.G., H. Helgason, S.A.G., F.Z., A.O., A.G., G. Magnusson, B.V.H., E.H., G.T.S., S.N.S., M.L.F., H. Holm, J.S., H.T.H., H.J., S.G., G.B.W., T.R., A.S., G.B., H.G., O.T.M., A.K., G. Masson, U.T., A.H., P.S. and K.S.

Corresponding authors

Correspondence to Daniel F Gudbjartsson or Kari Stefansson.

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https://doi.org/10.1038/ng.3247

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