Large-scale whole-genome sequencing of the Icelandic population

doi:10.1038/ng.3247

. 2015 May;47(5):435-44.

doi: 10.1038/ng.3247. Epub 2015 Mar 25.

Large-scale whole-genome sequencing of the Icelandic population

Daniel F Gudbjartsson¹, Hannes Helgason¹, Sigurjon A Gudjonsson², Florian Zink², Asmundur Oddson², Arnaldur Gylfason², Soren Besenbacher³, Gisli Magnusson², Bjarni V Halldorsson⁴, Eirikur Hjartarson², Gunnar Th Sigurdsson², Simon N Stacey², Michael L Frigge², Hilma Holm⁵, Jona Saemundsdottir², Hafdis Th Helgadottir², Hrefna Johannsdottir², Gunnlaugur Sigfusson⁶, Gudmundur Thorgeirsson⁷, Jon Th Sverrisson⁸, Solveig Gretarsdottir², G Bragi Walters², Thorunn Rafnar², Bjarni Thjodleifsson⁹, Einar S Bjornsson¹⁰, Sigurdur Olafsson¹⁰, Hildur Thorarinsdottir¹¹, Thora Steingrimsdottir¹², Thora S Gudmundsdottir¹³, Asgeir Theodors¹¹, Jon G Jonasson¹⁴, Asgeir Sigurdsson², Gyda Bjornsdottir², Jon J Jonsson¹⁵, Olafur Thorarensen¹⁶, Petur Ludvigsson¹⁶, Hakon Gudbjartsson¹, Gudmundur I Eyjolfsson¹⁷, Olof Sigurdardottir¹⁸, Isleifur Olafsson¹⁹, David O Arnar⁷, Olafur Th Magnusson², Augustine Kong¹, Gisli Masson², Unnur Thorsteinsdottir²⁰, Agnar Helgason²¹, Patrick Sulem², Kari Stefansson²⁰

Affiliations

¹ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
² deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
³ Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle, Aarhus, Denmark.
⁴ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Institute of Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland.
⁵ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland.
⁷ 1] Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁸ Department of Internal Medicine, Akureyri Hospital, Akureyri, Iceland.
⁹ Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland.
¹⁰ 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
¹¹ Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
¹² 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
¹³ Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
¹⁴ 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland. [3] Icelandic Cancer Registry, Reykjavik, Iceland.
¹⁵ 1] Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.
¹⁶ Department of Pediatrics, Section of Child Neurology, The Children's Hospital of Reykjavik, Landspitali University Hospital, Reykjavik, Iceland.
¹⁷ Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), Reykjavik, Iceland.
¹⁸ Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland.
¹⁹ Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
²⁰ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
²¹ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Department of Anthropology, University of Iceland, Reykjavik, Iceland.

PMID: 25807286
DOI: 10.1038/ng.3247

Large-scale whole-genome sequencing of the Icelandic population

Daniel F Gudbjartsson et al. Nat Genet. 2015 May.

. 2015 May;47(5):435-44.

doi: 10.1038/ng.3247. Epub 2015 Mar 25.

Authors

Affiliations

¹ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
² deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
³ Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle, Aarhus, Denmark.
⁴ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Institute of Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland.
⁵ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland.
⁷ 1] Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁸ Department of Internal Medicine, Akureyri Hospital, Akureyri, Iceland.
⁹ Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland.
¹⁰ 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
¹¹ Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
¹² 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
¹³ Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
¹⁴ 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland. [3] Icelandic Cancer Registry, Reykjavik, Iceland.
¹⁵ 1] Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.
¹⁶ Department of Pediatrics, Section of Child Neurology, The Children's Hospital of Reykjavik, Landspitali University Hospital, Reykjavik, Iceland.
¹⁷ Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), Reykjavik, Iceland.
¹⁸ Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland.
¹⁹ Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
²⁰ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
²¹ 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Department of Anthropology, University of Iceland, Reykjavik, Iceland.

PMID: 25807286
DOI: 10.1038/ng.3247

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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Comment in

Letters from Iceland.
[No authors listed] [No authors listed] Nat Genet. 2015 May;47(5):425. doi: 10.1038/ng.3277. Nat Genet. 2015. PMID: 25807281
Largest set of human genomes from a single population is sequenced.
Mayor S. Mayor S. BMJ. 2015 Mar 27;350:h1720. doi: 10.1136/bmj.h1720. BMJ. 2015. PMID: 25820286 No abstract available.

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Large-scale whole-genome sequencing of the Icelandic population

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Large-scale whole-genome sequencing of the Icelandic population

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