title: Large-scale whole-genome sequencing of the Icelandic population.
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.
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
authors: Daniel F
authors: DF
authors: Gudbjartsson
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
authors: Hannes
authors: H
authors: Helgason
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Sigurjon A
authors: SA
authors: Gudjonsson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Florian
authors: F
authors: Zink
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Asmundur
authors: A
authors: Oddson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Arnaldur
authors: A
authors: Gylfason
authors: Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle, Aarhus, Denmark.
authors: Soren
authors: 0000000314551738
authors: S
authors: Besenbacher
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Gisli
authors: G
authors: Magnusson
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Institute of Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland.
authors: Bjarni V
authors: BV
authors: Halldorsson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Eirikur
authors: E
authors: Hjartarson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Gunnar Th
authors: GT
authors: Sigurdsson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Simon N
authors: SN
authors: Stacey
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Michael L
authors: 000000032984535X
authors: ML
authors: Frigge
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
authors: Hilma
authors: H
authors: Holm
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Jona
authors: J
authors: Saemundsdottir
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Hafdis Th
authors: HT
authors: Helgadottir
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Hrefna
authors: H
authors: Johannsdottir
authors: Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland.
authors: Gunnlaugur
authors: G
authors: Sigfusson
authors: 1] Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors: Gudmundur
authors: G
authors: Thorgeirsson
authors: Department of Internal Medicine, Akureyri Hospital, Akureyri, Iceland.
authors: Jon Th
authors: JT
authors: Sverrisson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Solveig
authors: S
authors: Gretarsdottir
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: G Bragi
authors: GB
authors: Walters
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Thorunn
authors: T
authors: Rafnar
authors: Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland.
authors: Bjarni
authors: B
authors: Thjodleifsson
authors: 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
authors: Einar S
authors: ES
authors: Bjornsson
authors: 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
authors: Sigurdur
authors: S
authors: Olafsson
authors: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
authors: Hildur
authors: H
authors: Thorarinsdottir
authors: 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
authors: Thora
authors: T
authors: Steingrimsdottir
authors: Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
authors: Thora S
authors: TS
authors: Gudmundsdottir
authors: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
authors: Asgeir
authors: A
authors: Theodors
authors: 1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland. [3] Icelandic Cancer Registry, Reykjavik, Iceland.
authors: Jon G
authors: JG
authors: Jonasson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Asgeir
authors: A
authors: Sigurdsson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Gyda
authors: G
authors: Bjornsdottir
authors: 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.
authors: Jon J
authors: JJ
authors: Jonsson
authors: Department of Pediatrics, Section of Child Neurology, The Children's Hospital of Reykjavik, Landspitali University Hospital, Reykjavik, Iceland.
authors: Olafur
authors: O
authors: Thorarensen
authors: Department of Pediatrics, Section of Child Neurology, The Children's Hospital of Reykjavik, Landspitali University Hospital, Reykjavik, Iceland.
authors: Petur
authors: P
authors: Ludvigsson
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
authors: Hakon
authors: H
authors: Gudbjartsson
authors: Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), Reykjavik, Iceland.
authors: Gudmundur I
authors: GI
authors: Eyjolfsson
authors: Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland.
authors: Olof
authors: O
authors: Sigurdardottir
authors: Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
authors: Isleifur
authors: I
authors: Olafsson
authors: 1] Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors: David O
authors: DO
authors: Arnar
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Olafur Th
authors: OT
authors: Magnusson
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
authors: Augustine
authors: A
authors: Kong
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Gisli
authors: G
authors: Masson
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors: Unnur
authors: U
authors: Thorsteinsdottir
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Department of Anthropology, University of Iceland, Reykjavik, Iceland.
authors: Agnar
authors: A
authors: Helgason
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
authors: Patrick
authors: 0000000171236123
authors: P
authors: Sulem
authors: 1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors: Kari
authors: K
authors: Stefansson
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000235:genetics; D010244:Bulbar Palsy, Progressive / Q000235:genetics; D002864:Chromogranins; D005260:Female; D016368:Frameshift Mutation; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation; D007055:Iceland; D008107:Liver Diseases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D018994:Myosin Light Chains / Q000235:genetics*; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012306:Risk; D017422:Sequence Analysis, DNA; D013972:Thyrotropin / Q000097:blood
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D002864:Chromogranins; C000599129:MYL4 protein, human; D018994:Myosin Light Chains; D043562:Receptors, G-Protein-Coupled; C540350:SLC52A2 protein, human; D013972:Thyrotropin; C095122:multidrug resistance protein 3; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs