Large-scale whole-genome sequencing of the Icelandic population.

• Published in: Nature Genetics
• Main Authors: Gudbjartsson, Daniel F, Helgason, Hannes, Gudjonsson, Sigurjon A, Zink, Florian, Oddson, Asmundur, Gylfason, Arnaldur, Besenbacher, Soren, Magnusson, Gisli, Halldorsson, Bjarni V, Hjartarson, Eirikur, Sigurdsson, Gunnar Th, Stacey, Simon N, Frigge, Michael L, Holm, Hilma, Saemundsdottir, Jona, Helgadottir, Hafdis Th, Johannsdottir, Hrefna, Sigfusson, Gunnlaugur, Thorgeirsson, Gudmundur, Sverrisson, Jon Th, Gretarsdottir, Solveig, Walters, G Bragi, Rafnar, Thorunn, Thjodleifsson, Bjarni, Bjornsson, Einar S, Olafsson, Sigurdur, Thorarinsdottir, Hildur, Steingrimsdottir, Thora, Gudmundsdottir, Thora S, Theodors, Asgeir, Jonasson, Jon G, Sigurdsson, Asgeir, Bjornsdottir, Gyda, Jonsson, Jon J, Thorarensen, Olafur, Ludvigsson, Petur, Gudbjartsson, Hakon, Eyjolfsson, Gudmundur I, Sigurdardottir, Olof, Olafsson, Isleifur, Arnar, David O, Magnusson, Olafur Th, Kong, Augustine, Masson, Gisli, Thorsteinsdottir, Unnur, Helgason, Agnar, Sulem, Patrick, Stefansson, Kari
• Other Authors: 1 Amgen Inc, DeCODE Genet, Reykjavik, Iceland 2 Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland 3 Aarhus Univ, Bioinformat Res Ctr, Aarhus, Denmark 4 Reykjavik Univ, Inst Biomed & Neural Engn, Reykjavik, Iceland 5 Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA 6 Landspitali Univ Hosp, Childrens Hosp, Reykjavik, Iceland 7 Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland 8 Univ Iceland, Fac Med, Reykjavik, Iceland 9 Akureyri Hosp, Dept Internal Med, Akureyri, Iceland 10 Landspitali Univ Hosp, Div Gastroenterol & Hepatol, Dept Internal Med, Reykjavik, Iceland 11 Landspitali Univ Hosp, Dept Obstet & Gynecol, Reykjavik, Iceland 12 Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland 13 Iceland Canc Registry, Reykjavik, Iceland 14 Univ Iceland, Dept Biochem & Mol Biol, Fac Med, Reykjavik, Iceland 15 Landspitali Univ Hosp, Dept Genet & Mol Med, Reykjavik, Iceland 16 Landspitali Univ Hosp, Childrens Hosp Reykjavik, Sect Child Neurol, Dept Pediat, Reykjavik, Iceland 17 Iceland Med Ctr Laeknasetrid, Lab Mjodd RAM, Reykjavik, Iceland 18 Akureyri Hosp, Dept Clin Biochem, Akureyri, Iceland 19 Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland 20 Univ Iceland, Dept Anthropol, Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group 2015
• Subjects: Aged; 80 and over; Atrial Fibrillation; Bulbar Palsy; Progressive; Female; Frameshift Mutation; GTP-Binding Protein alpha Subunits; Gs; Gene Frequency; Genetic Predisposition to Disease; Genome; Human; Genome-Wide Association Study; Hearing Loss; Sensorineural; Humans; INDEL Mutation; Iceland; Liver Diseases; Male; Middle Aged; Molecular Sequence Annotation; Myosin Light Chains; P-Glycoproteins; Phylogeography; Polymorphism; Single Nucleotide; Receptors; G-Protein-Coupled; Risk; Sequence Analysis; DNA; Thyrotropin; Indel’
• Online Access: http://hdl.handle.net/2336/560802; https://doi.org/10.1038/ng.3247

To access publisher's full text version of this article click on the hyperlink at the bottom of the page 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.