title: Whole-genome view of the consequences of a population bottleneck using 2926 genome sequences from Finland and United Kingdom.
abstract: Isolated populations with enrichment of variants due to recent population bottlenecks provide a powerful resource for identifying disease-associated genetic variants and genes. As a model of an isolate population, we sequenced the genomes of 1463 Finnish individuals as part of the Sequencing Initiative Suomi (SISu) Project. We compared the genomic profiles of the 1463 Finns to a sample of 1463 British individuals that were sequenced in parallel as part of the UK10K Project. Whereas there were no major differences in the allele frequency of common variants, a significant depletion of variants in the rare frequency spectrum was observed in Finns when comparing the two populations. On the other hand, we observed >2.1 million variants that were twice as frequent among Finns compared with Britons and 800 000 variants that were more than 10 times more frequent in Finns. Furthermore, in Finns we observed a relative proportional enrichment of variants in the minor allele frequency range between 2 and 5% (P<2.2 × 10-16). When stratified by their functional annotations, loss-of-function variants showed the highest proportional enrichment in Finns (P=0.0291). In the non-coding part of the genome, variants in conserved regions (P=0.002) and promoters (P=0.01) were also significantly enriched in the Finnish samples. These functional categories represent the highest a priori power for downstream association studies of rare variants using population isolates.
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Chheda
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.|Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Priit
authors.identifier: 0000-0001-9320-7008
authors.initials: P
authors.lastname: Palta
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Pirinen
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Shane
authors.identifier: 0000-0002-2715-4187
authors.initials: S
authors.lastname: McCarthy
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Klaudia
authors.identifier: 0000-0003-4448-0301
authors.initials: K
authors.lastname: Walter
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Koskinen
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.|Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Daly
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Richard
authors.identifier: 0000-0002-9130-1006
authors.initials: R
authors.lastname: Durbin
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.|Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.|Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.|Department of Mathematics and Statistics, University of Turku, Turku, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Aittokallio
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.|Public Health, Clinicum, University of Helsinki, Helsinki, Finland.
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
mesh_terms: D017124:Conserved Sequence; D005387:Finland; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000592:standards*; D006801:Humans; D059645:Mutation Rate; D011110:Polymorphism, Genetic; D011153:Population / Q000235:genetics*; D006113:United Kingdom