Year: 2018
Type: preprint
Study design: Observational Study
Abstract: ABSTRACT As yet undiscovered rare variants are hypothesized to substantially influence an individual’s risk for common diseases and traits, but sequencing studies aiming to identify such variants have generally been underpowered. In isolated populations that have expanded rapidly after a population bottleneck, deleterious alleles that passed through the bottleneck may be maintained at much higher frequencies than in other populations. In an exome sequencing study of nearly 20,000 cohort participants from northern and eastern Finnish populations that exemplify this phenomenon, most novel trait-associated deleterious variants are seen only in Finland or display frequencies more than 20 times higher than in other European populations. These enriched alleles underlie 34 novel associations with 21 disease-related quantitative traits and demonstrate a geographical clustering equivalent to that of Mendelian disease mutations characteristic of the Finnish population. Sequencing studies in populations without this unique history would require hundreds of thousands to millions of participants for comparable power for these variants.
DOI: 10.1101/464255
Authors: Adam E Locke, Karyn Meltz Steinberg, Charleston WK Chiang, Susan K Service, Aki S Havulinna, Laurel Stell, Matti Pirinen, Haley J Abel, Colby C Chiang, Robert S Fulton, Anne U Jackson, Chul Joo Kang, Krishna L Kanchi, Daniel C Koboldt, David E Larson, Joanne Nelson, Thomas J Nicholas, Arto Pietilä, Vasily Ramensky, Debashree Ray, Laura J Scott, Heather M Stringham, Jagadish Vangipurapu, Ryan Welch, Pranav Yajnik, Xianyong Yin, Johan G Eriksson, Mika Ala-Korpela, Marjo-Riitta Järvelin, Minna Männikkö, Hannele Laivuori, FinnGen Project, Susan K Dutcher, Nathan O Stitziel, Richard K Wilson, Ira M Hall, Chiara Sabatti, Aarno Palotie, Veikko Salomaa, Markku Laakso, Samuli Ripatti, Michael Boehnke, Nelson B Freimer
Institutions: Washington University in St. Louis, University of Michigan, University of Southern California, University of California, Los Angeles, University of Helsinki, Finnish Institute for Health and Welfare, Institute for Molecular Medicine Finland, Stanford University, Helsinki Institute for Information Technology, Nationwide Children's Hospital, The Ohio State University, University of Utah, National Research Center for Preventive Medicine, Johns Hopkins University, University of Eastern Finland, Folkhälsans Forskningscentrum, Baker Heart and Diabetes Institute, The Alfred Hospital, University of Bristol, MRC Integrative Epidemiology Unit, Monash University, University of Oulu, Oulu University Hospital, MRC Centre for Environment and Health, Imperial College London, Brunel University of London, Helsinki University Hospital, Tampere University Hospital, University of Tampere, Broad Institute, Massachusetts General Hospital, Kuopio University Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2899680682