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
Publication date
2019/8/15
Journal
Nature
Volume
572
Issue
7769
Pages
323-328
Publisher
Nature Publishing Group UK
Description
Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the …
Total citations
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