Author
Listed:
- Adam E. Locke
(Washington University School of Medicine
Washington University School of Medicine
University of Michigan School of Public Health)
- Karyn Meltz Steinberg
(Washington University School of Medicine
Washington University School of Medicine)
- Charleston W. K. Chiang
(University of California Los Angeles
University of Southern California
University of Southern California)
- Susan K. Service
(University of California Los Angeles)
- Aki S. Havulinna
(University of Helsinki
National Institute for Health and Welfare)
- Laurel Stell
(Stanford University)
- Matti Pirinen
(University of Helsinki
University of Helsinki
University of Helsinki)
- Haley J. Abel
(Washington University School of Medicine
Washington University School of Medicine)
- Colby C. Chiang
(Washington University School of Medicine)
- Robert S. Fulton
(Washington University School of Medicine
Washington University School of Medicine)
- Anne U. Jackson
(University of Michigan School of Public Health)
- Chul Joo Kang
(Washington University School of Medicine)
- Krishna L. Kanchi
(Washington University School of Medicine)
- Daniel C. Koboldt
(Washington University School of Medicine
Nationwide Children’s Hospital
The Ohio State University College of Medicine)
- David E. Larson
(Washington University School of Medicine
Washington University School of Medicine)
- Joanne Nelson
(Washington University School of Medicine)
- Thomas J. Nicholas
(Washington University School of Medicine
University of Utah)
- Arto Pietilä
(National Institute for Health and Welfare)
- Vasily Ramensky
(University of California Los Angeles
Federal State Institution “National Medical Research Center for Preventive Medicine” of the Ministry of Healthcare of the Russian Federation)
- Debashree Ray
(University of Michigan School of Public Health
Johns Hopkins University)
- Laura J. Scott
(University of Michigan School of Public Health)
- Heather M. Stringham
(University of Michigan School of Public Health)
- Jagadish Vangipurapu
(University of Eastern Finland)
- Ryan Welch
(University of Michigan School of Public Health)
- Pranav Yajnik
(University of Michigan School of Public Health)
- Xianyong Yin
(University of Michigan School of Public Health)
- Johan G. Eriksson
(National Institute for Health and Welfare
Folkhälsan Research Center
University of Helsinki, Helsinki and Helsinki University Hospital)
- Mika Ala-Korpela
(Baker Heart and Diabetes Institute
University of Oulu and Biocenter Oulu, University of Oulu
University of Eastern Finland
University of Bristol)
- Marjo-Riitta Järvelin
(University of Oulu
University of Oulu
Oulu University Hospital
Imperial College London)
- Minna Männikkö
(University of Oulu
University of Oulu)
- Hannele Laivuori
(University of Helsinki
University of Helsinki and Helsinki University Hospital
Tampere University Hospital and University of Tampere, Faculty of Medicine and Health Technology)
- Susan K. Dutcher
(Washington University School of Medicine
Washington University School of Medicine)
- Nathan O. Stitziel
(Washington University School of Medicine
Washington University School of Medicine)
- Richard K. Wilson
(Washington University School of Medicine
Nationwide Children’s Hospital
The Ohio State University College of Medicine)
- Ira M. Hall
(Washington University School of Medicine
Washington University School of Medicine)
- Chiara Sabatti
(Stanford University
Stanford University)
- Aarno Palotie
(University of Helsinki
Massachusetts General Hospital
Broad Institute of MIT and Harvard)
- Veikko Salomaa
(National Institute for Health and Welfare)
- Markku Laakso
(University of Eastern Finland
Kuopio University Hospital)
- Samuli Ripatti
(University of Helsinki
University of Helsinki
Broad Institute of MIT and Harvard)
- Michael Boehnke
(University of Michigan School of Public Health)
- Nelson B. Freimer
(University of California Los Angeles)
Abstract
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 Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power.
Suggested Citation
Adam E. Locke & Karyn Meltz Steinberg & Charleston W. K. Chiang & Susan K. Service & Aki S. Havulinna & Laurel Stell & Matti Pirinen & Haley J. Abel & Colby C. Chiang & Robert S. Fulton & Anne U. Jack, 2019.
"Exome sequencing of Finnish isolates enhances rare-variant association power,"
Nature, Nature, vol. 572(7769), pages 323-328, August.
Handle:
RePEc:nat:nature:v:572:y:2019:i:7769:d:10.1038_s41586-019-1457-z
DOI: 10.1038/s41586-019-1457-z
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Citations
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Cited by:
- Magdalena Zimoń & Yunfeng Huang & Anthi Trasta & Aliaksandr Halavatyi & Jimmy Z. Liu & Chia-Yen Chen & Peter Blattmann & Bernd Klaus & Christopher D. Whelan & David Sexton & Sally John & Wolfgang Hube, 2021.
"Pairwise effects between lipid GWAS genes modulate lipid plasma levels and cellular uptake,"
Nature Communications, Nature, vol. 12(1), pages 1-16, December.
- David R. Blair & Thomas J. Hoffmann & Joseph T. Shieh, 2022.
"Common genetic variation associated with Mendelian disease severity revealed through cryptic phenotype analysis,"
Nature Communications, Nature, vol. 13(1), pages 1-15, December.
- Xianyong Yin & Lap Sum Chan & Debraj Bose & Anne U. Jackson & Peter VandeHaar & Adam E. Locke & Christian Fuchsberger & Heather M. Stringham & Ryan Welch & Ketian Yu & Lilian Fernandes Silva & Susan K, 2022.
"Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci,"
Nature Communications, Nature, vol. 13(1), pages 1-14, December.
- Zichen Zhang & Ye Eun Bae & Jonathan R. Bradley & Lang Wu & Chong Wu, 2022.
"SUMMIT: An integrative approach for better transcriptomic data imputation improves causal gene identification,"
Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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