期刊
NATURE
卷 572, 期 7769, 页码 323-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-019-1457-z
关键词
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资金
- Academy of Finland Center of Excellence in Complex Disease Genetics [312062]
- Academy of Finland [285380, 321428]
- Finnish Foundation for Cardiovascular Research
- Sigrid Juselius Foundation
- University of Helsinki HiLIFE Fellow grant
- RFBR [18-04-00789 A]
- Senior Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia [APP1158958]
- University of Bristol
- UK Medical Research Council [MC_UU_12013/1]
- Victorian Government's Operational Infrastructure Support Program
- Kuopio University Hospital
- Biocentrum Helsinki
- [HG006695]
- [HL113315]
- [MH105578]
- [DK062370]
- [NS062691]
- [5U54HG003079]
- [5UM1HG008853-03]
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.
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