Exome sequencing of Finnish isolates enhances rare-variant association power

FinnGen Project

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)323-328
Number of pages6
JournalNature
Volume572
Issue number7769
DOIs
StatePublished - Aug 15 2019

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Exome
Alleles
Population
Population Characteristics
Finland
Cluster Analysis
History
Mutation

ASJC Scopus subject areas

  • General

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Exome sequencing of Finnish isolates enhances rare-variant association power. / FinnGen Project.

In: Nature, Vol. 572, No. 7769, 15.08.2019, p. 323-328.

Research output: Contribution to journalArticle

FinnGen Project. / Exome sequencing of Finnish isolates enhances rare-variant association power. In: Nature. 2019 ; Vol. 572, No. 7769. pp. 323-328.
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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.",
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