Evidence map›Paper›PMID 31367044›Full record

ArticleNature2019

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

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 and 33 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 128 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

128 citing papers in PubMed, 5 syntheses or guidelines pooled it.

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68 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors.

Adam E Locke *Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Karyn Meltz Steinberg *McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Charleston W K Chiang *Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
Susan K Service *Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
Aki S HavulinnaInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Laurel StellDepartment of Biomedical Data Science, Stanford University, Stanford, CA, USA.
Matti PirinenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Haley J AbelMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Colby C ChiangMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Robert S FultonMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Anne U JacksonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Chul Joo KangMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Krishna L KanchiMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Daniel C KoboldtMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
David E LarsonMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Joanne NelsonMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Thomas J NicholasMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Arto PietiläNational Institute for Health and Welfare, Helsinki, Finland.
Vasily RamenskyCenter for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
Debashree RayDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Laura J ScottDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Heather M StringhamDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Jagadish VangipurapuInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Ryan WelchDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Pranav YajnikDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Xianyong YinDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Johan G ErikssonDepartment of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
Mika Ala-KorpelaSystems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Marjo-Riitta JärvelinBiocenter Oulu, University of Oulu, Oulu, Finland.
Minna MännikköCenter for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
Hannele LaivuoriInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
FinnGen Project
Susan K DutcherMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Nathan O StitzielMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Richard K WilsonMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
Ira M HallDepartment of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Chiara SabattiDepartment of Biomedical Data Science, Stanford University, Stanford, CA, USA.
Aarno PalotieInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Veikko SalomaaNational Institute for Health and Welfare, Helsinki, Finland.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Samuli RipattiInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA. boehnke@umich.edu.
Nelson B FreimerCenter for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA. nfreimer@mednet.ucla.edu.

Funding

Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7M
Supplement Proposal: Accelerated Genome Aggregation and Joint Variant Calling EffortUM1HG008853 · NHGRI · WASHINGTON UNIVERSITY · PI HALL, IRA M, MILBRANDT, JEFFREY D · 2016 to 2020
$76.2M
Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Brian N Finck · 1999 to 2026
$30.2M
Identifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6M
1/2 Genomic Strategies to Identify High-impact Psychiatric Risk VariantsU01MH105578 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B., GESCHWIND, DANIEL H · 2014 to 2018
$8.5M
Integrative Center for Neurogenetics and Neurogenomics - OverallP30NS062691 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COPPOLA, GIOVANNI · 2009 to 2018
$7.4M
Identifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7M
Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
Genomic and Metabolomic Profiling of Finnish Familial Dyslipidemia FamiliesR01HL113315 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B., PALOTIE, AARNO · 2012 to 2016
$3.4M
ANGPTL3 DEFICIENCY AND ATHEROSCLEROSIS IN HUMANSR01HL131961 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2016 to 2020
$3.2M
New Statistical Methods for High Resolution Mapping of Multiple PhenotypesR01HG006695 · NHGRI · STANFORD UNIVERSITY · PI SABATTI, CHIARA · 2013 to 2015
$1.0M
Identifying Genes for Type 2 Diabetes: FUSIONR56DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L · 2008 to 2008
$500k
Medical Research Council MC_UU_12013/1Medical Research Council MR/S019669/1NHGRI NIH HHS R01 HG006695NHGRI NIH HHS U54 HG003079NHGRI NIH HHS UM1 HG008853NHLBI NIH HHS R01 HL113315NHLBI NIH HHS R01 HL131961NIDDK NIH HHS P30 DK056341NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R56 DK062370NIDDK NIH HHS U01 DK062370NIMH NIH HHS U01 MH105578NINDS NIH HHS P30 NS062691NINDS NIH HHS T32 NS048004
6 · The paper itself

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.

Indexed as

Exome SequencingAllelesCholesterol, HDLCluster AnalysisEndpoint DeterminationFinlandGenetic Association StudiesGenetic Predisposition to DiseaseGenetic VariationGeographic MappingHumansMultifactorial InheritanceQuantitative Trait LociReproducibility of ResultsCholesterol, HDL

Identifiers

PMID31367044
PMCPMC6697530

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.