Association of structural variation with cardiometabolic traits in Finns.

Alleles Cardiovascular Diseases / genetics Cholesterol / blood DNA Copy Number Variations / genetics Female Finland Genome, Human / genetics Genomic Structural Variation / genetics Genotype High-Throughput Nucleotide Sequencing Humans Male Mitochondrial Proteins / genetics Promoter Regions, Genetic / genetics Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / genetics Pyruvic Acid / metabolism Serum Albumin, Human / genetics
Finnish population cardiometabolic traits genome-wide association study structural variation

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
01 04 2021
Historique:
received: 12 12 2020
accepted: 03 03 2021
entrez: 2 4 2021
pubmed: 3 4 2021
medline: 8 5 2021
Statut: ppublish

Résumé

The contribution of genome structural variation (SV) to quantitative traits associated with cardiometabolic diseases remains largely unknown. Here, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. We used sensitive methods to identify and genotype 129,166 high-confidence SVs from deep whole-genome sequencing (WGS) data of 4,848 individuals. We tested the 64,572 common and low-frequency SVs for association with 116 quantitative traits and tested candidate associations using exome sequencing and array genotype data from an additional 15,205 individuals. We discovered 31 genome-wide significant associations at 15 loci, including 2 loci at which SVs have strong phenotypic effects: (1) a deletion of the ALB promoter that is greatly enriched in the Finnish population and causes decreased serum albumin level in carriers (p = 1.47 × 10

Identifiants

DOI: 10.1016/j.ajhg.2021.03.008 PMID: 33798444 PMC: PMC8059371
pubmed: 33798444
pii: S0002-9297(21)00092-6
doi: 10.1016/j.ajhg.2021.03.008
pmc: PMC8059371
pii:
doi:

Substances chimiques

ALB protein, human 0
Mitochondrial Proteins 0
PDPR protein, human 0
Pyruvic Acid 8558G7RUTR
Cholesterol 97C5T2UQ7J
Pyruvate Dehydrogenase (Lipoamide)-Phosphatase EC 3.1.3.43
Serum Albumin, Human ZIF514RVZR

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

583-596

Subventions

Organisme : NINDS NIH HHS
ID : T32 NS105604
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056341
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007081
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK062370
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008853
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062370
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG003079
Pays : United States

Informations de copyright

Copyright © 2021. Published by Elsevier Inc.

Références

Nat Genet. 2007 Nov;39(11):1361-8
pubmed: 17922013
Nat Commun. 2017 Sep 29;8(1):744
pubmed: 28963451
Genome Biol. 2014 Jun 26;15(6):R84
pubmed: 24970577
PLoS Genet. 2017 Oct 30;13(10):e1007079
pubmed: 29084231
Bioinformatics. 2003 Jan;19(1):149-50
pubmed: 12499305
Nat Genet. 2017 May;49(5):692-699
pubmed: 28369037
Science. 2004 Oct 22;306(5696):636-40
pubmed: 15499007
Mol Cell Endocrinol. 2014 Jan 25;382(1):740-757
pubmed: 22963884
Aust Fam Physician. 2017;46(7):456-459
pubmed: 28697287
Nature. 2010 Apr 1;464(7289):713-20
pubmed: 20360734
Nat Genet. 2009 Mar;41(3):334-41
pubmed: 19198609
Annu Rev Med. 2010;61:437-55
pubmed: 20059347
Nat Genet. 2016 Apr;48(4):359-66
pubmed: 26901066
J Hum Hypertens. 2019 Nov;33(11):775-785
pubmed: 31551569
Am J Hum Genet. 2017 Jul 6;101(1):5-22
pubmed: 28686856
Nat Genet. 2008 Oct;40(10):1166-74
pubmed: 18776908
Bioinformatics. 2019 Nov 1;35(22):4782-4787
pubmed: 31218349
Nat Commun. 2020 Jan 7;11(1):39
pubmed: 31911595
Nat Genet. 2015 Aug;47(8):921-5
pubmed: 26098870
Nat Genet. 2015 Mar;47(3):296-303
pubmed: 25621458
Nat Commun. 2020 Jan 14;11(1):255
pubmed: 31937769
Nature. 2015 Oct 1;526(7571):75-81
pubmed: 26432246
Am J Hum Genet. 2018 Sep 6;103(3):338-348
pubmed: 30100085
Am J Hum Genet. 2011 May 13;88(5):586-98
pubmed: 21565292
Am J Hum Genet. 2019 Aug 1;105(2):373-383
pubmed: 31353025
Nat Genet. 2015 Jun;47(6):589-97
pubmed: 25961943
Genetics. 2014 Oct;198(2):497-508
pubmed: 25104515
Genet Med. 2019 Apr;21(4):798-812
pubmed: 30655598
Heredity (Edinb). 2005 Sep;95(3):221-7
pubmed: 16077740
PLoS Genet. 2014 Jul 31;10(7):e1004494
pubmed: 25078778
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17626-31
pubmed: 17101969
Nucleic Acids Res. 2003 Jan 1;31(1):51-4
pubmed: 12519945
Nat Commun. 2018 Jul 4;9(1):2606
pubmed: 29973585
Nat Genet. 2013 Nov;45(11):1274-1283
pubmed: 24097068
Nature. 2020 Sep;585(7823):79-84
pubmed: 32663838
Curr Protoc Hum Genet. 2014 Apr 24;81:7.23.1-21
pubmed: 24763994
Nature. 2020 May;581(7809):444-451
pubmed: 32461652
Nat Commun. 2018 Oct 2;9(1):4038
pubmed: 30279509
Nat Genet. 2010 Apr;42(4):348-54
pubmed: 20208533
Circ Res. 2016 May 27;118(11):1752-70
pubmed: 27230640
J Mol Evol. 1994 Aug;39(2):174-90
pubmed: 7932781
Biomed Res Int. 2015;2015:671349
pubmed: 26339629
Nature. 2017 Oct 11;550(7675):239-243
pubmed: 29022581
Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012
pubmed: 30445434
Nat Genet. 2012 Jan 29;44(3):269-76
pubmed: 22286219
Curr Cardiol Rev. 2018;14(3):153-163
pubmed: 29473518
Brief Funct Genomics. 2015 Sep;14(5):339-51
pubmed: 25903743
Am J Clin Pathol. 2004 Jun;121 Suppl:S97-104
pubmed: 15298155
PLoS Genet. 2012;8(8):e1002907
pubmed: 22916037
Genome Res. 2011 Jun;21(6):974-84
pubmed: 21324876
Nature. 2020 Jul;583(7814):83-89
pubmed: 32460305
Nature. 2019 Aug;572(7769):323-328
pubmed: 31367044
Nat Methods. 2015 Oct;12(10):966-8
pubmed: 26258291
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Science. 2008 May 9;320(5877):807-11
pubmed: 18467591
Nat Commun. 2016 Mar 23;7:11122
pubmed: 27005778
Genome Biol. 2020 Aug 10;21(1):202
pubmed: 32778141
Brief Bioinform. 2013 Mar;14(2):178-92
pubmed: 22517427

Auteurs

Lei Chen (L)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.

Haley J Abel (HJ)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Indraniel Das (I)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.

David E Larson (DE)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Liron Ganel (L)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Krishna L Kanchi (KL)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.

Allison A Regier (AA)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Erica P Young (EP)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Chul Joo Kang (CJ)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.

Alexandra J Scott (AJ)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Colby Chiang (C)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Xinxin Wang (X)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.

Shuangjia Lu (S)

Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.

Ryan Christ (R)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.

Susan K Service (SK)

Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.

Charleston W K Chiang (CWK)

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.

Aki S Havulinna (AS)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland; Finnish Institute for Health and Welfare (THL), Helsinki 00271, Finland.

Johanna Kuusisto (J)

Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio 70210, Finland; Department of Medicine, Kuopio University Hospital, Kuopio 70210, Finland.

Michael Boehnke (M)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

Markku Laakso (M)

Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio 70210, Finland; Department of Medicine, Kuopio University Hospital, Kuopio 70210, Finland.

Aarno Palotie (A)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland; Analytical and Translational Genetics Unit (ATGU), Psychiatric & Neurodevelopmental Genetics Unit, Departments of Psychiatry and Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Samuli Ripatti (S)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland.

Nelson B Freimer (NB)

Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.

Adam E Locke (AE)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Nathan O Stitziel (NO)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: nstitziel@wustl.edu.

Ira M Hall (IM)

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: ira.hall@yale.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Allèles › Association of structural variation with...
questionsmedicales.fr › Maladies cardiovasculaires › Association of structural variation with...
questionsmedicales.fr › Lipides › Lipides membranaires › Stérols › Cholestérol › Association of structural variation with...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Association of structural variation with...
questionsmedicales.fr › Régions géographiques › Europe › Pays nordiques et scandinaves › Finlande › Association of structural variation with...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome humain › Association of structural variation with...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Association of structural variation with...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Association of structural variation with...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Séquençage nucléotidique à haut débit › Association of structural variation with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Association of structural variation with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines mitochondriales › Association of structural variation with...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Association of structural variation with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphoprotein Phosphatases › Pyruvate dehydrogenase (lipoamide)-phosphatase › Association of structural variation with...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Cétoacides › Pyruvates › Acide pyruvique › Association of structural variation with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Sérumalbumine › Sérum-albumine humaine › Association of structural variation with...