Effects of protein-coding variants on blood metabolite measurements and clinical biomarkers in the UK Biobank.
metabolomics, UK Biobank, rare variant, collapsing analyses, metabologenomics, mQTL, exome sequencing
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:
02 03 2023
02 03 2023
Historique:
received:
21
11
2022
accepted:
30
01
2023
pubmed:
23
2
2023
medline:
8
3
2023
entrez:
22
2
2023
Statut:
ppublish
Résumé
Genome-wide association studies (GWASs) have established the contribution of common and low-frequency variants to metabolic blood measurements in the UK Biobank (UKB). To complement existing GWAS findings, we assessed the contribution of rare protein-coding variants in relation to 355 metabolic blood measurements-including 325 predominantly lipid-related nuclear magnetic resonance (NMR)-derived blood metabolite measurements (Nightingale Health Plc) and 30 clinical blood biomarkers-using 412,393 exome sequences from four genetically diverse ancestries in the UKB. Gene-level collapsing analyses were conducted to evaluate a diverse range of rare-variant architectures for the metabolic blood measurements. Altogether, we identified significant associations (p < 1 × 10
Identifiants
pubmed: 36809768
pii: S0002-9297(23)00046-0
doi: 10.1016/j.ajhg.2023.02.002
pmc: PMC10027475
pii:
doi:
Substances chimiques
Biomarkers
0
Lipids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
487-498Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.N., R.S.D., L.M., X.J., D.V., E.W., E.L.A., A.R., K.C., K.R.S., Q.W., B.C., D.S.P., A.R.H., and S.P. are current employees and/or stockholders of AstraZeneca.
Références
Nat Genet. 2021 Feb;53(2):185-194
pubmed: 33462484
PLoS Med. 2017 Sep 12;14(9):e1002383
pubmed: 28898252
Arch Biochem Biophys. 2016 Jan 1;589:168-76
pubmed: 26432701
PLoS One. 2016 Apr 13;11(4):e0153672
pubmed: 27073872
Am J Hum Genet. 2018 May 3;102(5):717-730
pubmed: 29727686
Am J Respir Crit Care Med. 2017 Jul 1;196(1):82-93
pubmed: 28099038
Nat Genet. 2021 Aug;53(8):1260-1269
pubmed: 34226706
Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082
pubmed: 29126136
Genome Res. 2017 Oct;27(10):1715-1729
pubmed: 28864458
Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1225-36
pubmed: 18565848
Sci Rep. 2017 Sep 8;7(1):11008
pubmed: 28887542
JCI Insight. 2020 Mar 12;5(5):
pubmed: 32161197
Int J Epidemiol. 2017 Oct 5;47(1):29-35
pubmed: 29040602
Science. 2021 Jul 2;373(6550):
pubmed: 34210852
Nat Commun. 2018 Jan 23;9(1):333
pubmed: 29362361
Elife. 2021 Feb 15;10:
pubmed: 33587031
Nat Genet. 2017 Apr;49(4):568-578
pubmed: 28263315
Nat Genet. 2014 Jun;46(6):543-550
pubmed: 24816252
Sci Adv. 2022 Nov 18;8(46):eadd5430
pubmed: 36383675
Nat Genet. 2019 Jun;51(6):957-972
pubmed: 31152163
Nat Genet. 2011 Jun;43(6):565-9
pubmed: 21572414
Nature. 2015 Oct 1;526(7571):82-90
pubmed: 26367797
N Engl J Med. 2018 Mar 22;378(12):1096-1106
pubmed: 29562163
N Engl J Med. 2006 Mar 23;354(12):1264-72
pubmed: 16554528
Sci Data. 2023 Jan 31;10(1):64
pubmed: 36720882
Nat Genet. 2013 Nov;45(11):1274-1283
pubmed: 24097068
Nat Genet. 2011 Oct 16;43(11):1131-8
pubmed: 22001757
N Engl J Med. 2011 Feb 24;364(8):740-8
pubmed: 21345103
Elife. 2022 Sep 08;11:
pubmed: 36073519
PLoS Genet. 2017 Oct 30;13(10):e1007079
pubmed: 29084231
Nat Commun. 2016 Jul 25;7:12360
pubmed: 27453504
Nat Commun. 2022 Mar 28;13(1):1644
pubmed: 35347128
Fly (Austin). 2012 Apr-Jun;6(2):80-92
pubmed: 22728672
Nat Genet. 2012 Jan 29;44(3):269-76
pubmed: 22286219
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
Eur J Hum Genet. 2016 Aug;24(8):1202-5
pubmed: 26733288
Am J Hum Genet. 2016 Oct 6;99(4):877-885
pubmed: 27666373
Sci Rep. 2021 Nov 3;11(1):21565
pubmed: 34732801
J Clin Endocrinol Metab. 2022 May 17;107(6):e2318-e2323
pubmed: 35235652
Science. 2012 Feb 17;335(6070):823-8
pubmed: 22344438
Nat Genet. 2022 Mar;54(3):240-250
pubmed: 35177841
Nat Genet. 2021 Jul;53(7):942-948
pubmed: 34183854
Sci Rep. 2016 Jun 13;6:27857
pubmed: 27291420
Am J Hum Genet. 2022 Jun 2;109(6):1038-1054
pubmed: 35568032
Nature. 2021 Sep;597(7877):527-532
pubmed: 34375979
Bioinformatics. 2010 Nov 15;26(22):2867-73
pubmed: 20926424
Nat Genet. 2018 Nov;50(11):1514-1523
pubmed: 30275531
Sci Rep. 2021 Sep 29;11(1):19400
pubmed: 34588527