Identification of genetic loci simultaneously associated with multiple cardiometabolic traits.
Cardiometabolic disease
Epidemiology
Fat distribution
GWAS
Pleiotropy
Risk alleles
Risk factors
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
02
07
2021
revised:
09
12
2021
accepted:
04
01
2022
pubmed:
17
2
2022
medline:
13
4
2022
entrez:
16
2
2022
Statut:
ppublish
Résumé
Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits. We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple loci reached genome-wide levels of significance (N = 145-333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10 Our analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets.
Sections du résumé
BACKGROUND AND AIMS
Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.
METHODS AND RESULTS
We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple loci reached genome-wide levels of significance (N = 145-333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10
CONCLUSIONS
Our analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets.
Identifiants
pubmed: 35168826
pii: S0939-4753(22)00017-5
doi: 10.1016/j.numecd.2022.01.002
pmc: PMC9275655
mid: NIHMS1770183
pii:
doi:
Substances chimiques
Cholesterol, HDL
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1027-1034Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG006139
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136528
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD087860
Pays : United States
Informations de copyright
Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have no relevant conflicts of interest to disclose.
Références
Nat Genet. 2017 Dec;49(12):1758-1766
pubmed: 29083408
Nat Genet. 2010 Nov;42(11):949-60
pubmed: 20935629
Arch Intern Med. 2008 Aug 11;168(15):1617-24
pubmed: 18695075
Nat Genet. 2013 Nov;45(11):1274-1283
pubmed: 24097068
Am J Clin Nutr. 2008 Nov;88(5):1263-71
pubmed: 18996861
Ann Epidemiol. 1990 Oct;1(1):33-48
pubmed: 1669488
Nat Commun. 2016 Feb 01;7:10495
pubmed: 26833246
Curr Diab Rep. 2018 Jun 25;18(8):59
pubmed: 29938349
J Intern Med. 2018 Nov;284(5):450-463
pubmed: 30144199
PLoS Genet. 2019 Dec 12;15(12):e1008489
pubmed: 31830040
Nat Genet. 2017 Oct;49(10):1450-1457
pubmed: 28869590
Nature. 2015 Feb 12;518(7538):187-196
pubmed: 25673412
PLoS Genet. 2013;9(8):e1003681
pubmed: 23966867
Diabetes. 2020 Oct;69(10):2194-2205
pubmed: 32493714
PLoS Genet. 2012;8(3):e1002637
pubmed: 22479213
Nat Genet. 2012 Sep;44(9):981-90
pubmed: 22885922
JAMA. 2011 Jun 22;305(24):2556-64
pubmed: 21693744
Nat Genet. 2018 Apr;50(4):572-580
pubmed: 29632379
Am J Cardiol. 2011 Nov 15;108(10):1426-31
pubmed: 21855834
PLoS Med. 2017 Sep 12;14(9):e1002383
pubmed: 28898252
Am J Epidemiol. 1997 Apr 1;145(7):614-9
pubmed: 9098178
Obesity (Silver Spring). 2006 Feb;14(2):336-41
pubmed: 16571861
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Nat Genet. 2018 Jul;50(7):906-908
pubmed: 29892013
Br Med J (Clin Res Ed). 1984 Nov 10;289(6454):1257-61
pubmed: 6437507
Nat Genet. 2019 Jul;51(7):1082-1091
pubmed: 31253980
JAMA. 2016 Oct 4;316(13):1383-1391
pubmed: 27701660
Hum Mol Genet. 2016 Sep 15;25(18):4094-4106
pubmed: 27466198
Nat Genet. 2017 Mar;49(3):403-415
pubmed: 28135244
J Am Heart Assoc. 2018 Aug 7;7(15):e009271
pubmed: 30371251
Am J Hum Genet. 2019 Jan 3;104(1):65-75
pubmed: 30595370
PLoS Genet. 2013 Jun;9(6):e1003500
pubmed: 23754948
Nat Genet. 2019 Jul;51(7):1073-1075
pubmed: 31253975
Circulation. 2003 Apr 1;107(12):1626-31
pubmed: 12668497
Lancet. 2010 Feb 27;375(9716):735-42
pubmed: 20167359
Atherosclerosis. 1991 Feb;86(2-3):251-60
pubmed: 1872918
Nat Commun. 2021 Feb 3;12(1):764
pubmed: 33536417
Mol Genet Metab. 2011 Dec;104(4):666-9
pubmed: 21963081
PLoS Med. 2020 Mar 23;17(3):e1003062
pubmed: 32203549
Nature. 2010 Aug 5;466(7307):707-13
pubmed: 20686565
Can J Cardiol. 2013 Jan;29(1):37-45
pubmed: 23261319
Obesity (Silver Spring). 2009 Aug;17(8):1581-7
pubmed: 19407809
Nat Genet. 2015 Oct;47(10):1121-1130
pubmed: 26343387
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
Diabetes Care. 1994 Sep;17(9):961-9
pubmed: 7988316
Nat Genet. 2010 Jul;42(7):579-89
pubmed: 20581827
Diabetes. 2019 Jan;68(1):207-219
pubmed: 30352878
Am J Clin Nutr. 2012 Oct;96(4):714-26
pubmed: 22932278
Pediatrics. 2013 Mar;131(3):e679-86
pubmed: 23420920
Nat Genet. 2017 Jan;49(1):54-64
pubmed: 27841878
Diabetes. 2016 Aug;65(8):2448-60
pubmed: 27207519
Diabetologia. 1976 Dec;12(6):563-71
pubmed: 187517
Bioinformatics. 2016 Jul 1;32(13):1981-9
pubmed: 27153689
BMJ Open Diabetes Res Care. 2017 Oct 10;5(1):e000438
pubmed: 29081977
J Allergy Clin Immunol. 2020 Feb;145(2):537-549
pubmed: 31669095
Food Nutr Bull. 2004 Sep;25(3):292-302
pubmed: 15460274
Hum Mol Genet. 2019 Dec 15;28(24):4161-4172
pubmed: 31691812
Lancet Diabetes Endocrinol. 2014 Aug;2(8):634-47
pubmed: 24842598
Cardiovasc Diabetol. 2011 Nov 03;10:96
pubmed: 22050728
Nat Genet. 2018 Apr;50(4):524-537
pubmed: 29531354
J Am Coll Cardiol. 2015 Apr 21;65(15):1552-61
pubmed: 25770315
Nat Genet. 2011 Aug 28;43(10):984-9
pubmed: 21874001
Metabolites. 2021 Oct 09;11(10):
pubmed: 34677406
JAMA. 2018 Dec 25;320(24):2553-2563
pubmed: 30575882