Mendelian randomization prioritizes abdominal adiposity as an independent causal factor for liver fat accumulation and cardiometabolic diseases.

Heart failure Type 2 diabetes

Journal

Communications medicine
ISSN: 2730-664X
Titre abrégé: Commun Med (Lond)
Pays: England
ID NLM: 9918250414506676

Informations de publication

Date de publication:
2022
Historique:
received: 07 02 2022
accepted: 29 09 2022
entrez: 17 10 2022
pubmed: 18 10 2022
medline: 18 10 2022
Statut: epublish

Résumé

Observational studies have linked adiposity and especially abdominal adiposity to liver fat accumulation and non-alcoholic fatty liver disease. These traits are also associated with type 2 diabetes and coronary artery disease but the causal factor(s) underlying these associations remain unexplored. We used a multivariable Mendelian randomization study design to determine whether body mass index and waist circumference were causally associated with non-alcoholic fatty liver disease using publicly available genome-wide association study summary statistics of the UK Biobank ( Using multivariable Mendelian randomization we show that waist circumference increase non-alcoholic fatty liver disease risk even when accounting for body mass index (odd ratio per 1-standard deviation increase = 2.35 95% CI = 1.31-4.22, These results identify waist circumference as a strong, independent, and causal contributor to non-alcoholic fatty liver disease, type 2 diabetes and coronary artery disease, thereby highlighting the importance of assessing body fat distribution for the prediction and prevention of cardiometabolic diseases.

Sections du résumé

Background UNASSIGNED
Observational studies have linked adiposity and especially abdominal adiposity to liver fat accumulation and non-alcoholic fatty liver disease. These traits are also associated with type 2 diabetes and coronary artery disease but the causal factor(s) underlying these associations remain unexplored.
Methods UNASSIGNED
We used a multivariable Mendelian randomization study design to determine whether body mass index and waist circumference were causally associated with non-alcoholic fatty liver disease using publicly available genome-wide association study summary statistics of the UK Biobank (
Results UNASSIGNED
Using multivariable Mendelian randomization we show that waist circumference increase non-alcoholic fatty liver disease risk even when accounting for body mass index (odd ratio per 1-standard deviation increase = 2.35 95% CI = 1.31-4.22,
Conclusions UNASSIGNED
These results identify waist circumference as a strong, independent, and causal contributor to non-alcoholic fatty liver disease, type 2 diabetes and coronary artery disease, thereby highlighting the importance of assessing body fat distribution for the prediction and prevention of cardiometabolic diseases.

Identifiants

pubmed: 36249462
doi: 10.1038/s43856-022-00196-3
pii: 196
pmc: PMC9561122
doi:

Types de publication

Journal Article

Langues

eng

Pagination

130

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Informations de copyright

© The Author(s) 2022.

Déclaration de conflit d'intérêts

Competing interestsThe authors declare the following competing interests: B.J.A. is a consultant for Novartis and Silence Therapeutics and has received research contracts from Pfizer, Ionis Pharmaceuticals and Silence Therapeutics. A.T. receives research funding from Johnson & Johnson Medical Companies, Medtronic, Bodynov, and GI Windows for studies on bariatric surgery and received consulting fees from Novo Nordisk and Bausch Health. All other authors declare no competing interests.

Références

Hepatology. 2018 Jan;67(1):328-357
pubmed: 28714183
Stat Med. 2021 Nov 20;40(26):5813-5830
pubmed: 34342032
Nat Rev Gastroenterol Hepatol. 2017 Jan;14(1):32-42
pubmed: 27729660
Atherosclerosis. 2010 Aug;211(2):565-73
pubmed: 20594555
Physiol Rev. 2013 Jan;93(1):359-404
pubmed: 23303913
Lancet Diabetes Endocrinol. 2019 Sep;7(9):715-725
pubmed: 31301983
PLoS Med. 2020 Apr 30;17(4):e1003100
pubmed: 32353039
Elife. 2021 Jun 15;10:
pubmed: 34128465
Genet Epidemiol. 2012 Apr;36(3):214-24
pubmed: 22714935
Gastroenterology. 2011 Oct;141(4):1249-53
pubmed: 21726509
Nature. 2015 Feb 12;518(7538):187-196
pubmed: 25673412
JAMA. 2017 Feb 14;317(6):626-634
pubmed: 28196256
Genet Epidemiol. 2020 Jun;44(4):313-329
pubmed: 32249995
Diabetes. 2017 Nov;66(11):2888-2902
pubmed: 28566273
Lancet Diabetes Endocrinol. 2022 Jun;10(6):393-406
pubmed: 35468325
Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):27-38
pubmed: 17690317
Cell Rep Med. 2021 Nov 03;2(11):100437
pubmed: 34841290
Hepatology. 2016 Jul;64(1):73-84
pubmed: 26707365
Nat Commun. 2020 Jan 17;11(1):376
pubmed: 31953392
Int J Epidemiol. 2003 Feb;32(1):1-22
pubmed: 12689998
Endocr Rev. 2022 Jan 12;43(1):35-60
pubmed: 34100954
Nat Rev Endocrinol. 2020 Mar;16(3):177-189
pubmed: 32020062
JAMA. 2008 Mar 12;299(10):1185-7
pubmed: 18334695
Elife. 2018 May 30;7:
pubmed: 29846171
Obes Rev. 2012 Dec;13 Suppl 2:30-9
pubmed: 23107257
Sci Rep. 2018 May 8;8(1):7146
pubmed: 29739994
J Clin Endocrinol Metab. 2016 Mar;101(3):945-52
pubmed: 26672639
Int J Epidemiol. 2019 Jun 1;48(3):713-727
pubmed: 30535378
Eur Heart J. 2018 Feb 1;39(5):385-393
pubmed: 29228164
Annu Rev Genomics Hum Genet. 2018 Aug 31;19:303-327
pubmed: 29709202
Am J Epidemiol. 2015 Feb 15;181(4):251-60
pubmed: 25632051
Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1927-32
pubmed: 21546603
Int J Epidemiol. 2011 Jun;40(3):755-64
pubmed: 21414999
Int J Epidemiol. 2015 Apr;44(2):512-25
pubmed: 26050253
Am J Cardiol. 2015 Feb 1;115(3):307-15
pubmed: 25499404
Nat Genet. 2018 May;50(5):693-698
pubmed: 29686387
Stat Med. 2021 Nov 10;40(25):5434-5452
pubmed: 34338327
Int J Epidemiol. 2017 Dec 1;46(6):1734-1739
pubmed: 28398548
N Engl J Med. 2010 May 6;362(18):1675-85
pubmed: 20427778
N Engl J Med. 2021 Mar 25;384(12):1113-1124
pubmed: 33185364
Int J Epidemiol. 2006 Feb;35(1):83-92
pubmed: 16339600
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Int J Epidemiol. 2011 Jun;40(3):740-52
pubmed: 20813862
Stat Med. 2017 Dec 20;36(29):4705-4718
pubmed: 28960498
BMC Med. 2019 Jul 17;17(1):135
pubmed: 31311600
Nat Genet. 2015 Oct;47(10):1121-1130
pubmed: 26343387
Circ Res. 2018 Feb 2;122(3):433-443
pubmed: 29212778
J Hepatol. 2020 Aug;73(2):263-276
pubmed: 32165250
Nat Genet. 2018 Nov;50(11):1505-1513
pubmed: 30297969
J Econom. 2016 Feb;190(2):212-221
pubmed: 29129953
Eur J Epidemiol. 2018 Oct;33(10):947-952
pubmed: 30039250
J Clin Endocrinol Metab. 2016 Aug;101(8):3212-21
pubmed: 27285293
J Clin Endocrinol Metab. 2010 Jan;95(1):93-9
pubmed: 19906786
Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15430-5
pubmed: 19706383
J Gastroenterol. 2013 Mar;48(3):413-22
pubmed: 22933183
Circulation. 2018 Mar 13;137(11):1143-1157
pubmed: 29142011
Hum Mol Genet. 2019 Jan 1;28(1):166-174
pubmed: 30239722
Nature. 2015 Feb 12;518(7538):197-206
pubmed: 25673413
Genetics. 2017 Oct;207(2):481-487
pubmed: 28835472
Nat Commun. 2018 May 16;9(1):1946
pubmed: 29769528
Diabetes. 2011 Jan;60(1):56-63
pubmed: 20956499
Obes Rev. 2016 Aug;17(8):664-90
pubmed: 27213481

Auteurs

Eloi Gagnon (E)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.

William Pelletier (W)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.

Émilie Gobeil (É)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.

Jérôme Bourgault (J)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.

Hasanga D Manikpurage (HD)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.

Ina Maltais-Payette (I)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.
School of Nutrition, Université Laval, Québec, QC Canada.

Erik Abner (E)

Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23b, Tartu, 51010 Estonia.

Nele Taba (N)

Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23b, Tartu, 51010 Estonia.
Institute of Molecular and Cell Biology, University of Tartu, Riia 23, Tartu, 51,010 Estonia.

Tõnu Esko (T)

Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23b, Tartu, 51010 Estonia.

Patricia L Mitchell (PL)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.

Nooshin Ghodsian (N)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.

Jean-Pierre Després (JP)

VITAM - Centre de recherche en santé durable, Université Laval, Québec, QC Canada.

Marie-Claude Vohl (MC)

School of Nutrition, Université Laval, Québec, QC Canada.
Centre NUTRISS, Institut sur la nutrition et les aliments fonctionnels, Université Laval, Québec, QC Canada.

André Tchernof (A)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.
School of Nutrition, Université Laval, Québec, QC Canada.

Sébastien Thériault (S)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.
Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec, QC Canada.

Benoit J Arsenault (BJ)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC Canada.
Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC Canada.

Classifications MeSH