Role of Adiponectin in Coronary Heart Disease Risk: A Mendelian Randomization Study

Maria Carolina Borges; Debbie A Lawlor; Cesar de Oliveira; Jon White; Bernardo Lessa Horta; Aluísio J D Barros

doi:10.1161/CIRCRESAHA.116.308716

Role of Adiponectin in Coronary Heart Disease Risk: A Mendelian Randomization Study

Maria Carolina Borges, Debbie A Lawlor, Cesar de Oliveira, Jon White, Bernardo Lessa Horta, Aluísio J D Barros

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Abstract

RATIONALE: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis.

OBJECTIVE: We aimed to investigate the causal effect of adiponectin on CHD risk.

METHODS AND RESULTS: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68-1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84-1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors.

CONCLUSIONS: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis.

Original language	English
Pages (from-to)	491-499
Number of pages	9
Journal	Circulation Research
Volume	119
Issue number	3
Early online date	1 Jun 2016
DOIs	https://doi.org/10.1161/CIRCRESAHA.116.308716
Publication status	Published - 22 Jul 2016

Keywords

adiponectin
cardiovascular disease
coronary artery disease
Mendelian randomization analysis obesity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/CIRCRESAHA.116.308716

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MRC UoB UNITE Unit - Programme 5
Lawlor, D. A. (Principal Investigator) & Lawlor, D. A. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research

Dr Maria C Borges
- m.c.borgesbristol.acuk
- Bristol Medical School (PHS) - Associate Professor in Aetiological Epidemiology
- Bristol Population Health Science Institute
Person: Academic , Member
Professor Debbie A Lawlor
- D.A.Lawlorbristol.acuk
- Bristol Medical School (PHS) - Professor of Epidemiology, MRC Investigator and BHF Chair
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
Person: Academic , Member

Cite this

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title = "Role of Adiponectin in Coronary Heart Disease Risk: A Mendelian Randomization Study",

abstract = "RATIONALE: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis.OBJECTIVE: We aimed to investigate the causal effect of adiponectin on CHD risk.METHODS AND RESULTS: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68-1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84-1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors.CONCLUSIONS: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis.",

keywords = "adiponectin, cardiovascular disease, coronary artery disease, Mendelian randomization analysis obesity",

author = "Borges, {Maria Carolina} and Lawlor, {Debbie A} and {de Oliveira}, Cesar and Jon White and Horta, {Bernardo Lessa} and Barros, {Alu{\'i}sio J D}",

note = "{\textcopyright} 2016 The Authors.",

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doi = "10.1161/CIRCRESAHA.116.308716",

language = "English",

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pages = "491--499",

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TY - JOUR

T1 - Role of Adiponectin in Coronary Heart Disease Risk

T2 - A Mendelian Randomization Study

AU - Borges, Maria Carolina

AU - Lawlor, Debbie A

AU - de Oliveira, Cesar

AU - White, Jon

AU - Horta, Bernardo Lessa

AU - Barros, Aluísio J D

PY - 2016/7/22

Y1 - 2016/7/22

N2 - RATIONALE: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis.OBJECTIVE: We aimed to investigate the causal effect of adiponectin on CHD risk.METHODS AND RESULTS: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68-1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84-1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors.CONCLUSIONS: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis.

AB - RATIONALE: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis.OBJECTIVE: We aimed to investigate the causal effect of adiponectin on CHD risk.METHODS AND RESULTS: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68-1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84-1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors.CONCLUSIONS: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis.

KW - adiponectin

KW - cardiovascular disease

KW - coronary artery disease

KW - Mendelian randomization analysis obesity

U2 - 10.1161/CIRCRESAHA.116.308716

DO - 10.1161/CIRCRESAHA.116.308716

M3 - Article (Academic Journal)

C2 - 27252388

SN - 0009-7330

VL - 119

SP - 491

EP - 499

JO - Circulation Research

JF - Circulation Research

IS - 3

ER -

Role of Adiponectin in Coronary Heart Disease Risk: A Mendelian Randomization Study

Abstract

Keywords

UN SDGs

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Projects

MRC UoB UNITE Unit - Programme 5

Profiles

Dr Maria C Borges

Professor Debbie A Lawlor

Cite this