The shared allelic architecture of adiponectin levels and coronary artery disease

TY - JOUR

T1 - The shared allelic architecture of adiponectin levels and coronary artery disease

AU - Dastani, Zari

AU - Johnson, Toby

AU - Kronenberg, Florian

AU - Nelson, Christopher P

AU - Assimes, Themistocles L

AU - März, Winfried

AU - Richards, J Brent

AU - CARDIoGRAM Consortium

AU - Blankenberg, Stefan

N1 - Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

PY - 2013/7

Y1 - 2013/7

N2 - OBJECTIVE: A large body of epidemiologic data strongly suggests an association between excess adiposity and coronary artery disease (CAD). Low adiponectin levels, a hormone secreted only from adipocytes, have been associated with an increased risk of CAD in observational studies. However, these associations cannot clarify whether this relationship is causal or due to a shared set of causal factors or even confounding. Genome-wide association studies have identified common variants that influence adiponectin levels, providing valuable tools to examine the genetic relationship between adiponectin and CAD.METHODS: Using 145 genome wide significant SNPs for adiponectin from the ADIPOGen consortium (n = 49,891), we tested whether adiponectin-decreasing alleles influenced risk of CAD in the CARDIoGRAM consortium (n = 85,274).RESULTS: In single-SNP analysis, 5 variants among 145 SNPs were associated with increased risk of CAD after correcting for multiple testing (P < 4.4 × 10(-4)). Using a multi-SNP genotypic risk score to test whether adiponectin levels and CAD have a shared genetic etiology, we found that adiponectin-decreasing alleles increased risk of CAD (P = 5.4 × 10(-7)).CONCLUSION: These findings demonstrate that adiponectin levels and CAD have a shared allelic architecture and provide rationale to undertake a Mendelian randomization studies to understand if this relationship is causal.

AB - OBJECTIVE: A large body of epidemiologic data strongly suggests an association between excess adiposity and coronary artery disease (CAD). Low adiponectin levels, a hormone secreted only from adipocytes, have been associated with an increased risk of CAD in observational studies. However, these associations cannot clarify whether this relationship is causal or due to a shared set of causal factors or even confounding. Genome-wide association studies have identified common variants that influence adiponectin levels, providing valuable tools to examine the genetic relationship between adiponectin and CAD.METHODS: Using 145 genome wide significant SNPs for adiponectin from the ADIPOGen consortium (n = 49,891), we tested whether adiponectin-decreasing alleles influenced risk of CAD in the CARDIoGRAM consortium (n = 85,274).RESULTS: In single-SNP analysis, 5 variants among 145 SNPs were associated with increased risk of CAD after correcting for multiple testing (P < 4.4 × 10(-4)). Using a multi-SNP genotypic risk score to test whether adiponectin levels and CAD have a shared genetic etiology, we found that adiponectin-decreasing alleles increased risk of CAD (P = 5.4 × 10(-7)).CONCLUSION: These findings demonstrate that adiponectin levels and CAD have a shared allelic architecture and provide rationale to undertake a Mendelian randomization studies to understand if this relationship is causal.

KW - Adiponectin/genetics

KW - Adiposity/genetics

KW - Alleles

KW - Atherosclerosis/epidemiology

KW - Coronary Artery Disease/epidemiology

KW - Databases, Genetic

KW - Genetic Predisposition to Disease/epidemiology

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Prevalence

KW - Risk Factors

U2 - 10.1016/j.atherosclerosis.2013.03.034

DO - 10.1016/j.atherosclerosis.2013.03.034

M3 - SCORING: Journal article

C2 - 23664276

VL - 229

SP - 145

EP - 148

JO - ATHEROSCLEROSIS

JF - ATHEROSCLEROSIS

SN - 0021-9150

IS - 1

ER -