The shared allelic architecture of adiponectin levels and coronary artery disease
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The shared allelic architecture of adiponectin levels and coronary artery disease. / Dastani, Zari; Johnson, Toby; Kronenberg, Florian; Nelson, Christopher P; Assimes, Themistocles L; März, Winfried; Richards, J Brent; CARDIoGRAM Consortium.
in: ATHEROSCLEROSIS, Jahrgang 229, Nr. 1, 07.2013, S. 145-148.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -