Dataset Information

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

ABSTRACT: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD.We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD.We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10(??) were tested for association with CAD in 31,400 cases and 92,927 controls.Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 × 10??), SLC17A3 (1.0 × 10??), GTPB10 (1.7 × 10??), CUBN (7.5 × 10?¹?), HNF1A (1.2 × 10?¹²)), and FUT2 (6.6 × 10??), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-?mol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 × 10?³?). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49).We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD.

SUBMITTER: van Meurs JB

PROVIDER: S-EPMC4321227 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

van Meurs Joyce B J JB Pare Guillaume G Schwartz Stephen M SM Hazra Aditi A Tanaka Toshiko T Vermeulen Sita H SH Cotlarciuc Ioana I Yuan Xin X Mälarstig Anders A Bandinelli Stefania S Bis Joshua C JC Blom Henk H Brown Morris J MJ Chen Constance C Chen Yii-Der YD Clarke Robert J RJ Dehghan Abbas A Erdmann Jeanette J Ferrucci Luigi L Hamsten Anders A Hofman Albert A Hunter David J DJ Goel Anuj A Johnson Andrew D AD Kathiresan Sekar S Kampman Ellen E Kiel Douglas P DP Kiemeney Lambertus A L M LA Chambers John C JC Kraft Peter P Lindemans Jan J McKnight Barbara B Nelson Christopher P CP O'Donnell Christopher J CJ Psaty Bruce M BM Ridker Paul M PM Rivadeneira Fernando F Rose Lynda M LM Seedorf Udo U Siscovick David S DS Schunkert Heribert H Selhub Jacob J Ueland Per M PM Vollenweider Peter P Waeber Gérard G Waterworth Dawn M DM Watkins Hugh H Witteman Jacqueline C M JC den Heijer Martin M Jacques Paul P Uitterlinden Andre G AG Kooner Jaspal S JS Rader Dan J DJ Reilly Muredach P MP Mooser Vincent V Chasman Daniel I DI Samani Nilesh J NJ Ahmadi Kourosh R KR

The American journal of clinical nutrition 20130703 3

<h4>Background</h4>The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD.<h4>Objective</h4>We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD.<h4>Design</h4>We conducted a meta-analysis of geno ...[more]

PMID: 23824729

Similar Datasets

Project description:BackgroundComorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks.MethodsBy leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs).FindingsBriefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18-0.19) to 0.23 (95% CI 0.23-0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks.InterpretationFive SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of 'Long COVID-19.'

Dataset Information

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

Publications

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets