Robert Roberts

University of Ottawa, Ottawa, Ontario, Canada

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Publications (301)2769.53 Total impact

  • Majid Nikpay · Anuj Goel · Hong-Hee Won · Leanne M Hall · Christina Willenborg · Stavroula Kanoni · Danish Saleheen · Theodosios Kyriakou · Christopher P Nelson · Jemma C Hopewell · [...] · John R Thompson · Jeanette Erdmann · Robert Clarke · Hugh Watkins · Sekar Kathiresan · Ruth McPherson · Panos Deloukas · Heribert Schunkert · Nilesh J Samani · Martin Farrall
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    ABSTRACT: Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
    Nature Genetics 09/2015; DOI:10.1038/ng.3396 · 29.35 Impact Factor
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    ABSTRACT: Runs of homozygosity (ROHs) are recognized signature of recessive inheritance. Contributions of ROHs to the genetic architecture of coronary artery disease and regulation of gene expression in cells relevant to atherosclerosis are not known. Our combined analysis of 24,320 individuals from 11 populations of white European ethnicity showed an association between coronary artery disease and both the count and the size of ROHs. Individuals with coronary artery disease had approximately 0.63 (95% CI: 0.4-0.8) excess of ROHs when compared to coronary-artery-disease-free control subjects (p = 1.49 × 10(-9)). The average total length of ROHs was approximately 1,046.92 (95% CI: 634.4-1,459.5) kb greater in individuals with coronary artery disease than control subjects (p = 6.61 × 10(-7)). None of the identified individual ROHs was associated with coronary artery disease after correction for multiple testing. However, in aggregate burden analysis, ROHs favoring increased risk of coronary artery disease were much more common than those showing the opposite direction of association with coronary artery disease (p = 2.69 × 10(-33)). Individual ROHs showed significant associations with monocyte and macrophage expression of genes in their close proximity-subjects with several individual ROHs showed significant differences in the expression of 44 mRNAs in monocytes and 17 mRNAs in macrophages when compared to subjects without those ROHs. This study provides evidence for an excess of homozygosity in coronary artery disease in outbred populations and suggest the potential biological relevance of ROHs in cells of importance to the pathogenesis of atherosclerosis. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 07/2015; 97(2). DOI:10.1016/j.ajhg.2015.06.001 · 10.93 Impact Factor
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    ABSTRACT: -Statins lower low density lipoprotein cholesterol (LDL-C) and risk of coronary artery disease (CAD) but they may be ineffective or not tolerated. Bile acid sequestrants (BAS) reduce LDL-C yet their clinical efficacy on CAD remains controversial. -We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of cholestyramine and colesevelam. We then used Mendelian Randomization to estimate the effect of BAS on reducing the risk of CAD. First, we quantified the effect of rs4299376 (ABCG5/ABCG8), which affects the intestinal cholesterol absorption pathway targeted by BAS, and then we used these estimates to predict the effect of BAS on CAD. Nineteen RCTs with a total of 7,021 study participants were included. Cholestyramine 24g/d was associated with a reduction in LDL-C of 23.5 mg/dL (95% CI: -26.8,-20.2; N=3,806) and a trend towards reduced risk of CAD (OR: 0.81, 95% CI: 0.70-1.02; P=0.07; N=3,806) while colesevelam 3.75g/d was associated with a reduction in LDL-C of 22.7 mg/dL (95% CI: -28.3,-17.2; N=759). Based on the findings that rs4299376 was associated with a 2.75 mg/dL decrease in LDL-C and a 5% decrease in risk of CAD outcomes, we estimated that cholestyramine was associated with an OR for CAD of 0.63 (95% CI: 0.52 - 0.77; P= 6.3×10(-6)) and colesevelam with an OR of 0.64 (95% CI: 0.52-0.79, P: 4.3×10(-5)), which were not statistically different from BAS clinical trials (P>0.05). -The cholesterol lowering effect of BAS may translate into a clinically relevant reduction in CAD.
    Circulation Cardiovascular Genetics 06/2015; 8(4). DOI:10.1161/CIRCGENETICS.114.000952 · 4.60 Impact Factor
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    ABSTRACT: The mechanisms underlying the association between diabetes and coronary artery disease (CAD) risk are unclear. We aimed to assess this association by studying genetic variants that have been shown to associate with type 2 diabetes (T2DM). If the association between diabetes and CAD is causal, we expected to observe an association of these variants with CAD as well. We studied all genetic variants currently known to be associated with T2DM at a genome-wide significant level (p < 5*10(-8)) in CARDIoGRAM, a genome-wide data-set of CAD including 22,233 CAD cases and 64,762 controls. Out of the 44 published T2DM SNPs 10 were significantly associated with CAD in CARDIoGRAM (OR>1, p < 0.05), more than expected by chance (p = 5.0*10(-5)). Considering all 44 SNPs, the average CAD risk observed per individual T2DM risk allele was 1.0076 (95% confidence interval (CI), 0.9973-1.0180). Such average risk increase was significantly lower than the increase expected based on i) the published effects of the SNPs on T2DM risk and ii) the effect of T2DM on CAD risk as observed in the Framingham Heart Study, which suggested a risk of 1.067 per allele (p = 7.2*10(-10) vs. the observed effect). Studying two risk scores based on risk alleles of the diabetes SNPs, one score using individual level data in 9856 subjects, and the second score on average effects of reported beta-coefficients from the entire CARDIoGRAM data-set, we again observed a significant - yet smaller than expected - association with CAD. Our data indicate that an association between type 2 diabetes related SNPs and CAD exists. However, the effects on CAD risk appear to be by far lower than what would be expected based on the effects of risk alleles on T2DM and the effect of T2DM on CAD in the epidemiological setting. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Atherosclerosis 06/2015; 241(2):419-426. DOI:10.1016/j.atherosclerosis.2015.05.033 · 3.99 Impact Factor
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    ABSTRACT: Background: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. Methods: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. Results: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. Conclusions: There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.).
    New England Journal of Medicine 04/2015; 372(17). DOI:10.1056/NEJMoa1404881 · 55.87 Impact Factor
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    ABSTRACT: Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol16. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl−1. At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase15, 17 and apolipoprotein C-III. Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.
    Nature 12/2014; advance online publication. DOI:10.1038/nature13917 · 41.46 Impact Factor
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    ABSTRACT: Objective Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein (LDL) receptor. Mutations that block PCSK9 secretion reduce LDL-cholesterol and the incidence of myocardial infarction (MI). However, it remains unclear whether elevated plasma PCSK9 associates with coronary atherosclerosis (CAD) or more directly with rupture of the plaque causing MI. Methods and Results Plasma PCSK9 was measured by ELISA in 645 angiographically defined controls (<30% coronary stenosis) and 3,273 cases of CAD (>50% stenosis in a major coronary artery) from the Ottawa Heart Genomics Study. Because lipid lowering medications elevated plasma PCSK9, confounding association with disease, only individuals not taking a lipid lowering medication were considered (279 controls and 492 with CAD). Replication was sought in 357 controls and 465 with CAD from the Emory Cardiology Biobank study. PCSK9 levels were not associated with CAD in Ottawa, but were elevated with CAD in Emory. Plasma PCSK9 levels were elevated in 45 cases with acute MI (363.5±140.0 ng/ml) compared to 398 CAD cases without MI (302.0±91.3 ng/ml, p = 0.004) in Ottawa. This finding was replicated in the Emory study in 74 cases of acute MI (445.0±171.7 ng/ml) compared to 273 CAD cases without MI (369.9±139.1 ng/ml, p = 3.7×10−4). Since PCSK9 levels were similar in CAD patients with or without a prior (non-acute) MI, our finding suggests that plasma PCSK9 is elevated either immediately prior to or at the time of MI. Conclusion Plasma PCSK9 levels are increased with acute MI.
    PLoS ONE 09/2014; 9(9):e106294. DOI:10.1371/journal.pone.0106294 · 3.23 Impact Factor
  • Robert Roberts
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    ABSTRACT: There is almost no data on the genetics of acute coronary syndromes, so this review discusses primarily the 50 genetic risk variants associated with coronary artery disease that are of genome-wide significance in the discovery population and replicated in an independent population. All of these risk variants are extremely common with more than half occurring in >50% of the general population. They increased only minimally the relative risk for coronary artery disease. The most striking finding is that 35 of the 50 risk variants act independently of known risk factors, indicating there are several pathways yet to be appreciated, contributing to the pathogenesis of coronary atherosclerosis and myocardial infarction. All of the genetic variants seem to act through atherosclerosis, except for the ABO blood groups, which show that A and B are associated with increased risk for myocardial infarction, mediated by a prolonged von Willebrand plasma half life leading to thrombosis. The potential molecular mechanisms of 9p21 are discussed, including cell cycle kinase inhibitors. Discovery of risk variants associated with PCSK9 has led to the development of novel treatment for plasma low-density lipoprotein cholesterol. A monoclonal antibody inhibiting PCSK9 has already undergone phase I and II clinical trials, showing it is a potent inhibitor of low-density lipoprotein cholesterol and is mediated through more rapid removal of low-density lipoprotein cholesterol from the plasma. This therapy complements that of statin therapy, which inhibits the synthesis of cholesterol. The benefits of Mendelian randomization to assess safety and efficacy and their limitations are discussed along with future directions.
    Circulation Research 06/2014; 114(12):1890-903. DOI:10.1161/CIRCRESAHA.114.302692 · 11.02 Impact Factor
  • Sonny Dandona · Robert Roberts
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    ABSTRACT: Genome-wide association studies for coronary artery disease utilizing the case control association study approach has identified 50 genetic risk variants associated with coronary artery disease or myocardial infarction. All of these genetic variants are of genome wide significance and replicated in an independent population. It is of note that 35 of these 50 genetic risk variants act through mechanisms as yet unknown. These findings have great implications for the pathogenesis of atherosclerosis, as well as new targets for the development of novel therapies for the prevention and treatment of CAD. The genetic variant PCSK9 has already led to the development of a monoclonal anti-body which is undergoing assessment in phases I, II, and III clinical trials. This therapy shows very promising results and since it increases removal of LDL-C, it is complementary to current statin therapy. Assessing the beneficial or deleterious effects of a lifelong exposure to a genetic risk variant (Mendelian randomization) will be an important adjunct to clinical trials.
    Current Cardiology Reports 05/2014; 16(5):479. DOI:10.1007/s11886-014-0479-2 · 1.93 Impact Factor
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    ABSTRACT: Mitochondrial production of reactive oxygen species (ROS) affects many processes in health and disease. SPG7 assembles with AFG3L2 into the mAAA protease at the inner membrane of mitochondria, degrades damaged proteins, and regulates the synthesis of mitochondrial ribosomes. SPG7 is cleaved and activated by AFG3L2 upon assembly. A variant in SPG7 that replaces arginine 688 with glutamine (Q688) is associated with several phenotypes, including toxicity of chemotherapeutic agents, type 2 diabetes mellitus, and (as reported here) coronary artery disease. We demonstrate that SPG7 processing is regulated by tyrosine phosphorylation of AFG3L2. Carriers of Q688 bypass this regulation and constitutively process and activate SPG7 mAAA protease. Cells expressing Q688 produce higher ATP levels and ROS, promoting cell proliferation. Our results thus reveal an unexpected link between the phosphorylation-dependent regulation of the mitochondria mAAA protease affecting ROS production and several clinical phenotypes.
    Cell Reports 04/2014; 7(3). DOI:10.1016/j.celrep.2014.03.051 · 8.36 Impact Factor
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    ABSTRACT: Elevated levels of plasma trimethylamine N-oxide (TMAO), the product of gut microbiome and hepatic-mediated metabolism of dietary choline and l-carnitine, have recently been identified as a novel risk factor for the development of atherosclerosis in mice and humans. The goal of this study was to identify the genetic factors associated with plasma TMAO levels. We used comparative genome-wide association study approaches to discover loci for plasma TMAO levels in mice and humans. A genome-wide association study in the hybrid mouse diversity panel identified a locus for TMAO levels on chromosome 3 (P=2.37×10(-6)) that colocalized with a highly significant (P=1.07×10(-20)) cis-expression quantitative trait locus for solute carrier family 30 member 7. This zinc transporter could thus represent ≥1 positional candidate gene responsible for the association signal at this locus in mice. A genome-wide association study for plasma TMAO levels in 1973 humans identified 2 loci with suggestive evidence of association (P=3.0×10(-7)) on chromosomes 1q23.3 and 2p12. However, genotyping of the lead variants at these loci in 1892 additional subjects failed to replicate their association with plasma TMAO levels. The results of these limited observational studies indicate that, at least in humans, genes play a marginal role in determining TMAO levels and that any genetic effects are relatively weak and complex. Variation in diet or the repertoire of gut microbiota may be more important determinants of plasma TMAO levels in mice and humans, which should be investigated in future studies.
    Arteriosclerosis Thrombosis and Vascular Biology 03/2014; 34(6). DOI:10.1161/ATVBAHA.114.303252 · 6.00 Impact Factor
  • Robert Roberts
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    ABSTRACT: For a recent article in Science, Jiang et al1 used RNA inhibition to suppress specifically the expression of a mutant allele known to cause human familial hypertrophic cardiomyopathy. The RNA inhibition treatment prevented the development of familial hypertrophic cardiomyopathy in the mouse. This is an exciting, innovative finding which could pave the way for specific treatment of this disease in humans. If shown to be safe and effective, RNA inhibition could be applicable for many inherited autosomal dominant diseases.
    Circulation Research 02/2014; 114(5):751-3. DOI:10.1161/CIRCRESAHA.113.303179 · 11.02 Impact Factor
  • Scientific Sessions of the American-Heart-Association; 12/2013
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    ABSTRACT: Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype. Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5×10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (PIS=1.62×10(-7)) and ABO (PIS=2.6×10(-4)), as well as at HDAC9 (PLAS=2.32×10(-12)), 9p21 (PLAS=3.70×10(-6)), RAI1-PEMT-RASD1 (PLAS=2.69×10(-5)), EDNRA (PLAS=7.29×10(-4)), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10(-4)). Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.
    Stroke 11/2013; 45(1). DOI:10.1161/STROKEAHA.113.002707 · 5.72 Impact Factor
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    ABSTRACT: Pharmacogenetics in cardiovascular medicine brings the potential for personalized therapeutic strategies that improve efficacy and reduce harm. Studies evaluating the impact of genetic variation on pharmacologic effects have been undertaken for most major cardiovascular drugs, including antithrombotic agents, β-adrenergic receptor blockers, statins, and angiotensin-converting enzyme inhibitors. Across these drug classes, many polymorphisms associated with pharmacodynamic, pharmacokinetic, or surrogate outcomes have been identified. However, their impact on clinical outcomes and their ability to improve clinical practice remains unclear. This review will examine the current clinical evidence supporting pharmacogenetic testing in cardiovascular medicine, provide clinical guidance based on the current evidence, and identify further steps needed to determine the utility of pharmacogenetics in cardiovascular care.
    Clinical Cardiology 09/2013; 37(1). DOI:10.1002/clc.22200 · 2.59 Impact Factor
  • Robert Roberts
    The Canadian journal of cardiology 06/2013; 29(8). DOI:10.1016/j.cjca.2013.04.014 · 3.94 Impact Factor
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    ABSTRACT: Background: Variants at the 9p21 locus associate with the risk of coronary artery disease (CAD) or myocardial infarction (MI). However, atherosclerotic plaque deposition is distinct from MI (plaque rupture and thrombosis), and recent studies showed no association between these variants and MI in patients with preexisting CAD. We performed haplotype analysis at the 9p21 locus to test whether haplotypes at distinct linkage disequilibrium blocks predict these phenotypes. Methods and results: Using 24 single-nucleotide polymorphisms genotyped in white patients without diabetes mellitus, we reconstructed haplotypes at the 9p21 locus. Patients with angiograhic CAD/MI had ≥1 epicardial stenosis >50% (n=2352), whereas controls were asymptomatic and over the age of 60 years (n=2116). For CAD patients, regression models examined the association of haplotypes with initial age of symptomatic CAD, number of diseased vessels, and history of MI. In the case-control study, only haplotypes at 1 block tagged by rs1333049 associated with CAD more so than MI. These haplotypes also associated with early onset of CAD (β=-0.13; P=1.37×10(-4)) and disease severity (β=0.1823; P=0.006) but not with prevalent MI among patients with CAD. In contrast, haplotypes at another block tagged by rs518394 associated with prevalent MI (β=0.239; P=2.05×10(-4)), but remarkably these are inversely associated with disease severity (β=-0.196; P=0.003). This MI association was replicated in the Cleveland Clinic GeneBank premature CAD cohort (n=1385; β=0.207; P=0.019). Conclusions: Variants/haplotypes at 2 blocks are distinguished at 9p21; those at 1 block predispose to atherosclerosis, whereas those at the other predispose to MI among patients with preexisting CAD.
    Circulation Cardiovascular Genetics 05/2013; 6(4). DOI:10.1161/CIRCGENETICS.113.000104 · 4.60 Impact Factor
  • Cell Symposia: Mitochondria: from Signaling to Disease; 05/2013
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    ABSTRACT: A paradigm shift towards biology occurred in the 1990's subsequently catalyzed by the sequencing of the human genome in 2000. The cost of DNA sequencing has gone from millions to thousands of dollars with sequencing of one's entire genome costing only $1,000. Rapid DNA sequencing is being embraced for single gene disorders, particularly for sporadic cases and those from small families. Transmission of lethal genes such as associated with Huntington's disease can, through in-vitro fertilization, avoid passing it on to one's offspring. DNA sequencing will meet the challenge of elucidating the genetic predisposition for common polygenic diseases, especially in determining the function of the novel common genetic risk variants and identifying the rare variants, which may also partially ascertain the source of the missing heritability. The challenge for DNA sequencing remains great, despite human genome sequences being 99.5% identical, the 3 million single nucleotide polymorphisms (SNPs) responsible for most of the unique features add up to 60 new mutations per person which, for 7 billion people, is 420 billion mutations. It is claimed that DNA sequencing has increased 10,000 fold while information storage and retrieval only 16 fold. The physician and health user will be challenged by the convergence of two major trends, whole genome sequencing and the storage/retrieval and integration of the data.
    Journal of the American College of Cardiology 03/2013; 61(20). DOI:10.1016/j.jacc.2012.12.054 · 16.50 Impact Factor
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    ABSTRACT: Background The 9p21.3 locus is strongly associated with the risk of coronary artery disease (CAD) and with type 2 diabetes (T2D). We investigated the association of 9p21.3 variants with severity of CAD (defined by the number of vessel diseased [VD]) in the presence and absence of T2D. Methods We tested 11 9p21.3-variants for association in a white Italian study (N = 2,908), and carried out replication in 2 independent white populations, a German study (N = 2,028) and a Canadian Study (N=950). SNP association and permutation analyses were conducted. Results We identified two 9p21.3-variants, rs4977574 (P < 4×10-4) and rs2383207 (P < 1.5×10-3) that were associated with severity of CAD in subjects without T2D. Association of rs4977574 with severity of CAD was confirmed in the Canadian Study. Results from subgroup analysis among patients with T2D showed an interaction between rs10738610 and T2D with P = 4.82×10-2. Further investigation showed that rs10738610 (P < 1.99×10-2) was found to be significantly associated with severity of CAD in subjects with T2D. Conclusions The 9p21.3 locus is significantly associated with severity of CAD. The number of associations of 9p21.3 variants with severity of CAD is variable to the presence and absence of T2D. In a CAD-susceptible region of 115 kb, there is only one variant associated with the severity of coronary vessel disease in the presence of type 2 diabetes.
    BMC Medical Genetics 01/2013; 14(1):11. DOI:10.1186/1471-2350-14-11 · 2.08 Impact Factor

Publication Stats

15k Citations
2,769.53 Total Impact Points


  • 2004–2015
    • University of Ottawa
      • • Department of Medicine
      • • Department of Biochemistry, Microbiology and Immunology
      Ottawa, Ontario, Canada
  • 2012
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2011
    • Heinrich-Heine-Universität Düsseldorf
      • German Diabetes Center
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1983–2008
    • Baylor College of Medicine
      • • Department of Medicine
      • • Section of Cardiology
      • • Department of Neurology
      Houston, Texas, United States
  • 2001
    • University of Texas Southwestern Medical Center
      • Department of Pediatrics
      Dallas, Texas, United States
  • 1991
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 1987–1989
    • Houston Methodist Hospital
      Houston, Texas, United States
    • The University of Arizona
      Tucson, Arizona, United States
    • Houston Zoo
      Houston, Texas, United States
    • Detroit Medical Center
      Detroit, Michigan, United States
  • 1988
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1985
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 1984
    • Parkland Memorial Hospital
      Dallas, Texas, United States
  • 1975–1984
    • Washington University in St. Louis
      • Division of Cardiovascular Division
      San Luis, Missouri, United States
  • 1981
    • National Institutes of Health
      베서스다, Maryland, United States
  • 1974
    • University of California, San Diego
      • Department of Medicine
      San Diego, California, United States