Addressing the complexity of cardiovascular disease by design

Lotta, Luca A.; Peyvandi, Flora

doi:10.1016/s0140-6736(10)62240-4

Cited by 9 publications

(10 citation statements)

References 6 publications

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“…Genome-wide association studies (GWAS) have identified numerous loci associated with complex phenotypes and disease traits, such as coronary heart disease (Lotta and Peyvandi 2011; Schunkert et al 2011), blood pressure (Ehret et al 2011; Levy et al 2009; Newton-Cheh et al 2009), lipids (Teslovich et al 2010), body mass index (Guo et al 2013; Monda et al 2013; Speliotes et al 2010), and type 2 diabetes (Morris et al 2012; Voight et al 2010). Although GWAS have provided valuable insights into the genetic basis of complex traits, they explain only a small proportion of the heritability of most traits (Tenesa and Haley 2013).…”

Section: Introductionmentioning

confidence: 99%

A systematic heritability analysis of the human whole blood transcriptome

et al. 2015

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Genome-wide expression quantitative trait locus (eQTL) mapping may reveal common genetic variants regulating gene expression. In addition to mapping eQTLs, we systematically evaluated the heritability of the whole blood transcriptome in 5626 participants from the Framingham Heart Study. Of all gene expression measurements, about 40% exhibit evidence of being heritable (hgeneExp2>0, (p<0.05]), the average heritability was estimated to be 0.13, and 10% display hgeneExp2>0.2. In order to identify the role of eQTLs in promoting phenotype differences and disease susceptibility, we investigated the proportion of cis/trans eQTLs in different heritability categories and discovered that genes with higher heritability are more likely to have cis eQTLs that explain large proportions of variance in the expression of the corresponding genes. Single cis eQTLs explain 0.33–0.53 of variance in transcripts on average, whereas single trans eQTLs only explain 0.02–0.07. The top cis eQTLs tend to explain more variance in the corresponding gene when its hgeneExp2 is greater. Taking body mass index (BMI) as a case study, we cross-linked cis/trans eQTLs with both GWAS SNPs and differentially expressed genes for BMI. We discovered that BMI GWAS SNPs in 16p11.2 (e.g., rs7359397) are associated with several BMI differentially expressed genes in a cis manner (e.g. SULT1A1, SPNS1, and TUFM). These BMI signature genes explain a much larger proportion of variance in BMI than do the GWAS SNPs. Our results shed light the impact of eQTLs on the heritability of the human whole blood transcriptome and its relations to phenotype differences.

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Section: Introductionmentioning

confidence: 99%

A systematic heritability analysis of the human whole blood transcriptome

et al. 2015

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“…3,4,26 The result accords with a more recent study that the pathogenesis of MI and coronary atherosclerosis is due to different genetic variants. 27,28 Based on this conclusion, we conducted this meta-analysis to obtain a competitive result via combining more eligible studies, enlarging the sample size, and performing a subgroup analysis. No associations were detected between the AGT M235T polymorphism and MI risk in the overall population; the finding was consistent with those from the previous meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

The M235T polymorphism in the angiotensinogen gene and myocardial infarction risk: A meta-analysis

Wang

Pan

2013

J Renin Angiotensin Aldosterone Syst

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Coronary artery disease (CAD) arises as a complex-trait disease that includes myocardial infarction (MI) and coronary atherosclerosis; the role of genetic and environmental risk factors promotes the development of the disorder. The classic risk factors include family history, body mass index, smoking habits, hypertension, diabetes mellitus and serum lipid levels. In addition, genetic factors also play important roles in the pathogenesis of CAD. It has been estimated that approximately 50% of the variability of the major risk factors for CAD is determined by genetics. 1 Over the past few years, the role of the renin-angiotensin-aldosterone system (RAAS) in the development of MI has generated much interest across the world. The investigations were expanded to implicate that the RAAS in a variety of physiologic processes may play a significant role in the initiation and progression of atherosclerosis. 2 To date, more and more studies show that the angiotensinogen (AGT, the components of RAAS) gene M235T polymorphism is closely associated with MI among different populations. The AGT M235T single nucleotide polymorphism (SNP) is a methionine (Met) to threonine (Thr) amino acid substitution at codon 235, designated the M and T alleles, respectively. However, published results have been inconsistent. 3,4 To help clarify the inconsistent findings, with the publication of several more recent studies we conducted this meta-analysis of the M235T polymorphism in the AGT gene and risk of MI. This meta-analysis includes 21 studies with a total of 5887 MI cases and 6164 controls. Materials and methods Literature and search strategyAll studies published before December 2011 on MI and the AGT M235T polymorphism were sought by computerbased searches of Google Scholar, PubMed, CochraneThe M235T polymorphism in the angiotensinogen gene and myocardial infarction risk: A meta-analysis Yu-Jing Wang 1 and Yan Pan 2 Abstract Objective: The angiotensinogen (AGT) gene M235T polymorphism has been reported to be associated with myocardial infarction (MI), but previous studies have been inconsistent. The present study aimed at assessing the association of M235T polymorphism in the AGT gene with MI using a meta-analysis. Methods: We retrieved literature in Google Scholar, PubMed, Cochrane Library and the China National Knowledge Infrastructure database (January 1990-December 2011 for the relevant studies on the AGT polymorphism M235T and risk of MI. Statistical analyses were carried out using Stata 10.0 for combining all the relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Begg's test was used to measure publication bias. Results: A total of 21 case-control studies containing 5887 patients and 6164 controls were enrolled into this meta-analysis. Overall, significant association was found between the AGT gene M235T polymorphism and risk of MI in the subgroup analysis for TT vs MT in Asians (OR 1.47, 95% CI: 1.01-2.12; p = 0.04). No associations were detected between AG...

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“…В настоящее время активно изучается прогности-ческая значимость полиморфизмов генов, кодирующих различные классы белков, участвующих в патогенезе ате-росклероза (аполипопротеины, кинезины, интегрины, фак-торы воспаления и т.д.) [2,3]. Учитывая тесную взаимосвязь процессов атерогенеза и тромбообразования, особое вни-мание привлекает полиморфизм генов системы гемостаза.…”

Section: Methodsunclassified

“…Detection of gene polymorphisms probably associated with atherothrombosis will certainly be useful in cardiovascular risk estimation. Prognostic value of gene polymorphisms, which encode different classes of proteins involved in atherosclerosis pathogenesis (apolipoproteins, kinesins, integrins, inflammatory factors and others) is actively studied now [2,3]. Considering close correlation between atherogenesis and thrombogenesis processes it is important to study polymorphisms of haemostatic system genes.…”

Section: генетические предикторы прогноза при ибсmentioning

confidence: 99%