scholarly journals Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0185663 ◽  
Author(s):  
Bendik S. Winsvold ◽  
Francesco Bettella ◽  
Aree Witoelar ◽  
Verneri Anttila ◽  
Padhraig Gormley ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Risk ◽  
Common Variants ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Artery Disease ◽  
Shared Genetic

Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease

2020 ◽  
Vol 52 (11) ◽  
pp. 1169-1177 ◽  
Author(s):  
Satoshi Koyama ◽  
Kaoru Ito ◽  
Chikashi Terao ◽  
Masato Akiyama ◽  
Momoko Horikoshi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Risk ◽  
Genome Wide ◽  
Artery Disease ◽  
Shared Genetic

Abstract 447: Deep Transcriptomic Analysis of Human Vascular Cells Identifies Risk Genes for Common Vascular Diseases

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Sylvia T Nurnberg ◽  
YoSon Park ◽  
Jordi Vaquero-Garcia ◽  
Milos Pjanic ◽  
Susanna Elwyn ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Susceptibility ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Allele Specific ◽  
Artery Disease ◽  
Shared Genetic

The most recent Genome-wide Association Study (GWAS) meta-analysis has reported a total of 58 genomic loci to be statistically significantly associated with genetic susceptibility to Coronary Artery Disease (CAD) (Consortium, 2015). Many of these loci also associate with other phenotypes, with the majority being lipid traits (Tada et al., 2014). But also hypertension, stroke (Dichgans et al., 2014) and migraine (Pickrell et al., 2016) appear to share genetic determinants with CAD. To functionally annotate the genomic loci harboring these association SNPs we sequenced the transcriptomes of 20 same donor human coronary artery endothelial (EC) and smooth muscle cell (SMC) lines. Deep RNA-Sequencing was used to assess Differential Gene Expression, Differential Splicing and Allele-Specific Expression. Focusing on GWAS loci for vascular phenotypes (CAD, stroke, migraine) we identified genes which display allele-specific differences in mRNA expression or splicing. We propose these genes as suitable targets for follow up studies. Consortium, C.A.D. (2015). A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nature genetics 47, 1121-1130. Tada, H., Won, H.H., Melander, O., Yang, J., Peloso, G.M., and Kathiresan, S. (2014). Multiple associated variants increase the heritability explained for plasma lipids and coronary artery disease. Circulation Cardiovascular genetics 7, 583-587. Dichgans, M., Malik, R., Konig, I.R., Rosand, J., Clarke, R., Gretarsdottir, S., Thorleifsson, G., Mitchell, B.D., Assimes, T.L., Levi, C., et al. (2014). Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. Stroke; a journal of cerebral circulation 45, 24-36. Pickrell, J.K., Berisa, T., Liu, J.Z., Segurel, L., Tung, J.Y., and Hinds, D.A. (2016). Detection and interpretation of shared genetic influences on 42 human traits. Nature genetics 48, 709-717.

scholarly journals Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

2020 ◽  
Vol 76 (6) ◽  
pp. 703-714 ◽  
Author(s):  
Minxian Wang ◽  
Ramesh Menon ◽  
Sanghamitra Mishra ◽  
Aniruddh P. Patel ◽  
Mark Chaffin ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
South Asians ◽  
Polygenic Score ◽  
Genome Wide ◽  
A Genome ◽  
Artery Disease

4259Discovery of the first genome-wide significant risk loci for syncope and collapse

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Ahlberg ◽  
K Hadji-Turdeghal ◽  
L Andreasen ◽  
C M Hagen ◽  
J Ghouse ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cerebral Arteries ◽  
European Ancestry ◽  
Carrier Status ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Artery Disease ◽  
The Brain

Abstract Background Syncope is a common condition in the general population causing frequent hospitalisation and visits to the emergency department. Family aggregation and twin studies have previously indicated that syncope and collapse has a heritable component. Purpose We investigated whether common genetic variants predispose to syncope and collapse. Methods We used genome-wide association data on syncope and collapse for 408,961 individuals with European ancestry from the UK Biobank study. In a replication study, the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n=86,189) was used to investigate the risk of incident syncope stratified by genotype carrier status. Results We report on a genome-wide significant locus on chromosome 2q32.1 with the lead SNP rs12465214 (odds ratio [OR] = 1.13, 95% confidence interval [CI] = 1.10–1.17, P=5.8x10–15; Figure 1a). This association was replicated in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (HR=1.30, CI: 1.15–1.46, P=1.68x10–5; Figure 1b). LD score regression demonstrated a significant genetic correlation (rg) with coronary artery disease (rg=0.41, P=6.99x10–15) and related phenotypes such as angina and hypertension (Figure 1c). Analyses of eQTL (P=4x10–8) and epigenetic chromatin states revealed that variation in this locus likely affects expression of the gene ZNF804A, which resides in its proximity (Figure 1d). A qPCR analysis showed that ZNF804A was mostly expressed in the brain. A lower level of ZNF804A expression was also detected in the cerebral arteries. ZNF804A was not expressed in heart tissue. Figure 1 Conclusion rs12465214 is associated with syncope and collapse. Variation in this locus likely modulates the expression of the nearby gene ZNF804A through eQTLs and chromatin interactions. ZNF804A is mainly expressed in the brain and cerebral arteries. However, the precise function of ZNF804A is unknown. Furthermore, syncope and collapse is a polygenetic trait and share a significant genetic overlap with coronary artery disease, angina and hypertension. Acknowledgement/Funding This work was supported by grants from The John and Birthe Meyer Foundation, The Research Foundation of the Heart Centre, Rigshospitalet, The Research

scholarly journals Polygenic risk for coronary artery disease in the Scottish and English population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuhua Yang ◽  
Fabian Starnecker ◽  
Shichao Pang ◽  
Zhifen Chen ◽  
Ulrich Güldener ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Individual Risk ◽  
Risk Alleles ◽  
Genome Wide ◽  
Artery Disease ◽  
Cad Risk

Abstract Background Epidemiological studies have repeatedly observed a markedly higher risk for coronary artery disease (CAD) in Scotland as compared to England. Up to now, it is unclear whether environmental or genetic factors might explain this phenomenon. Methods Using UK Biobank (UKB) data, we assessed CAD risk, based on the Framingham risk score (FRS) and common genetic variants, to explore the respective contribution to CAD prevalence in Scotland (n = 31,963) and England (n = 317,889). We calculated FRS based on sex, age, body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), antihypertensive medication, smoking status, and diabetes. We determined the allele frequency of published genome-wide significant risk CAD alleles and a weighted genetic risk score (wGRS) for quantifying genetic CAD risk. Results Prevalence of CAD was 16% higher in Scotland as compared to England (8.98% vs. 7.68%, P < 0.001). However, the FRS only predicted a marginally higher CAD risk (less than 1%) in Scotland (12.5 ± 10.5 vs.12.6 ± 10.6, P = 0.03). Likewise, the overall number of genome-wide significant variants affecting CAD risk (157.6 ± 7.7 and 157.5 ± 7.7; P = 0.12) and a wGRS for CAD (2.49 ± 0.25 in both populations, P = 0.14) were remarkably similar in the English and Scottish population. Interestingly, we observed substantial differences in the allele frequencies of individual risk variants. Of the previously described 163 genome-wide significant variants studied here, 35 variants had higher frequencies in Scotland, whereas 37 had higher frequencies in England (P < 0.001 each). Conclusions Neither the traditional risk factors included in the FRS nor a genetic risk score (GRS) based on established common risk alleles explained the higher CAD prevalence in Scotland. However, we observed marked differences in the distribution of individual risk alleles, which emphasizes that even geographically and ethnically closely related populations may display relevant differences in the genetic architecture of a common disease.

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