دورية أكاديمية
أعرض في EDS

Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease.

التفاصيل البيبلوغرافية
العنوان: Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease.
المؤلفون: Musameh MD; Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom., Wang WY; School of Medicine, University of Queensland, Brisbane, Queensland, Australia., Nelson CP; Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom., Lluís-Ganella C; Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain., Debiec R; Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom., Subirana I; Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain; Epidemiology and Public Health Network (CIBERESP), Barcelona, Spain., Elosua R; Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain., Balmforth AJ; Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds, United Kingdom., Ball SG; University of Leeds, MCRC, Leeds Institute of Genetics, Health and Therapeutics, Leeds, United Kingdom., Hall AS; Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds, United Kingdom., Kathiresan S; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America., Thompson JR; Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom., Lucas G; Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain., Samani NJ; Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom., Tomaszewski M; Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
المصدر: PloS one [PLoS One] 2015 Feb 06; Vol. 10 (2), pp. e0117684. Date of Electronic Publication: 2015 Feb 06 (Print Publication: 2015).
نوع المنشور: Clinical Trial; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Epistasis, Genetic* , Polymorphism, Single Nucleotide*, Coronary Artery Disease/*genetics, Adult ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; United Kingdom
مستخلص: Objective: Only a small fraction of coronary artery disease (CAD) heritability has been explained by common variants identified to date. Interactions between genes of importance to cardiovascular regulation may account for some of the missing heritability of CAD. This study aimed to investigate the role of gene-gene interactions in common variants in candidate cardiovascular genes in CAD.
Approach and Results: 2,101 patients with CAD from the British Heart Foundation Family Heart Study and 2,426 CAD-free controls were included in the discovery cohort. All subjects were genotyped with the Illumina HumanCVD BeadChip enriched for genes and pathways relevant to the cardiovascular system and disease. The primary analysis in the discovery cohort examined pairwise interactions among 913 common (minor allele frequency >0.1) independent single nucleotide polymorphisms (SNPs) with at least nominal association with CAD in single locus analysis. A secondary exploratory interaction analysis was performed among all 11,332 independent common SNPs surviving quality control criteria. Replication analyses were conducted in 2,967 patients and 3,075 controls from the Myocardial Infarction Genetics Consortium. None of the interactions amongst 913 SNPs analysed in the primary analysis was statistically significant after correction for multiple testing (required P<1.2x10-7). Similarly, none of the pairwise gene-gene interactions in the secondary analysis reached statistical significance after correction for multiple testing (required P = 7.8x10-10). None of 36 suggestive interactions from the primary analysis or 31 interactions from the secondary analysis was significant in the replication cohort. Our study had 80% power to detect odds ratios > 1.7 for common variants in the primary analysis.
Conclusions: Moderately large additive interactions between common SNPs in genes relevant to cardiovascular disease do not appear to play a major role in genetic predisposition to CAD. The role of genetic interactions amongst less common SNPs and with medium and small magnitude effects remain to be investigated.
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; MR/L01629X/1 United Kingdom MRC_ Medical Research Council; R01 HL087676 United States HL NHLBI NIH HHS; 085475 United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Note: Original DateCompleted: 20150210
تواريخ الأحداث: Date Created: 20150207 Date Completed: 20150330 Latest Revision: 20220129
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4320092
DOI: 10.1371/journal.pone.0117684
PMID: 25658981
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0117684