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PLoS One. 2019;14(3):e0214370.

Genome-wide association study of coronary artery calcification in asymptomatic Korean populations.

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제1저자 최수연 · 교신저자 최수연, 최승호

소속 (5)
  1. Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
  2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  3. DNA Link, Inc., Seoul, Korea.
  4. Department of Surgery, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
  5. Department of Public Health Science, Seoul National University, Seoul, Korea.

Abstract

Epidemiologic evidence indicates that the prevalence and severity of coronary artery disease vary depending on ethnicity. In this study, a genome-wide association study for coronary artery calcification (CAC) was performed in a Korean population-based sample of 400 subjects without prior coronary artery disease and replicated in another of 1,288 subjects. CAC score, as assessed by multi-detector computed tomography, was evaluated in volunteers for screening purposes as part of a routine health examination. CAC score greater than the 90th percentile across the age in each sex group was considered severe CAC. Single nucleotide polymorphisms (SNPs) associated with severe CAC after adjusting for age, sex, hypertension, and diabetes were investigated using the additive model of logistic regression. One SNP (rs10757272 in the intronic region of the CDKN2B-AS1 gene in chromosome 9p21.3) met Bonferroni correction in the discovery set (p = 7.55E-08) and was also significant in the validation set by TaqMan assay (p = 0.036). Subjects with rs10757272 were found to have an increased odds ratio (OR) of having severe CAC in multivariate logistic regression analysis after adjusting for age, sex, hypertension, and diabetes (adjusted OR 3.24 and 95% CI 2.11-4.97). In conclusion, SNP rs10757272 in chromosome 9p21.3 was associated with severe CAC based on age and sex in an asymptomatic community-based Korean population. Therefore, it was associated with promotion of coronary artery calcification in subclinical state.

Figures

Fig 1
Fig 1 Manhattan plot of genome-wide association signals with severe coronary artery calcification (A) and a quantile–quantile plot (B) in the discovery set. In the Manhattan plot, the x-axis represents the SNP markers on each chromosome. The y-axis shows the -log10 p-value (logistic regression). The red horizontal line represents the genome-wide significance threshold p = 9.078E-08, and the blue horizontal line represents the genome-wide suggestiveness threshold p = 1E-04.
Fig 2
Fig 2 Regional association plot in chromosomes 9. The purple diamonds indicate the associated SNP according to joint analyses. Nearby SNPs are color-coded according to the level of linkage disequilibrium with the top SNP. The left y-axis shows the significance of the association on a -log10 p-value (logistic regression), and the right y-axis shows the recombination rate across the region. Estimated recombination rates from the 1000 Genomes Project Asian base data and hg19 database [19] are plotted with the blue line to reflect the local linkage disequilibrium structure.

그림 출처: PubMed Central 공개 논문 (PMC6438465)

Conflict of interest statement

Eunsoon Shin and Jong-Eun Lee are employed by DNA Link, Inc. DNA Link, Inc. provided support in the form of salaries for authors ES and J-EL. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
PloS one · eISSN 1932-6203
전자 출판
2019-03-28
MeSH
Adult · Asian People / genetics · Coronary Vessels / diagnostic imaging / pathology · Female · Genome-Wide Association Study* · Genotype · Humans · Logistic Models · Male · Middle Aged · Odds Ratio · Polymorphism, Single Nucleotide · RNA, Long Noncoding / genetics · Republic of Korea · Retrospective Studies · Severity of Illness Index · Tomography, X-Ray Computed · Vascular Calcification / genetics / pathology
Substances
CDKN2B antisense RNA, human · RNA, Long Noncoding
데이터
figshare: 10.6084/m9.figshare.7850981
참고문헌
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