A Genome-Wide Scan for Carotid Artery Intima-Media Thickness

Objective: Smoking is an established risk factor for atherosclerotic disease. However, the degree of the cigarette smoking-induced damage varies from individual to individual, partly due to the between-individual difference in genetic makeup. The aim of this study was to identify genetic loci influencing the effect of cigarette smoking on carotid intima-media thickness (IMT) by performing a genome-wide association smoking-by-SNP interaction analysis. Methods and results: Genome-wide genotyping was performed using the Affymetrix SNP array 6.0 among 1,010 individuals who underwent B-mode ultrasound examination of carotid IMT from the population-based Northern Manhattan Study. Cigarette pack-years was calculated as number of years smoked multiplied by number of cigarettes smoked per day, then divided by 20. After quality control, a total of 722,379 single nucleotide polymorphisms (SNPs) were included in the final analysis. Generalized linear modeling was conducted to look for smoking-by-SNP interaction on carotid IMT while controlling for age, sex, hypertension, diabetes, dyslipidemia, body mass index, waist-to-hip ratio, and the top 3 principal components estimated to capture ancestry by EIGENSTRAT. Ten SNPs near or within 5 genes showed an interactive effect with cigarette smoking on IMT with a p value <1.0E-5. Among them, 3 SNPs (including 1 exonic splice enhancer SNP rs3751283, P=8.3E-7) are near or within regulator of chromosome condensation and BTB domain containing protein 1 (RCBTB1) gene on 13q14. Specifically, for SNP rs3751283, the mean IMT was substantially increased among CC-carriers (0.70 mm, 0.76 mm, 0.81 mm for 0, <20, and ≥20 cigarette pack-years, respectively, P=2.6E-6), slightly increased with smoking pack-years among TC-carriers (0.72 mm, 0.74 mm, 0.75 mm for 0, <20, and ≥20 cigarette pack-years, respectively, P=0.03), but very similar (0.73 mm) among TT-carriers for the three smoking groups (P=0.84). Conclusion: Our genome-wide interaction analysis reveals multiple genes, especially RCBTB1, that may modify the effect of smoking on carotid IMT. These genes will be further evaluated in our full dataset with additional genotyping. Also, larger independent studies are needed to validate these findings.

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Twenty-Five Novel Loci for Carotid Intima-Media Thickness: A Genome-Wide Association Study in >45 000 Individuals and Meta-Analysis of >100 000 Individuals

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.317007 ◽

2021 ◽

Author(s):

Ming Wai Yeung ◽

Siqi Wang ◽

Yordi J. van de Vegte ◽

Oleg Borisov ◽

Jessica van Setten ◽

...

Keyword(s):

Meta Analysis ◽

Intima Media Thickness ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Susceptibility Loci ◽

Media Thickness ◽

Genome Wide ◽

A Genome ◽

Artery Disease

Objective: Carotid artery intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. Twenty susceptibility loci for cIMT were previously identified and the identification of additional susceptibility loci furthers our knowledge on the genetic architecture underlying atherosclerosis. Approach and Results: We performed 3 genome-wide association studies in 45 185 participants from the UK Biobank study who underwent cIMT measurements and had data on minimum, mean, and maximum thickness. We replicated 15 known loci and identified 20 novel loci associated with cIMT at P <5×10 −8 . Seven novel loci ( ZNF385D , AD AMTS9 , EDNRA , HAND2 , MYOCD , ITCH/EDEM2/ matrix metalloproteinase [ MMP ] 24 , and MRTFA ) were identified in all 3 phenotypes. An additional new locus ( LOXL1 ) was identified in the meta-analysis of the 3 phenotypes. Sex interaction analysis revealed sex differences in 7 loci including a novel locus ( SYNE3 ) in males. Meta-analysis of UK Biobank data with a previous meta-analysis led to identification of three novel loci ( APOB, FIP1L1, and LOXL4 ). Transcriptome-wide association analyses implicated additional genes ARHGAP42 , NDRG4 , and KANK2 . Gene set analysis showed an enrichment in extracellular organization and the PDGF (platelet-derived growth factor) signaling pathway. We found positive genetic correlations of cIMT with coronary artery disease r g =0.21 ( P =1.4×10 -7 ), peripheral artery disease r g =0.45 ( P =5.3×10 -5 ), and systolic blood pressure r g =0.30 ( P =4.0×10 -18 ). A negative genetic correlation between average of maximum cIMT and high-density lipoprotein was found r g =−0.12 ( P =7.0×10 -4 ). Conclusions: Genome-wide association meta-analyses in >100 000 individuals identified 25 novel loci associated with cIMT providing insights into genes and tissue-specific regulatory mechanisms of proatherosclerotic processes. We found evidence for shared biological mechanisms with cardiovascular diseases.

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Intima-media thickness measurement of the carotid artery in patients with primary hyperparathyroidism

Endocrine Abstracts ◽

10.1530/endoabs.37.ep617 ◽

2015 ◽

Author(s):

Dilek Tuzun ◽

Ayten Oguz ◽

Murat Sahin ◽

Safa Ersen Ganidagli ◽

Didem Atay ◽

...

Keyword(s):

Carotid Artery ◽

Primary Hyperparathyroidism ◽

Intima Media Thickness ◽

Thickness Measurement ◽

Media Thickness

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QT Intervals Correlate with Carotid Artery Intima Media Thickness in a Gender-Specific and Segment-Specific Manner in Asymptomatic Dyslipidemic Patients

Cardiology & Neurocardiovascular Diseases ◽

10.24966/cncd-8860/100005 ◽

2015 ◽

Vol 2 (1) ◽

pp. 1-5

Author(s):

Giuliana Mombelli ◽

Keyword(s):

Carotid Artery ◽

Intima Media Thickness ◽

Media Thickness ◽

Qt Intervals ◽

Specific Manner ◽

Gender Specific

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Application of the Measurement of Carotid Intima-Media Thickness for Prediction of the Essential Hypertension in Children

Revista de Chimie ◽

10.37358/rc.18.6.6366 ◽

2018 ◽

Vol 69 (6) ◽

pp. 1550-1553

Author(s):

Rosana Manea ◽

Bianca Elena Popovici ◽

Carmen Daniela Neculoiu ◽

Dan Minea ◽

Alina Calin

Keyword(s):

Blood Pressure ◽

Essential Hypertension ◽

Carotid Artery ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Diagnostic Methods ◽

Control Group ◽

Study Group ◽

Media Thickness ◽

Hypertension In Children

Hypertension is a major risk factor for progression of the atherosclerotic process and for developing of degenerative cardiovascular diseases in adulthood. The aim of this study is to evaluate how the measurement of carotid intima - media thickness for prediction of essential hypertension in children can be used.The study group included 81 children and the control group 61 children, all aged between 5 - 17 years and 11 months old, and admitted in Children Hospital Brasov in the period of 2009 � 2014. The study protocol included: BMI, blood pressure and Doppler echography of the common carotid artery for each group. Mean age of the patients from the study group was 13.67 years, 43.20 % girls and 56.80 % boys, while in the control group, the mean age was 14.07 years, 54.10% girls and 45.90 % boys. 70.37% of the children from the study group presented obesity, while in the control group 40.98% were obese. The IMTC study group ranged from 0.52 - 0.69 mm and the limits of the normotensive subjects were 0.32 -0.54 mm. In both groups the obese patients were found to have increased carotid artery intima-media, which means that IMTC was positively correlated with BMI (p=0.000001).It is necessary to identify diagnostic methods easily applicable for children, allowing involvement of the characteristics of the arterial wall in the degenerative pathological processes. Increased intima-media ratio is positively correlated with high values of blood pressure.

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