A large-scale exome array analysis of venous thromboembolism
Sara Lindström1,2, Jennifer A Brody3, Constance Turman4
1Department of Epidemiology, University of Washington, Seattle, Washington.
Genetic Epidemiology
|January 20, 2019
Summary
This study searched for low-frequency genetic variants linked to venous thromboembolism (VTE) risk. No new significant associations were found, suggesting larger studies are needed to uncover rare VTE risk factors.
Area of Science:
- Genetics
- Cardiovascular Disease Research
Background:
- Genome-Wide Association Studies (GWAS) have identified common variants associated with venous thromboembolism (VTE).
- A comprehensive exome-wide search for low-frequency variants impacting VTE risk has been lacking.
Purpose of the Study:
- To conduct a meta-analysis of exome-wide studies to identify low-frequency variants associated with VTE risk.
- To perform single variant and gene-based rare variant tests.
Main Methods:
- Meta-analysis of 11 studies with 8,332 VTE cases and 16,087 controls (European ancestry) and 382 cases and 1,476 controls (African American ancestry).
- Genotyping using the Illumina HumanExome BeadChip.
- Analysis using the seqMeta package in R for single variant and gene-based rare variant tests.
- Focus on variants with at least 40 minor alleles across studies (MAF ~0.08%).
Main Results:
- Confirmed associations with known VTE loci: ABO, F5, F11, and FGA.
- No novel significant findings were observed in single variant or gene-based analyses after adjusting for multiple testing.
- The study had >80% power to detect odds ratios >1.5 for variants with MAF of 0.01 and >1.8 for MAF of 0.005.
Conclusions:
- This exome-wide meta-analysis did not identify novel low-frequency variants associated with VTE risk.
- Larger sample sizes and whole-genome sequence data may be required to discover rare variants influencing VTE susceptibility.
Related Concept Videos
02:41pH Scale
79.7K
Hydronium and hydroxide ions are present both in pure water and in all aqueous solutions, and their concentrations are inversely proportional as determined by the ion product of water (Kw). The concentrations of these ions in a solution are often critical determinants of the solution’s properties and the chemical behaviors of its other solutes. Two different solutions can differ in their hydronium or hydroxide ion concentrations by a million, billion, or even trillion times. A common means of...
79.7K
01:04Venous Return
12.3K
The circulatory system plays a crucial role in ensuring the optimal functioning of the human body. One of its critical components is venous return - the process that completes the blood circulation cycle. This article will delve into the concept of venous return, how it works, and its significance to our health.
What is Venous Return?
Venous return refers to the rate at which blood flows back to the heart from the body's peripheral veins. It's an integral part of the circulatory system...
What is Venous Return?
Venous return refers to the rate at which blood flows back to the heart from the body's peripheral veins. It's an integral part of the circulatory system...
12.3K
01:30Venous Thrombosis I: Introduction
462
Venous thrombosis, the most common disorder of the veins, involves the formation of a thrombus or blood clot associated with vein inflammation. It can be classified as either superficial vein thrombosis or deep vein thrombosis.Superficial Vein Thrombosis: This involves the formation of a thrombus in a superficial vein, usually the greater or lesser saphenous vein. Though less severe than deep vein thrombosis (DVT), SVT can lead to complications if untreated.Deep Vein Thrombosis (DVT): This...
462
01:26Scaling
593
In designing and analyzing filters, resonant circuits, or circuit analysis at large, working with standard element values like 1 ohm, 1 henry, or 1 farad can be convenient before scaling these values to more realistic figures. This approach is widely utilized by not employing realistic element values in numerous examples and problems; it simplifies mastering circuit analysis through convenient component values. The complexity of calculations is thereby reduced, with the understanding that...
593
01:29Venous Thrombosis III: Interprofessional Care
365
Venous thrombosis requires effective prevention and treatment strategies to improve patient outcomes and reduce potential complications.Prevention StrategiesHealthcare providers must prioritize preventing venous thromboembolism (VTE) for all adult patients upon admission. Interventions depend on bleeding and thrombosis risk, medical history, current medications, diagnoses, planned procedures, and patient preferences. Patients on bed rest should change positions every two hours and, if not...
365
01:30Venous Thrombosis IV: Nursing Management
263
Nursing management begins with a thorough assessment of the patient's health history. Key factors include trauma to veins, peripherally inserted central catheters, varicose veins, recent pregnancy or childbirth, surgery, bacteremia, prolonged bed rest, atrial fibrillation, COPD, heart failure, cancer, coagulation disorders, myocardial infarction, spinal cord injury, stroke, prolonged travel, recent bone fractures, and dehydration. Review medication intake, particularly oral contraceptives,...
263