Using genetics to detangle the relationships between red cell distribution width and cardiovascular diseases: a unique role for body mass index.

Abstract

OBJECTIVE:

Red cell distribution width (RDW) is an enigmatic biomarker associated with the presence and severity of multiple cardiovascular diseases (CVDs). It is unclear whether elevated RDW contributes to, results from, or is pleiotropically related to CVDs. We used contemporary genetic techniques to probe for evidence of aetiological associations between RDW, CVDs, and CVD risk factors.

METHODS:

Using an electronic health record (EHR)-based cohort, we built and deployed a genetic risk score (GRS) for RDW to test for shared genetic architecture between RDW and the cardiovascular phenome. We also created GRSs for common CVDs (coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, venous thromboembolism) and CVD risk factors (body mass index (BMI), low-density lipoprotein, high-density lipoprotein, systolic blood pressure, diastolic blood pressure, serum triglycerides, estimated glomerular filtration rate, diabetes mellitus) to test each for association with RDW. Significant GRS associations were further interrogated by two-sample Mendelian randomisation (MR). In a separate EHR-based cohort, RDW values from 1-year pre-gastric bypass surgery and 1-2 years post-gastric bypass surgery were compared.

RESULTS:

In a cohort of 17 937 subjects, there were no significant associations between the RDW GRS and CVDs. Of the CVDs and CVD risk factors, only genetically predicted BMI was associated with RDW. In subsequent analyses, BMI was associated with RDW by multiple MR methods. In subjects undergoing bariatric surgery, RDW decreased postsurgery and followed a linear relationship with BMI change.

CONCLUSIONS:

RDW is unlikely to be aetiologically upstream or downstream of CVDs or CVD risk factors except for BMI. Genetic and clinical association analyses support an aetiological relationship between BMI and RDW.

• Authors: Timothy E Thayer, Shi Huang, Eric Farber-Eger, Joshua A Beckman, Evan L Brittain, Jonathan D Mosley, Quinn S Wells
• Journal: Open heart (Open Heart) Vol. 8 Issue 2 (09 2021) ISSN: 2053-3624 [Print] England
• PMID: 34521746 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Biomarkers
• Genetic Markers

Topics

• Biomarkers (blood)
• Body Mass Index
• Cardiovascular Diseases (blood, ethnology, genetics)
• Erythrocyte Indices
• Ethnicity
• Female
• Genetic Markers (genetics)
• Humans
• Incidence
• Male
• Mendelian Randomization Analysis (methods)
• Middle Aged
• Phenomics (methods)
• Risk Assessment (methods)
• United States (epidemiology)