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Published on: November 17, 2018
HDL cholesterol as a mediator of the relationship between breastfeeding and coronary atherosclerosis from a two-step
Baoquan Zhang1, Bin Yang2, Wenlong Xiu2
1Department of Neonatology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, China. zbq2701@fjmu.edu.cn.
Insights
Breastfeeding is linked to a lower risk of coronary atherosclerosis (CA). This protective effect may be partly mediated by increased high-density lipoprotein cholesterol (HDL-C) levels.
Area of Science:
- Cardiovascular Epidemiology
- Genetics
- Public Health
Background:
- The relationship between breastfeeding and coronary atherosclerosis (CA) remains debated.
- Investigating early-life factors like breastfeeding is crucial for understanding cardiovascular disease (CVD) etiology.
- Mendelian randomization (MR) offers a robust method to explore causal links between exposures and outcomes.
Purpose of the Study:
- To investigate the causal association between breastfeeding and coronary atherosclerosis (CA) using Mendelian randomization (MR).
- To identify potential mediating factors, such as lipid profiles, that explain the link between breastfeeding and CA.
- To evaluate the role of high-density lipoprotein cholesterol (HDL-C) as a mediator in this association.
Main Methods:
- Utilized two independent European adult cohorts for discovery and replication analyses.
- Employed summary statistics from large genome-wide association studies (GWAS) for CA and breastfeeding phenotypes.
- Conducted two-step MR analysis to assess the mediating effect of candidate variables, including HDL-C.
Main Results:
- MR analysis revealed a significant protective association between breastfeeding and reduced risk of CA in both discovery (OR: 0.826) and replication (OR: 0.439) datasets.
- High-density lipoprotein cholesterol (HDL-C) was identified as a significant mediator, explaining 10.26% of the total effect.
- The findings suggest that breastfeeding confers a protective effect against CA, partly through elevated HDL-C levels.
Conclusions:
- Breastfeeding demonstrates a causal protective effect against coronary atherosclerosis.
- Increased HDL-C levels represent a key mediating pathway for the cardioprotective benefits of breastfeeding.
- Promoting breastfeeding could be a valuable early-life intervention strategy for long-term cardiovascular health.
Abstract:
The association between breastfeeding and coronary atherosclerosis (CA) is still controversial. In this study, we employed Mendelian randomization (MR) analysis to inverstigate the association between breastfeeding and CA, and to identify potential mediators underlying this link. Breastfeeding status was determined via a recall-based questionnaire assessing whether individuals had been breastfed in infancy. Two independent datasets were selected, a discovery dataset from GWAS catalog (GCST90041823, 247,160 cases and 99,661 controls), and a replication dataset from Neale Lab (193,838 cases and 273,743 controls). CA was defined based on related diseases phenotypes, with summary statistics obtained from the FinnGen, including 56,685 cases and 378,019 controls. Nine variables were selected as candidate mediators. All data were obtained from European adult cohorts. MR was employed to estimate the causal effect of breastfeeding on CA. To explore potential pathways, a two-step MR analysis was used to assess the mediating roles of candidate variables. MR analysis supported a causal association between breastfeeding and reduced risk of CA, both in discovery (OR: 0.826, 95%CI: 0.724-0.941, p = 0.004) and replication dataset (OR: 0.439, 95%CI: 0.274-0.703, p = 0.0006). High-density lipoprotein cholesterol (HDL-C) was identified as a potential mediator, accounting for 10.26% of the total effect, 95% CI 1.4-19.13%. Breastfeeding exerted a protective effect against CA, in part via increased HDL-C levels, highlighting a potential early-life intervention target for cardiovascular health.
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