| Title: | Effects of blood lead on coronary artery disease and its risk factors: a Mendelian Randomization study |
| Journal: | Scientific Reports |
| Published: | 5 Nov 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31690775/ |
| DOI: | https://doi.org/10.1038/s41598-019-52482-1 |
| URL: | https://www.nature.com/articles/s41598-019-52482-1.pdf |
| Citations: | 9 (5 in last 2 years) as of 8 Aug 2024 |
Publication 4755
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Abstract
Lead is pervasive, although lead exposure has fallen in response to public health efforts. Observationally, lead is positively associated with cardiovascular disease and hypertension. We used separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization) based on 13 single nucleotide polymorphisms (SNP), from a genome wide association study, strongly (p-value < 5 × 10−6) and independently associated with blood lead. These SNPs were applied to a large extensively genotyped coronary artery disease (CAD) study (cases = <76014, controls = <264785) largely based on CARDIoGRAPMplusC4D 1000 Genomes and the UK Biobank SOFT CAD, to the UK Biobank (n = 361,194) for blood pressure and to the DIAGRAM 1000 genomes diabetes case (n = 26,676)-control (n = 132,532) study. SNP-specific Wald estimates were combined using inverse variance weighting, MR-Egger and MR-PRESSO. Genetically instrumented blood lead was not associated with CAD (odds ratio (OR) 1.01 per effect size of log transformed blood lead, 95% confidence interval (CI) 0.97, 1.05), blood pressure (systolic −0.18 mmHg, 95% CI −0.44 to 0.08 and diastolic −0.03 mmHg, 95% CI −0.09 to 0.15) or diabetes (OR 0.98, 95% CI 0.92 to 1.03) using MR-PRESSO estimates corrected for an outlier SNP (rs550057) from the highly pleiotropic gene ABO. Exogenous lead may have different effects from endogenous lead; nevertheless, this study raises questions about the role of blood lead in CAD.</p>
3 Authors
- C. Mary Schooling
- Glen D. Johnson
- Jean Grassman
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