| Title: | Comprehensive Investigation of Circulating Biomarkers and Their Causal Role in Atherosclerosis-Related Risk Factors and Clinical Events |
| Journal: | Circulation Genomic and Precision Medicine |
| Published: | 30 Oct 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33125266/ |
| DOI: | https://doi.org/10.1161/circgen.120.002996 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.120.002996 |
| Citations: | 20 (12 in last 2 years) as of 8 Aug 2024 |
Publication 4590
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Abstract
BACKGROUND: Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood.</p>
METHODS: We performed multivariable-adjusted regressions and 2-sample Mendelian randomization analyses to assess observational and causal associations of 27 circulating biomarkers with 7 cardiovascular traits in up to 451 933 participants of the UK Biobank.</p>
RESULTS: After multiple-testing correction (alpha=1.3×10-4), we found a total of 15, 9, 21, 22, 26, 24, and 26 biomarkers strongly associated with coronary artery disease, ischemic stroke, atrial fibrillation, type 2 diabetes, systolic blood pressure, body mass index, and waist-to-hip ratio; respectively. The Mendelian randomization analyses confirmed strong evidence of previously suggested causal associations for several glucose- and lipid-related biomarkers with type 2 diabetes and coronary artery disease. Particularly interesting findings included a protective role of IGF-1 (insulin-like growth factor 1) in systolic blood pressure, and the strong causal association of lipoprotein(a) in coronary artery disease development (β, -0.13; per SD change in exposure and outcome and odds ratio, 1.28; P=2.6×10-4 and P=7.4×10-35, respectively). In addition, our results indicated a causal role of increased ALT (alanine aminotransferase) in the development of type 2 diabetes and hypertension (odds ratio, 1.59 and β, 0.06, per SD change in exposure and outcome; P=4.8×10-11 and P=6.0×10-5). Our results suggest that it is unlikely that CRP (C-reactive protein) and vitamin D play causal roles of any meaningful magnitude in development of cardiometabolic disease.</p>
CONCLUSIONS: We confirmed and extended known associations and reported several novel causal associations providing important insights about the cause of these diseases, which can help accelerate new prevention strategies.</p>
13 Keywords
- Atherosclerosis
- Biological Specimen Banks
- Biomarkers
- Blood Glucose
- Female
- Humans
- Lipids
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Multivariate Analysis
- Risk Factors
- United Kingdom
4 Authors
- Daniela Zanetti
- Stefan Gustafsson
- Themistocles L. Assimes
- Erik Ingelsson
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