Affiliation:
1. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, CA (D.Z., T.L.A., E.I.).
2. Stanford Cardiovascular Institute (D.Z., T.L.A., E.I.), Stanford University, CA.
3. Stanford Diabetes Research Center (D.Z., E.I.), Stanford University, CA.
4. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Sweden (S.G.).
Abstract
Background:
Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood.
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.
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.
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
17 articles.
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