Academic Editor: Jane A. Leopold
Background: Higher age-specific circulating anti-Müllerian hormone
(AMH) levels have been linked to a lower risk of cardiometabolic outcomes.
However, whether AMH has a casual role in the etiology of these diseases is
unknown. The objective of this study was therefore to explore if circulating AMH
levels have a causal effect on risk of coronary artery disease (CAD), ischemic
stroke and type 2 diabetes (T2D) in women, using a two-sample Mendelian
randomization (MR) approach. Methods: We used four single nucleotide
polymorphisms (SNPs) from the most recent AMH GWAS meta-analysis as instrumental
variables. Summary-level data for CAD (n = 149,752; 11,802 cases), ischemic
stroke (n = 17,541; 4678 cases) and T2D (n = 464,389; 30,052 cases) were
extracted from the UK Biobank, the Stroke Genetics Network, and DIAMANTE
consortia, respectively. To assess the presence of potential pleiotropy we tested
the association of the four AMH SNPs, both individually and combined in a
weighted genetic risk score, with a range of cardiovascular risk factors and
intermediate traits using UK Biobank data. Results: MR estimates, i.e.,
inverse variance-weighted odds ratios (OR