What is Mendelian randomization?

Asundexian's genetic signal was strongest for cardioembolic stroke, yet the drug failed specifically in atrial fibrillation patients at high cardioembolic risk, while showing promise in non-cardioembolic stroke, upending the logic of Mendelian randomization target selection.

“Variation was more strongly associated with cardiamolic stroke although there was a strong signal also for non-cardiamolic stroke but when asend was tested in atrial fibrillation patients against modern anticoagulants aixaban riveroxaban and so on it failed to show efficacy the study stopped early it was discontinued because actually the drug performed worse than modern anticoagulants.”

Mendelian randomization shows CRP is not a causal cardiovascular target: genetic variants in the CRP gene that raise CRP levels show no association with coronary artery disease risk.

“We find genetic variants within the gene coding CRP that influence CRP levels. those genetic variants do not show any association with the risk of coronary artery disease or other cardiovascular disease endpoints.”

Mendelian randomization shows HDL is not a causal cardiovascular target: genetic variants that raise HDL without affecting LDL do not reduce cardiovascular disease risk.

“If we find variants that raise HDL but have no influence on LDL cholesterol, they do not influence the risk of cardiovascular disease.”

Genetically low vitamin D levels causally raise all-cause mortality per Mendelian randomization, countering the view that the vitamin D-mortality link is merely observational confounding.

“People with those genes, their they have genetically low levels of vitamin D, they have a higher all-cause mortality than people that don't have those genes.”

Georgakis et al. paper published in Nature Cardiovascular Research providing new genetic evidence that IL-6 ligand variants associate with lower IL-6 expression, lower CRP, and reduced atherosclerotic risk.

“That's that's a paper published last year in nature cardiovascular research if we leverage modern genetic data sets we can actually also find genetic variants in the lus of the intellin 6 lian itself that are associated with lower expression.”