Instrumental variable and colocalization analyses identify endotrophin and HTRA1 as potential therapeutic targets for coronary artery disease.

Coronary artery disease (CAD) remains a leading cause of disease burden globally, and there is a persistent need for new therapeutic targets. Instrumental variable (IV) and genetic colocalization analyses can help identify novel therapeutic targets for human disease by nominating causal genes in genome-wide association study (GWAS) loci. We conducted cis-IV analyses for 20,125 genes and 1,746 plasma proteins with CAD using molecular trait quantitative trait loci variant (QTLs) data from three different studies. 19 proteins and 119 genes were significantly associated with CAD risk by IV analyses and demonstrated evidence of genetic colocalization. Notably, our analyses validated well-established targets such as PCSK9 and ANGPTL4 while also identifying HTRA1 and endotrophin (a cleavage product of COL6A3) as proteins whose levels are causally associated with CAD risk. Further experimental studies are needed to confirm the causal role of the genes and proteins identified through our multiomic cis-IV analyses on human disease.

The impact of menthol flavoring in combusted tobacco on alternative product purchasing: A pilot study using the Experimental Tobacco Marketplace.

INTRODUCTION: Menthol cigarette smokers may switch to other combusted products like menthol little cigars and cigarillos (LCCs) or switch to non-combusted products like menthol vapes if menthol cigarettes are banned or otherwise restricted. This pilot study used a behavioral economics task to understand (a) menthol cigarette demand across a range of increasing prices in the context of available alternative products and (b) how the availability of menthol LCCs affected cigarette demand and alternative product substitution. METHODS: Menthol smokers completed the Experimental Tobacco Marketplace task during two sessions. Cigarettes, LCCs, smokeless tobacco, vapes, and medicinal nicotine were available from an online store. The price of menthol cigarettes increased across trials while the prices of the alternative products remained constant. Menthol LCCs were available in one session and excluded in the other. Cross-price elasticity beta estimates identified significant product substitutes. RESULTS: When menthol LCCs were available, increasing the price of menthol cigarettes led to substitution with non-menthol cigarettes (ß = 0.65, 95%CI = 0.34, 0.96), menthol little cigars (ß = 0.39, 95%CI = 0.08, 0.70), and menthol vapes (ß = 0.26, 95%CI = 0.16, 0.35). When menthol LCCs were not available, increasing the price of menthol cigarettes led to substitution with non-menthol cigarettes (ß = 0.59, 95% CI = 0.08, 1.11), non-menthol cigarillos (ß = 0.62, 95%CI = 0.19, 1.04), and menthol vapes (ß = 0.13, 95%CI = 0.08, 0.18). CONCLUSIONS: As the price of menthol cigarettes increased, demand for menthol cigarettes decreased and demand for combusted and non-combusted products increased, indicating significant substitution for menthol cigarettes. Policies targeting menthol combusted tobacco could result in some menthol smokers switching to non-combusted products like vaping devices.