Combining genetic analyses in large international biobanks with experimental studies on human cells, ISD investigators found that rare HTRA1 variants affect vascular risk via a loss of enzymatic function of the HTRA1 protease, whereas a common causal variant independently affects vascular risk by influencing the circulating HTRA1 mRNA and protein levels. They further uncovered a complex relationship with other diseases including migraine and macular dystrophy.

Dichgans M, Malik R, Beaufort N, Tanaka K, Georgakis M, He Y, Koido M, Terao C, Anderson C, Kamatani Y. Genetically proxied HTRA1 protease activity and circulating levels independently predict risk of ischemic stroke and coronary artery disease. Res Sq [Preprint]. 2023 Nov 7:rs.3.rs-3523612. doi: 10.21203/rs.3.rs-3523612/v1.