Genetically proxied HTRA1 protease activity and circulating levels independently predict risk of ischemic stroke and coronary artery disease.

ABSTRACT: HTRA1 has emerged as a major risk gene for stroke and cerebral small vessel disease with both rare and common variants contributing to disease risk. However, the precise mechanisms mediating this risk remain largely unknown as does the full spectrum of phenotypes associated with genetic variation in HTRA1 in the general population. Using a family-history informed approach, we first show that rare variants in HTRA1 are linked to ischemic stroke in 425,338 European individuals from the UK Biobank with replication in 143,149 individuals from the Biobank Japan. Integrating data from biochemical experiments on 76 mutations occurring in the UK Biobank, we next show that rare variants causing loss of protease function in vitro associate with ischemic stroke, coronary a

SUBMITTER: Dichgans M 

PROVIDER: S-EPMC10659557 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature