Large genomic study on stroke informs drug discovery and risk prediction across ancestries
Stroke is the second leading cause of death worldwide, responsible for approximately 12% of total deaths, and a major contributor to years of life lost or lived with disability.
A large international collaborative study gathering >200,000 stroke patients and >2 million control individuals from five different ancestries identifies association signals for stroke and its subtypes at 89 (61 new) independent genetic loci.
The incidence and severity of stroke is particularly high in low- and middle-income countries where 70% of total stroke deaths occur. This makes it extremely important to adopt a global perspective in research efforts aimed at improving the prevention and treatment of stroke.
The results of the largest genomic study on stroke thus far were published online in the journal Nature. The study was based on DNA samples of more than 2.5 million participants of whom 200,000 had a stroke. Participants were of European, East-Asian, African, South-Asian, and Latin-American ancestry (a third of stroke patients were non-European). They were derived from numerous hospital-based and population-based cohorts and biobanks, as well as five clinical trials.
By combining their results with existing data on gene expression in different tissues or brain cell types and protein levels in the blood, cerebrospinal fluid and brain, the researchers obtained preliminary insights into the specific genes involved and the biological mechanisms through which they may contribute to the occurrence of stroke. These findings will help translate basic research to the clinic and provide guidance to prioritize future experimental research efforts aimed at exploring possible novel drug targets for stroke.
The study was conducted by members of the GIGASTROKE consortium, involving several international consortia and networks, and investigators from over 20 countries, including Dr. Bruce Psaty, professor of medicine (General Internal Medicine) and epidemiology from the University of Washington.