Journal
STROKE
Volume 50, Issue 6, Pages 1339-1345Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.118.023097
Keywords
diabetes mellitus; genetics; hypertension; risk factors; stroke
Categories
Funding
- Emergency Medicine Foundation Career Development Grant
- American Heart Association (AHA) Mentored Clinical and Population Research Award [14CRP18860027]
- Barnes-Jewish Hospital Foundation
- Helsinki University Central Hospital
- Finnish Medical Foundation
- Finland government
- Spanish Ministry of Science and Innovation
- Instituto de Salud Carlos III (grants Registro Base de Datos de Ictus del Hospital del Mar (BASICMAR)) from Fondos de Investigacion Sanitaria Instituto de Salud Carlos III [PI051737, PI10/02064, PI12/01238, PI15/00451]
- Fondo Europeo de Desarrollo Regional (FEDER/EDRF) Red de Investigacion Cardiovascular [RD12/0042/0020]
- Fundacio la Marato TV3
- Genestroke Consortium [76/C/2011]
- Recercaixa'13 [JJ086116]
- Miguel Servet II Program
- Generacion project [PI15/01978]
- Pretest project [PMP15/00022]
- Invictus plus Network [RD16/0019]
- Instituto de Salud Carlos III
- Fondos Feder
- Agaur
- Epigenesis project from Marato TV3 Foundation
- [NIH/NINDS-R01-NS085419]
- [NIH/NINDS-K23-NS099487-01]
Ask authors/readers for more resources
Background and Purpose The genetic relationships between stroke risk, stroke severity, and early neurological changes are complex and not completely understood. Genetic studies have identified 32 all stroke risk loci. Polygenic risk scores can be used to compare the genetic architecture of related traits. In this study, we compare the genetic architecture of stroke risk, stroke severity, and early neurological changes with that of 2 stroke risk factors: type 2 diabetes mellitus (T2DM) and hypertension. Methods We assessed the degree of overlap in the genetic architecture of stroke risk, T2DM, hypertension, and 2 acute stroke phenotypes based on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 for no stroke symptoms to 21 to 42 for a severe stroke: baseline (within 6 hours after onset) and change in NIHSS (NIHSS=NIHSS at baseline-NIHSS at 24 hours). This was done by (1) single-nucleotide polymorphism by single-nucleotide polymorphism comparison, (2) weighted polygenic risk scores with sentinel variants, and (3) whole-genome polygenic risk scores using multiple P thresholds. Results We found evidence of genetic architecture overlap between stroke risk and T2DM (P=2.53x10(-169)), hypertension (P=3.93x10(-04)), and baseline NIHSS (P=0.03). However, there was no evidence of overlap between NIHSS and stroke risk, T2DM, or hypertension. Conclusions The genetic architecture of stroke risk is correlated with that of T2DM, hypertension, and initial stroke severity (NIHSS within 6 hours of stroke onset). However, the genetic architecture of early neurological change after stroke (NIHSS) is not correlated with that of ischemic stroke risk, T2DM, or hypertension. Thus, stroke risk and early neurological change after stroke have distinct genetic architectures.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available