title: A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case-control study.
abstract: Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other 'traditional risk factors', also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study. Twenty-nine SNPs were genotyped in 3677 stroke cases and 2415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the combined sample, and separately for the three studies. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the combined sample (OR (95% CI) 1.086 (1.029-1.147) per SD increase in the GRS P=0.003) with similar trends in all three samples: LSR (1.050 (0.967-1.140); P=0.25), MDC (1.168 (1.060-1.288); P=0.002) and SAHLSIS (1.124 (0.997-1.267); P=0.055). Measures of risk discrimination and reclassification improved marginally using the GRS. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case-control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.
authors.affiliation: 1] Department of Clinical Sciences, Lund University, Lund University Hospital of Malmö, Malmö, Sweden [2] Department of Medicine, University Hospital of Verona, Verona, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Fava
authors.affiliation: Department of Clinical Sciences, Lund University, Lund University Hospital of Malmö, Malmö, Sweden.
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sandra
authors.initials: S
authors.lastname: Olsson
authors.affiliation: Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Lövkvist
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Jood
authors.affiliation: Department of Clinical Sciences, Lund University, Lund University Hospital of Malmö, Malmö, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.affiliation: Department of Clinical Sciences, Lund University, Lund University Hospital of Malmö, Malmö, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.affiliation: Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Norrving
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Jern
authors.affiliation: 1] Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden [2] Department of Neurology, Skåne University Hospital, Lund, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Lindgren
authors.affiliation: Department of Clinical Sciences, Lund University, Lund University Hospital of Malmö, Malmö, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000150:complications; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000235:genetics*; D013548:Sweden