title: Genome-wide linkage scan of common stroke in families from northern Sweden.
abstract: OBJECTIVE
  Taking advantage of low genetic variations in northern Sweden, we performed a genome-wide linkage scan to investigate the susceptibility loci for common forms of stroke.
  
  
  METHODS
  Fifty-six families, containing multiple cases of stroke and whose data had been previously used to replicate linkage to the phosphodiesterase 4D locus on chromosome 5q, were genotyped in a genome-wide scan. Fine mapping was performed, and subsequently 53 additional families from the same region were genotyped over the candidate regions.
  
  
  RESULTS
  Linkage calculations were performed by using 3 different disease models, from a very broad (all stroke cases defined by World Health Organization MONICA criteria) to a narrower (ischemic stroke only) stroke phenotype. With all models, nonparametric multipoint linkage analysis yielded allele-sharing log of the odds (LOD) scores >1.2 at 9 locations: 1p34, 5q13, 7q35, 9q22, 9q34, 13q32, 14q32, 18p11, and 20q13. The highest allele-sharing LOD scores were obtained on chromosomes 5q (previously reported), 1p (LOD=2.09), and 18p (LOD=2.14). Fine mapping resulted in increased allele-sharing LOD scores for chromosome 5q (previously reported) and 9q22 (LOD=1.56), but all others decreased. Combining these initial results with a subsequent analysis of 53 additional families, we obtained the highest allele-sharing LOD scores on chromosomes 5q, 13q, and 18p, although none reached the initial genome-wide allele-sharing LOD scores.
  
  
  CONCLUSIONS
  Genetic analysis of stroke in families from northern Sweden did not identify any new major stroke loci. This indicates that multiple minor susceptibility loci in addition to the previously known locus on chromosome 5 could contribute to the disease.
authors.affiliation: Department of Medical Biosciences, Division of Medical and Clinical Genetics, Umeå University, 901 85 Umeå, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Nilsson-Ardnor
authors.forename: Tomas
authors.initials: T
authors.lastname: Janunger
authors.forename: Per-Gunnar
authors.initials: PG
authors.lastname: Wiklund
authors.forename: Kurt
authors.initials: K
authors.lastname: Lackovic
authors.forename: Anna Karin
authors.initials: AK
authors.lastname: Nilsson
authors.forename: Petter
authors.initials: P
authors.lastname: Lindgren
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Escher
authors.forename: Birgitta
authors.initials: B
authors.lastname: Stegmayr
authors.forename: Kjell
authors.initials: K
authors.lastname: Asplund
authors.forename: Dan
authors.initials: D
authors.lastname: Holmberg
mesh_terms: D000368:Aged; D002874:Chromosome Mapping / Q000379:methods*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology