Genome-wide linkage scan of common stroke in families from northern Sweden.
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.
Nilsson-Ardnor
Sofie
S
Department of Medical Biosciences, Division of Medical and Clinical Genetics, Umeå University, 901 85 Umeå, Sweden.
Janunger
Tomas
T
Wiklund
Per-Gunnar
PG
Lackovic
Kurt
K
Nilsson
Anna Karin
AK
Lindgren
Petter
P
Escher
Stefan A
SA
Stegmayr
Birgitta
B
Asplund
Kjell
K
Holmberg
Dan
D
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