Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease

Speranza Rubattu, Massimo Volpe, Reinhold Kreutz, Ursula Ganten, Detlev Ganten, Klaus Lindpaintner

Research output: Contribution to journalArticlepeer-review

Abstract

Stroke is a complex disorder with a poorly understood multifactorial and polygenic aetiology. We used the stroke-prone spontaneously hypertensive rat (SHRSP) as a model organism, mated it with the stroke-resistant spontaneously hypertensive rat (SHR) and performed a genome-wide screen in the resultant F2 cohort where latency until stroke, but not hypertension (a major confounder) segregated. We identified three major quantitative trait loci, STR1-3, with lod scores of 7.4, 4.7 and 3.0, respectively, that account for 28% of the overall phenotypic variance. STR2 colocalizes with the genes encoding atrial and brain natriuretic factor, peptides with important vasoactive properties. Our results demonstrate the existence of primary, blood pressure-independent genetic factors predisposing to a complex form of stroke.

Original languageEnglish
Pages (from-to)429-434
Number of pages6
JournalNature Genetics
Volume13
Issue number4
DOIs
Publication statusPublished - Aug 1996

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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