engleski

Effects of Inbreeding on Essential Hypertension

Considerable uncertainty exists regarding the genetic architecture underlying human quantitative traits. The contribution of recessive alleles to human hypertension has been investigated by examining the effects of inbreeding on blood pressure (BP) as a quantitative trait in 2760 adult individuals from 25 villages within a Croatian island isolate. A strong linear relationship was found between the inbreeding coefficient (F) and both systolic and diastolic BP, indicating that recessive or partially recessive quantitative trait locus (QTL) alleles account for 10-15% of the total variation in BP in this population. An increase in F of 0.01 corresponded to an increase of approximately 3 mm Hg in systolic and 2 mm Hg in diastolic BP. Regression of F on BP indicated that at least several hundred (300-600) recessive QTL contribute to BP variability. A model of the distribution of locus effects suggests that the 8-16 QTL of largest effect together account for a maximum of 25% of the dominance variation, while the remaining 75% of the variation is mediated by QTL of very small effect, unlikely to be detectable using current technologies and sample sizes. Recent inbreeding accounts for 36% of all hypertension in this population. The global impact of inbreeding on hypertension may be substantial since, although inbreeding is declining in western societies, an estimated 1 billion people globally show rates of consanguineous marriages greater than 20%. In addition, the impact of inbreeding my be greater for late-onset than for early-onset traits.

hypertension; inbreeding; isolates; Croatia

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