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- Title
Inbreeding and the Genetic Complexity of Human Hypertension.
- Authors
Rudan, Igor; Smolej-Narancic, Nina; Campbell, Harry; Carothers, Andrew; Wright, Alan; Janicijevic, Branka; Rudan, Pavao
- Abstract
Considerable uncertainty exists regarding the genetic architecture underlying common late-onset human diseases. In particular, the contribution of deleterious recessive alleles has been predicted to be greater for late-onset than for early-onset traits. We have investigated the contribution of recessive alleles to human hypertension by examining the effects of inbreeding on blood pressure (BP) as a quantitative trait in 2760 adult individuals frown 25 villages within Croatian island isolates. We found a strong linear relationship 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 ∼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 lochs 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. We infer that 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 I billion people globally show rates of consanguineous marriages >20%.
- Subjects
HYPERTENSION genetics; INBREEDING; BLOOD pressure
- Publication
Genetics, 2003, Vol 163, Issue 3, p1011
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1093/genetics/163.3.1011