Faculty Collaboration Database

Quantitative founder-effect analysis of French Canadian families identifies specific loci contributing to metabolic phenotypes of hypertension. Am J Hum Genet 2005 May;76(5):815-32

Date

04/01/2005

Pubmed ID

15800845

Pubmed Central ID

PMC1199371

DOI

10.1086/430133

Scopus ID

2-s2.0-20244390026 (requires institutional sign-in at Scopus site)   69 Citations

Abstract

The Saguenay-Lac St-Jean population of Quebec is relatively isolated and has genealogical records dating to the 17th-century French founders. In 120 extended families with at least one sib pair affected with early-onset hypertension and/or dyslipidemia, we analyzed the genetic determinants of hypertension and related cardiovascular and metabolic conditions. Variance-components linkage analysis revealed 46 loci after 100,000 permutations. The most prominent clusters of overlapping quantitative-trait loci were on chromosomes 1 and 3, a finding supported by principal-components and bivariate analyses. These genetic determinants were further tested by classifying families by use of LOD score density analysis for each measured phenotype at every 5 cM. Our study showed the founder effect over several generations and classes of living individuals. This quantitative genealogical approach supports the notion of the ancestral causality of traits uniquely present and inherited in distinct family classes. With the founder effect, traits determined within population subsets are measurably and quantitatively transmitted through generational lineage, with a precise component contributing to phenotypic variance. These methods should accelerate the uncovering of causal haplotypes in complex diseases such as hypertension and metabolic syndrome.

Author List

Hamet P, Merlo E, Seda O, Broeckel U, Tremblay J, Kaldunski M, Gaudet D, Bouchard G, Deslauriers B, Gagnon F, Antoniol G, Pausová Z, Labuda M, Jomphe M, Gossard F, Tremblay G, Kirova R, Tonellato P, Orlov SN, Pintos J, Platko J, Hudson TJ, Rioux JD, Kotchen TA, Cowley AW Jr

Authors

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Canada
Female
Founder Effect
France
Genetic Linkage
Genetic Predisposition to Disease
Genetic Variation
Humans
Hypertension
Lod Score
Male
Middle Aged
Phenotype
Quantitative Trait, Heritable