title: Are common disease susceptibility alleles the same in outbred and founder populations?
abstract: Founder populations have been the subjects of complex disease studies because of their decreased genetic heterogeneity, increased linkage disequilibrium and more homogeneous environmental exposures. However, it is possible that disease alleles identified in founder populations may not contribute significantly to susceptibility in outbred populations. In this study we examine the Hutterites, a founder population of European descent, for 103 polymorphisms in 66 genes that are candidates for cardiovascular or inflammatory diseases. We compare the frequencies of alleles at these loci in the Hutterites to their frequencies in outbred European-American populations and test for associations with cardiovascular disease-associated phenotypes in the Hutterites. We show that alleles at these loci are found at similar frequencies in the Hutterites and in outbred populations. In addition, we report associations between 39 alleles or haplotypes and cardiovascular disease phenotypes (P<0.05), with five loci remaining significant after adjusting for multiple comparisons. These data indicate that this founder population is informative and offers considerable advantages for genetic studies of common complex diseases.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA. dnewman@mail.rit.edu
authors.forename: Dina L
authors.initials: DL
authors.lastname: Newman
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffjan
authors.forename: Catherine
authors.initials: C
authors.lastname: Bourgain
authors.forename: Mark
authors.initials: M
authors.lastname: Abney
authors.forename: Raluca I
authors.initials: RI
authors.lastname: Nicolae
authors.forename: Elle T
authors.initials: ET
authors.lastname: Profits
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grow
authors.forename: Karen
authors.initials: K
authors.lastname: Walker
authors.forename: Lori
authors.initials: L
authors.lastname: Steiner
authors.forename: Rodney
authors.initials: R
authors.lastname: Parry
authors.forename: Rebecca
authors.initials: R
authors.lastname: Reynolds
authors.forename: Mary Sara
authors.initials: MS
authors.lastname: McPeek
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cheng
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics