title: Two loci on chromosomes 2 and X for premature coronary heart disease identified in early- and late-settlement populations of Finland.
abstract: Coronary heart disease (CHD) is a complex disorder constituting a major health problem in Western societies. To assess the genetic background of CHD, we performed a genomewide linkage scan in two study samples from the genetically isolated population of Finland. An initial study sample consisted of family material from the northeastern part of Finland, settled by a small number of founders approximately 300 years ago. A second study sample originated from the southwestern region of Finland, settled approximately 2,000 years ago. Families were ascertained through probands exhibiting premature CHD, defined as >50% stenosis of at least two coronary arteries at a young age, as verified by coronary angiography. Both study samples and the pooled data set provided evidence for linkage in two chromosomal regions. A region on chromosome 2q21.1-22 yielded two-point LOD scores of 3.2, 1.9, and 3.7, in the affected sib-pair (ASP) analyses of the northeastern, southwestern, and pooled study samples. The corresponding multipoint maximum-likelihood scores (MLSs) for these three study samples were 2.4, 1.3, and 3.0. In addition, a region on chromosome Xq23-26 resulted in two-point LOD scores of 1.9, 3.5, and 2.9 and in multipoint MLSs of 3.4, 3.1, and 2.5, respectively. In conclusion, this study identifies two loci likely to contribute to premature CHD: one on chromosome 2q21.1-22 and another on chromosome Xq23-26.
authors.affiliation: Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Pajukanta
authors.forename: M
authors.initials: M
authors.lastname: Cargill
authors.forename: L
authors.initials: L
authors.lastname: Viitanen
authors.forename: I
authors.initials: I
authors.lastname: Nuotio
authors.forename: A
authors.initials: A
authors.lastname: Kareinen
authors.forename: M
authors.initials: M
authors.lastname: Perola
authors.forename: J D
authors.initials: JD
authors.lastname: Terwilliger
authors.forename: E
authors.initials: E
authors.lastname: Kempas
authors.forename: M
authors.initials: M
authors.lastname: Daly
authors.forename: H
authors.initials: H
authors.lastname: Lilja
authors.forename: J D
authors.initials: JD
authors.lastname: Rioux
authors.forename: T
authors.initials: T
authors.lastname: Brettin
authors.forename: J S
authors.initials: JS
authors.lastname: Viikari
authors.forename: T
authors.initials: T
authors.lastname: Rönnemaa
authors.forename: M
authors.initials: M
authors.lastname: Laakso
authors.forename: E S
authors.initials: ES
authors.lastname: Lander
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D017668:Age of Onset; D000368:Aged; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003327:Coronary Disease / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D005387:Finland / Q000453:epidemiology; D018703:Founder Effect; D018740:Genetic Heterogeneity; D005819:Genetic Markers; D006801:Humans; D016013:Likelihood Functions; D008126:Lod Score; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009679:Nuclear Family; D012984:Software; D014960:X Chromosome / Q000235:genetics*
chemical_list: D005819:Genetic Markers