Two loci on chromosomes 2 and X for premature coronary heart disease identified in early- and late-settlement populations of Finland

Coronary heart disease (CHD) is a complex disorder constituting a major hea lth problem in Western societies. To assess the genetic background of CHD, we performed a genomewide linkage scan in two study samples from the geneti cally isolated population of Finland. An initial study sample consisted of family material from the northeastern part of Finland, settled by a small n umber of founders similar to 300 years ago. A second study sample originate d from the southwestern region of Finland, settled similar to2,000 years ag o. Families were ascertained through probands exhibiting premature CHD, def ined as >50% stenosis bf at least two coronary arteries at a young age, as verified by coronary angiography. Both study samples and the pooled data se t provided evidence for linkage in two chromosomal regions. A region on chr omosome 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 po oled 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 conc lusion, this study identifies two loci likely to contribute to premature CH D: one on chromosome 2q21.1-22 and another on chromosome Xq23-26.