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A genomewide linkage study of 1,933 families affected by premature coronary artery disease: The British Heart Foundation (BHF) Family Heart Study.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2005 Dec; Vol. 77 (6), pp. 1011-20. Date of Electronic Publication: 2005 Oct 25. - Publication Year :
- 2005
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Abstract
- Coronary artery disease (CAD) and its most important complication, myocardial infarction (MI), are the leading cause of premature death in the Western world. CAD has a substantial genetic basis, especially when it occurs early. We investigated the genetic determinants of premature CAD by performing a genomewide linkage analysis of 4,175 affected subjects from 1,933 families recruited throughout the United Kingdom. Each family had at least two available siblings with CAD, with validated onset before age 66 years. Linkage analysis was performed using 416 microsatellite markers. We observed suggestive linkage, for both CAD and MI, to a region on chromosome 2. For CAD, a LOD score of 1.86 was observed at marker D2S2271, which, in an ordered subset analysis, increased to 2.70 in families (n=1,698) with a minimum age at diagnosis of 56 years or younger. For MI, an overlapping peak with a LOD score of 1.15 was observed at marker D2S2216, which increased to 2.1 in families (n=801) with a minimum age at diagnosis of 59 years or younger. Exclusion mapping showed that 100% of the autosomal genome could be excluded for locus-specific sibling relative risks of 1.5 and 1.6 for CAD and MI, respectively. The region identified on chromosome 2 overlaps linked regions observed in two other smaller genome scans for CAD. Together, these findings strongly suggest that there is a locus on chromosome 2 that influences coronary atherosclerosis risk. The exclusion of a common locus that increases risk of CAD to siblings by >50% has important implications for strategies for further defining the genetic basis of CAD.
- Subjects :
- Age of Onset
Chromosome Mapping
Chromosomes, Human, Pair 2
Diseases in Twins genetics
Diseases in Twins pathology
Family Health
Genetic Markers
Humans
Lod Score
Microsatellite Repeats
Myocardial Infarction complications
Myocardial Infarction genetics
Myocardial Infarction pathology
Reproducibility of Results
Risk
Siblings
Twins, Monozygotic genetics
United Kingdom epidemiology
Coronary Artery Disease genetics
Coronary Artery Disease pathology
Coronary Vessels pathology
Genetic Linkage
Genome, Human
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9297
- Volume :
- 77
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 16380912
- Full Text :
- https://doi.org/10.1086/498653