Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 74, Issue 2, Pages 262-271Publisher
CELL PRESS
DOI: 10.1086/381560
Keywords
-
Categories
Funding
- NCRR NIH HHS [P41 RR003655, RR03655] Funding Source: Medline
- NHLBI NIH HHS [R01 HL66251, R01 HL065630, R01 HL65630, R01 HL066251] Funding Source: Medline
- NIGMS NIH HHS [R37 GM028356, GM28356, R01 GM028356] Funding Source: Medline
Ask authors/readers for more resources
The most frequent causes of death and disability in the Western world are atherosclerotic coronary artery disease (CAD) and acute myocardial infarction (MI). This common disease is thought to have a polygenic basis with a complex interaction with environmental factors. Here, we report results of a genomewide search for susceptibility genes for MI in a well-characterized U. S. cohort consisting of 1,613 individuals in 428 multiplex families with familial premature CAD and MI: 712 with MI, 974 with CAD, and average age of onset of 44.4+/-9.7 years. Genotyping was performed at the National Heart, Lung, and Blood Institute Mammalian Genotyping Facility through use of 408 markers that span the entire human genome every 10 cM. Linkage analysis was performed with the modified Haseman-Elston regression model through use of the SIBPAL program. Three genomewide scans were conducted: single-point, multipoint, and multipoint performed on of white pedigrees only (92% of the cohort). One novel significant susceptibility locus was detected for MI on chromosomal region 1p34-36, with a multipoint allele-sharing P value of less than or equal to10(-12) (LOD=11.68). Validation by use of a permutation test yielded a pointwise empirical P value of .00011 at this locus, which corresponds to a genomewide significance of P<.05. For the less restrictive phenotype of CAD, no genetic locus was detected, suggesting that CAD and MI may not share all susceptibility genes. The present study thus identifies a novel genetic-susceptibility locus for MI and provides a framework for the ultimate cloning of a gene for the complex disease MI.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available