【bio-news】全基因组关联研究发现新的冠心病易感区域
发布于 2007-07-19 · 浏览 767 · IP 北京北京
这个帖子发布于 17 年零 324 天前，其中的信息可能已发生改变或有所发展。
http://cardiology.jwatch.org/cgi/content/full/2007/718/5?q=etoc
Homing in on Genetic Risk Factors for Coronary Artery Disease
State-of-the-art technology has enabled researchers to identify several chromosomal associations that warrant investigation.
The emergence of high-density genotyping arrays that can assess the entire genome is rapidly changing the investigation of genetic associations with disease. In two case-control studies, the Wellcome Trust Case Control Consortium (WTCCC) and the German MI Family Study, investigators used the GeneChip Human Mapping 500K Array Set, which can simultaneously type about 500,000 genetic variants, to test for genetic associations with coronary artery disease and MI.
In the WTCCC study, cases consisted of 1988 subjects with a strong family history of MI, plus MI or coronary revascularization before age 66. The German MI Family Study enrolled 875 case subjects with an MI before age 60 and at least two first-degree relatives with premature MI. The case subjects were compared with a total of 4648 controls.
The WTCCC analysis revealed 396 single-nucleotide polymorphisms significantly associated with CAD, including 30 that were clustered in nine chromosomal regions. Of these nine loci, three (9p21.3, 6q25.1, and 2q36.3) were also associated with CAD in the German study. The locus with the strongest signal in both studies, 9p21.3, contains relatively common haplotypes that were associated with a modestly increased odds ratio for CAD. The associations of 9p21.3 and 6q25.1 with CAD were not attenuated by adjustment for traditional risk factors.
Comment: This study maps the journey of discovery occurring in genetic-association research, as investigators wade through remarkable amounts of data generated by new technologies. One challenge is to seek true signals with biologic significance while avoiding false-positive findings; another is to understand the underlying mechanisms of effect. Because the loci identified in the present studies were not previously suspected to be associated with CAD, much work remains to be done to confirm the significance of the findings.
— Harlan M. Krumholz, MD, SM
Published in Journal Watch Cardiology July 18, 2007
Citation(s):
Samani NJ et al. for the WTCCC and the Cardiogenics Consortium. Genomewide association analysis of coronary artery disease. N Engl J Med 2007 Aug 2; [e-pub ahead of print]. ( http://dx.doi.org/10.1056/NEJMoa072366)
Rosenzweig A. Scanning the genome for coronary risk. N Engl J Med 2007 Aug 2; [e-pub ahead of print]. ( http://dx.doi.org/10.1056/NEJMe078121)
Drazen JM and Phimister EG. Publishing genomewide association studies. N Engl J Med 2007 Aug 2; [e-pub ahead of print]. ( http://dx.doi.org/10.1056/NEJMe078130)
Hunter DJ and Kraft P. Drinking from the fire hose — Statistical issues in genomewide association studies. N Engl J Med 2007 Aug 2; [e-pub ahead of print]. ( http://dx.doi.org/10.1056/NEJMp078120)
Homing in on Genetic Risk Factors for Coronary Artery Disease
State-of-the-art technology has enabled researchers to identify several chromosomal associations that warrant investigation.
The emergence of high-density genotyping arrays that can assess the entire genome is rapidly changing the investigation of genetic associations with disease. In two case-control studies, the Wellcome Trust Case Control Consortium (WTCCC) and the German MI Family Study, investigators used the GeneChip Human Mapping 500K Array Set, which can simultaneously type about 500,000 genetic variants, to test for genetic associations with coronary artery disease and MI.
In the WTCCC study, cases consisted of 1988 subjects with a strong family history of MI, plus MI or coronary revascularization before age 66. The German MI Family Study enrolled 875 case subjects with an MI before age 60 and at least two first-degree relatives with premature MI. The case subjects were compared with a total of 4648 controls.
The WTCCC analysis revealed 396 single-nucleotide polymorphisms significantly associated with CAD, including 30 that were clustered in nine chromosomal regions. Of these nine loci, three (9p21.3, 6q25.1, and 2q36.3) were also associated with CAD in the German study. The locus with the strongest signal in both studies, 9p21.3, contains relatively common haplotypes that were associated with a modestly increased odds ratio for CAD. The associations of 9p21.3 and 6q25.1 with CAD were not attenuated by adjustment for traditional risk factors.
Comment: This study maps the journey of discovery occurring in genetic-association research, as investigators wade through remarkable amounts of data generated by new technologies. One challenge is to seek true signals with biologic significance while avoiding false-positive findings; another is to understand the underlying mechanisms of effect. Because the loci identified in the present studies were not previously suspected to be associated with CAD, much work remains to be done to confirm the significance of the findings.
— Harlan M. Krumholz, MD, SM
Published in Journal Watch Cardiology July 18, 2007
Citation(s):
Samani NJ et al. for the WTCCC and the Cardiogenics Consortium. Genomewide association analysis of coronary artery disease. N Engl J Med 2007 Aug 2; [e-pub ahead of print]. ( http://dx.doi.org/10.1056/NEJMoa072366)
Rosenzweig A. Scanning the genome for coronary risk. N Engl J Med 2007 Aug 2; [e-pub ahead of print]. ( http://dx.doi.org/10.1056/NEJMe078121)
Drazen JM and Phimister EG. Publishing genomewide association studies. N Engl J Med 2007 Aug 2; [e-pub ahead of print]. ( http://dx.doi.org/10.1056/NEJMe078130)
Hunter DJ and Kraft P. Drinking from the fire hose — Statistical issues in genomewide association studies. N Engl J Med 2007 Aug 2; [e-pub ahead of print]. ( http://dx.doi.org/10.1056/NEJMp078120)
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