associated signal for cad on chr 9 - haploview
DESCRIPTION
Associated signal for CAD on Chr 9 - haploview. CDKN =Cyclin-dependent kinase inhibitors. red boxes=recomb hotspots. LD coefficient values for SNPs genotyped in case subjects with CAD in the WTCCC. Samani et al, NEJM 2007;357:443. Replication,replication,replication…. WTCCC : Control group. - PowerPoint PPT PresentationTRANSCRIPT
Associated signal for CAD on Chr 9 - haploview
red boxes=recomb hotspots
LD coefficient values for SNPs genotyped in case subjects with CAD in the WTCCC
Samani et al, NEJM 2007;357:443
CDKN=Cyclin-dependent kinase inhibitors
Replication,replication,replication…
WTCCC : Control group• 2000 cases for each disease and 3000 common controls
• a potential for misclassification bias as phenotyping not available for controls
• it was estimated that if 5% of controls would meet the definition of cases, the loss of power is approx. the same as reduction of sample size by 10%
• however, hypertension might have had 30% not 5% misclassification bias.....
• thus “hypercontrols” would have been more suitable than common controls
GWAS & Hypertension• failure to detect a prominent
association signal in the WTCCC cannot provide conclusive exclusion of any given geneDue to:
1.1. less than complete coverage of common variation less than complete coverage of common variation genome-wide on the Affymetrix chip;genome-wide on the Affymetrix chip;
2.2. poor coverage (by design) of rare variants;poor coverage (by design) of rare variants;
3.3. despite the sample size, relatively low power to despite the sample size, relatively low power to detect variants with modest effects = OR < 1.2detect variants with modest effects = OR < 1.2
4.4. and specifically for hypertension – common and specifically for hypertension – common controls without phenotypescontrols without phenotypes
Rare functional variants under purifying selection protect against hypertension
Gitelman’sSyndr
Bartter’sSyndr
Ji et al, Nat Genet,6 April 2008
““60% reduction in 60% reduction in the risk of the risk of hypertension at age hypertension at age 60…”60…”