rs1333049

Two-marker association testing on WTCCC data identified SNP pairs associated with coronary artery disease (CAD) and hypertension (HTN). For CAD, three genes showed genome-wide significant associations: HFE2, STK32B, and DIP2C, plus a known region on 9p21 (CDKN2A/CDKN2B); HSP90B1 was found near a significant locus on chromosome 12. For HTN, five genes showed associations: GPR39, XRCC4, MYO6, ZFAT (with the lowest p-value in the study), and MACROD2, plus four non-protein-coding regions. Novel two-marker statistical methods revealed additional disease variants not detected by single-marker analysis alone.

Case-control study of 40 European Moyamoya disease patients versus 68 controls found a significant association between rs599839 (A/G, OR=2.17, 95% CI=1.17-4.05, p=0.01) in the PSRC1 gene and Moyamoya disease, along with three additional SNPs showing borderline significance in ELN and CXCL12 genes. The findings suggest shared genetic pathways between Moyamoya disease and atherosclerotic disease.

This association study tested whether GATA2 variants associate with sporadic coronary artery disease (CAD) in the Ottawa Heart Genomics Study and Cleveland Clinic populations, finding no significant association for rs2713604 or rs1573949. In 3,574 CAD cases and 2,700 controls, neither SNP showed association with angiographic CAD (p = 0.068 and p = 0.925, respectively), contradicting a prior family-based report.

This is a summary of Group 14 analyses from the Genetic Analysis Workshop 16 (GAW16) demonstrating the use of longitudinal data from the Framingham Heart Study in genome-wide association studies. Multiple analytical approaches were compared for identifying genetic associations with metabolic and cardiovascular traits including BMI, type 2 diabetes, blood pressure, lipid levels, and coronary heart disease, using various statistical methods such as linear mixed models, growth mixture modeling, and generalized estimating equations.

This replication study tested 22 candidate SNPs for association with late-onset Alzheimer's disease in 1,009 cases and 1,010 controls of Caucasian descent. While the primary analysis found no significant associations with AD risk, the study identified notable associations with age-at-onset (rs2074877 in MYH13, p=0.00196) and disease duration (rs41271951 in CTSS and rs41310885 in FAM63A, p=0.006 and p=0.0014, respectively).

This study identified seven SNPs on chromosome 9p21.3 associated with atherosclerotic stroke risk in 4,376 cases and 4,305 controls from Europe and North America. The lead SNP rs1537378 had a pooled odds ratio of 1.21 (95% CI=1.07-1.37, p=0.002) with a population attributable risk of 20.1% for atherosclerotic stroke. The associated variants are located in a region spanning over 100 kb that overlaps genes encoding ANRIL (antisense noncoding RNA), MTAP, CDKN2A, and CDKN2B, implicating this locus in vascular disease pathogenesis.

Prospective cohort study of 33,282 individuals from the MORGAM Project investigating SNPs from recent GWAS in relation to incident coronary heart disease (CHD), stroke, and total mortality. SNP rs1333049 (9p21.3) was associated with both CHD (HR=1.20, 95% CI 1.08-1.34) and stroke, rs11670734 (19q12) with total mortality and stroke, and several SNPs associated with lipid levels and blood pressure.

This comprehensive review article traces the evolution of pharmacogenetics from single-gene analysis to whole-genome approaches. It discusses validated pharmacogenetic biomarkers with clinical impact including CYP2D6, CYP2C9, CYP2C19, TPMT, DPD, VKORC1, UGT1A1, and ADRB1/ADRB2, providing examples of how genetic variants affect drug metabolism and response. The paper emphasizes the importance of integrating pharmacogenetic information into clinical practice and drug development.

This genome-wide association study investigated whether seven CAD-associated loci affect coronary artery disease risk through traditional cardiovascular risk factors. The study found that rs599839, located near PSRC1 and CELSR2 on chromosome 1p13.3, showed a strong association with serum cholesterol levels, with the risk allele A associated with 0.17 mmol/l higher total cholesterol per allele copy (P = 3.84 × 10⁻⁶) and 0.19 mmol/l higher LDL cholesterol (P = 8.56 × 10⁻⁵). This association was replicated in independent cohorts and the findings support further investigation of these genes in cholesterol metabolism and coronary risk.