Dataset Information

Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies.

ABSTRACT: Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) at multiple loci that are significantly associated with coronary artery disease (CAD) risk. In this study, we sought to determine and compare the predictive capabilities of 9p21.3 alone and a panel of SNPs identified and replicated through GWAS for CAD.We used the Ottawa Heart Genomics Study (OHGS) (3323 cases, 2319 control subjects) and the Wellcome Trust Case Control Consortium (WTCCC) (1926 cases, 2938 control subjects) data sets. We compared the ability of allele counting, logistic regression, and support vector machines. Two sets of SNPs, 9p21.3 alone and a set of 12 SNPs identified by GWAS and through a model-fitting procedure, were considered. Performance was assessed by measuring area under the curve (AUC) for OHGS using 10-fold cross-validation and WTCCC as a replication set. AUC for logistic regression using OHGS increased significantly from 0.555 to 0.608 (P=3.59×10?¹?) for 9p21.3 versus the 12 SNPs, respectively. This difference remained when traditional risk factors were considered in a subgroup of OHGS (1388 cases, 2038 control subjects), with AUC increasing from 0.804 to 0.809 (P=0.037). The added predictive value over and above the traditional risk factors was not significant for 9p21.3 (AUC 0.801 versus 0.804, P=0.097) but was for the 12 SNPs (AUC 0.801 versus 0.809, P=0.0073). Performance was similar between OHGS and WTCCC. Logistic regression outperformed both support vector machines and allele counting.Using the collective of 12 SNPs confers significantly greater predictive capabilities for CAD than 9p21.3, whether traditional risks are or are not considered. More accurate models probably will evolve as additional CAD-associated SNPs are identified.

SUBMITTER: Davies RW

PROVIDER: S-EPMC3035486 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies.

Davies Robert W RW Dandona Sonny S Stewart Alexandre F R AF Chen Li L Ellis Stephan G SG Tang W H Wilson WH Hazen Stanley L SL Roberts Robert R McPherson Ruth R Wells George A GA

Circulation. Cardiovascular genetics 20100821 5

<h4>Background</h4>Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) at multiple loci that are significantly associated with coronary artery disease (CAD) risk. In this study, we sought to determine and compare the predictive capabilities of 9p21.3 alone and a panel of SNPs identified and replicated through GWAS for CAD.<h4>Methods and results</h4>We used the Ottawa Heart Genomics Study (OHGS) (3323 cases, 2319 control subjects) and the Wellcome Trust ...[more]

PMID: 20729558

Similar Datasets

Project description:Study questionAre the single nucleotide polymorphisms (SNPs) rs2075230, rs6259 and rs727428 at the sex hormone-binding globulin (SHBG) locus, which were identified by genome-wide association studies (GWASs) for testosterone levels, associated with testosterone levels in Japanese men?Summary answerThe SNP rs2075230, but not rs6259 and rs727428, is significantly associated with testosterone levels in Japanese men.What is already knownPrevious GWASs have revealed that rs2075230 is associated with serum testosterone levels in 3495 Chinese men and rs6259 and rs727428 are associated with serum testosterone levels in 3225 men of European ancestry.Study design size and durationThis is an independent validation study of 1687 Japanese men (901 in Cohort 1 and 786 in Cohort 2).Participants/materials setting and methodCohort 1 (20.7 ± 1.7 years old, mean ± SD) and Cohort 2 (31.2 ± 4.8 years) included samples obtained from university students and partners of pregnant women, respectively. The three SNPs were genotyped using either TaqMan probes or restriction fragment length polymorphism PCR. Blood samples were drawn from the cubital vein of the study participants in the morning, and total testosterone and SHBG levels were measured using a time-resolved immunofluorometric assay. Association between each SNP and testosterone levels was evaluated by meta-analysis of the two Japanese male cohorts.Main results and the role of chanceThe age of the two cohorts was significantly different (P < 0.0001). We found that rs2075230 was significantly associated with serum testosterone levels (β STD = 0.15, P = 7.2 × 10-6); however, rs6259 and rs727428 were not (β STD = 0.17, P = 0.071; β STD = 0.082, P = 0.017, respectively), after adjusting for multiple testing in a combined analysis of two Japanese male cohorts. Moreover, rs2075230, rs6259 and rs727428 were significantly associated with high SHBG levels (β STD = 0.22, P = 3.4 × 10-12; β STD = 0.23, P = 6.5 × 10-6 and β STD = 0.21, P = 3.4 × 10-10, respectively).Large scale dataNot applicable.Limitations reasons for cautionThis study had differences in the age and background parameters of participants compared to those observed in previous GWASs. In addition, the average age of participants in the two cohorts in our study also differed from one another. Therefore, the average testosterone levels, which decrease with age, between studies or the two cohorts were different.Wider implications of the findingsThe three SNPs have a considerable effect on SHBG levels and hence may indirectly affect testosterone levels.Study funding/competing interestsThis study was supported partly by the Ministry of Health and Welfare of Japan (1013201) (to T.I.), Grant-in-Aids for Scientific Research (C) (26462461) (to Y.S.) and (23510242) (to A.Ta.) from the Japan Society for the Promotion of Science, the European Union (BMH4-CT96-0314) (to T.I.) and the Takeda Science Foundation (to A.Ta.). There are no conflicts of interest to declare.

Dataset Information

Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies.

Publications

Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets