Dataset Information

Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.

ABSTRACT: Myocardial infarction (MI) is a common complex disease with a genetic component. While several single nucleotide polymorphisms (SNPs) have been reported to be associated with risk of MI, they do not fully explain the observed genetic component of MI. We have been investigating the association between MI and SNPs that are located in genes and have the potential to affect gene function or expression. We have previously published studies that tested about 12,000 SNPs for association with risk of MI, early-onset MI, or coronary stenosis. In the current study we tested 17,576 SNPs that could affect gene function or expression. In order to use genotyping resources efficiently, we staged the testing of these SNPs in three case-control studies of MI. In the first study (762 cases, 857 controls) we tested 17,576 SNPs and found 1,949 SNPs that were associated with MI (P<0.05). We tested these 1,949 SNPs in a second study (579 cases and 1159 controls) and found that 24 SNPs were associated with MI (1-sided P<0.05) and had the same risk alleles in the first and second study. Finally, we tested these 24 SNPs in a third study (475 cases and 619 controls) and found that 5 SNPs in 4 genes (ENO1, FXN (2 SNPs), HLA-DPB2, and LPA) were associated with MI in the third study (1-sided P<0.05), and had the same risk alleles in all three studies. The false discovery rate for this group of 5 SNPs was 0.23. Thus, we have identified 5 SNPs that merit further examination for their potential association with MI. One of these SNPs (in LPA), has been previously shown to be associated with risk of cardiovascular disease in other studies.

SUBMITTER: Shiffman D

PROVIDER: S-EPMC2483345 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.

Shiffman Dov D Kane John P JP Louie Judy Z JZ Arellano Andre R AR Ross David A DA Catanese Joseph J JJ Malloy Mary J MJ Ellis Stephen G SG Devlin James J JJ

PloS one 20080806 8

Myocardial infarction (MI) is a common complex disease with a genetic component. While several single nucleotide polymorphisms (SNPs) have been reported to be associated with risk of MI, they do not fully explain the observed genetic component of MI. We have been investigating the association between MI and SNPs that are located in genes and have the potential to affect gene function or expression. We have previously published studies that tested about 12,000 SNPs for association with risk of MI ...[more]

PMID: 18682748

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Project description:Peripheral blood samples of patients with acute myocardial infarction were matched with those of control patients to identify possible differences in corresponding gene expression profiles. The controls were matched to cases based on gender, age, status of diabetes mellitus and smoking status. Six months cardiovascular survival status of the cases was used to identify two distinct subgroups among the cases. Linear models for microarray data (M-bM-^@M-^XlimmaM-bM-^@M-^Y) were employed to identify differential gene expression. Shrunken centroids technique helped in identifying the subsets of differentially expressed genes with predictive properties in independent samples. Predictive properties were evaluated using bootstrap sampling. Using the limma modeling with the log-fold change threshold of one (clinical significance) and StoreyM-bM-^@M-^Ys q-value approach (statistical significance), sixty transcripts were found to be both clinically and statistically differentially expressed among the cases not surviving the follow-up period relative to controls, while no such transcripts were observed among other surviving cases. The two subgroups of cases exhibited fourteen differentially expressed transcripts. Predictive modeling indicated sixteen out of sixty transcripts to best discriminate between the controls and cases who died during the follow-up period from cardiovascular causes, while for the surviving cases the already non-significant set of transcripts could not be further reduced. Eleven out of fourteen transcripts were found to best discriminate between the two groups of cases using shrunken centroids. The study identified genes, which were differentially expressed during the acute myocardial infarction, including those associated with short-term fatality of the cases. The genome-wide study used matched case-control design, with 97 samples of 90 patients in three disease groups. Matched control samples were used and several (7) technical replicates were performed.

Dataset Information

Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.

Publications

Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.

Similar Datasets

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