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A family-based test for correlation between gene expression and trait values.

ABSTRACT: Advances in microarray technology have made it attractive to combine information on clinical traits, marker genotypes, and comprehensive gene expression from family studies to dissect complex disease genetics. Without accounting for family structure, methods that test for association between a trait and gene-expression levels can be misleading. We demonstrate that the standard unstratified test based on Pearson's correlation coefficient can produce spurious results when applied to family data, and we present a stratified family expression association test (FEXAT). We illustrate the utility of the FEXAT via simulation and an application to gene-expression data from lymphoblastoid cell lines from four CEPH families. The FEXAT has a smaller estimated false-discovery rate than the standard test when within-family correlations are of interest, and it detects biologically plausible correlations between beta catenin and genes in the WNT-activation pathway in humans that the standard test does not.

SUBMITTER: Kraft P

PROVIDER: S-EPMC1180286 | biostudies-literature | 2003 May

REPOSITORIES: biostudies-literature

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A family-based test for correlation between gene expression and trait values.

Kraft Peter P Schadt Eric E Aten Jason J Horvath Steve S

American journal of human genetics 20030408 5

Advances in microarray technology have made it attractive to combine information on clinical traits, marker genotypes, and comprehensive gene expression from family studies to dissect complex disease genetics. Without accounting for family structure, methods that test for association between a trait and gene-expression levels can be misleading. We demonstrate that the standard unstratified test based on Pearson's correlation coefficient can produce spurious results when applied to family data, a ...[more]

PMID: 12687497

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Project description:BackgroundEmerging evidence shows that microRNA-130 (miRNA-130) family may be useful as prognostic biomarkers in cancer. However, there is no confirmation in an independent validation study. The aim of this study was to summarize the prognostic value of miRNA-130 family (miRNA-130a and miRNA-130b) for survival in patients with cancer.MethodsThe pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the association strength between miRNA-130 family expression and prognosis. Kaplan-Meier plotters were used to verify the miRNA-130b expression and overall survival (OS).ResultsA total of 2141 patients with OS and 1159 patients with disease-free survival (DFS)/progression-free survival (PFS) were analyzed in evidence synthesis. For the miRNA-130a, the overall pooled effect size (HR) was HR 1.58 (95% CI: 1.21-2.06, P?<?0.001). Tissue and serum expression of miRNA-130a was significantly associated with the OS (HR?=?1.54, 95% CI: 1.11-2.14, P?=?0.009; HR?=?1.65, 95% CI: 1.14-2.38, P?=?0.008), and in gastric cancer (HR?=?1.81, 95% CI: 1.34-2.45, P?<?0.001). For the miRNA-13b, a statistical correlation was observed between high miRNA-130b expression and poor OS in patients with cancer (HR?=?1.95, 95% CI: 1.47-2.59, P?<?0.001), especially in tissue sample (HR?=?2.01, 95% CI: 1.39-2.91, P?<?0.001), Asian (HR?=?2.55, 95% Cl: 1.77-3.69, P?<?0.001) and hepatocellular carcinoma (HR?=?1.87, 95% CI: 1.23-2.85, P?=?0.004). The expression of miRNA-130b was significantly correlated with DFS/PFS (HR?=?1.53, 95% CI: 1.31-1.77, P?<?0.001), in tissue (HR?=?1.98, 95% CI: 1.50-2.62, P?<?0.001) and serum (HR?=?1.37, 95% CI: 1.15-1.64, P?<?0.001), especially in HCC (HR?=?1.98, 95% CI: 1.50, 2.62, P?<?0.001). In database test, a significant correlation between high miRNA-130b expression and poor OS for HCC patients was observed (HR?=?1.55, 95% CI: 1.01, 2.35, P?=?0.0045).ConclusionThe high expression of miRNA-130 family might predict poor prognosis in cancer patients. Prospectively, combining miRNA-130a and miRNA-130b may be considered as powerful prognostic predictor for clinical application.

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A family-based test for correlation between gene expression and trait values.

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A family-based test for correlation between gene expression and trait values.

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