The multiplicity problem in linkage analysis of gene expression data – the power of differentiating cis- and trans-acting regulators
2007

Improving Gene Expression Analysis with Stratified False Discovery Rate Control

Sample size: 3855428 publication Evidence: moderate

Author Information

Author(s): Huang Baisong, Rangrej Jagadish, Paterson Andrew D, Sun Lei

Primary Institution: Research Institute, Hospital for Sick Children

Hypothesis

Can the stratified false-discovery rate control method improve the performance of genome-wide linkage analyses compared to traditional methods?

Conclusion

The stratified false-discovery rate method outperformed the traditional aggregated approach in identifying true positives in gene expression data.

Supporting Evidence

  • The stratified method provided 57 more true positives while controlling the FDR at the same rate as the aggregated approach.
  • Among the 9,069,390 tests, more than half had p-values equal to 1, indicating a significant association with H2 = 0.
  • The cis stratum contained a relatively higher proportion of true signals than the trans stratum.

Takeaway

This study shows that using special methods to analyze gene data can help find more true signals and reduce mistakes.

Methodology

The study performed eQTL analysis using MERLIN and compared the stratified FDR method with traditional aggregated approaches under three frameworks.

Limitations

The stratified method did not outperform the aggregated approach by as large a margin as expected due to the overwhelming number of trans regulators.

Statistical Information

P-Value

1

Statistical Significance

p<0.0001

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