Pathway analysis following association study

Julius S. Ngwa, Alisa K. Manning, Jonna L. Grimsby, Chen Lu, Wei V. Zhuang, Anita L. Destefano

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Genome-wide association studies often emphasize single-nucleotide polymorphisms with the smallest p-values with less attention given to single-nucleotide polymorphisms not ranked near the top. We suggest that gene pathways contain valuable information that can enable identification of additional associations. We used gene set information to identify disease-related pathways using three methods: gene set enrichment analysis (GSEA), empirical enrichment p-values, and Ingenuity pathway analysis (IPA). Association tests were performed for common single-nucleotide polymorphisms and aggregated rare variants with traits Q1 and Q4. These pathway methods were evaluated by type I error, power, and the ranking of the VEGF pathway, the gene set used in the simulation model. GSEA and IPA had high power for detecting the VEGF pathway for trait Q1 (91.2% and 93%, respectively). These two methods were conservative with deflated type I errors (0.0083 and 0.0072, respectively). The VEGF pathway ranked 1 or 2 in 123 of 200 replicates using IPA and ranked among the top 5 in 114 of 200 replicates for GSEA. The empirical enrichment method had lower power and higher type I error. Thus pathway analysis approaches may be useful in identifying biological pathways that influence disease outcomes.

Original languageEnglish
Article numberS18
JournalBMC Proceedings
Volume5
Issue numberSUPPL. 9
DOIs
StatePublished - 2011
Externally publishedYes

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Genes
Vascular Endothelial Growth Factor A
Single Nucleotide Polymorphism
Polymorphism
Nucleotides
Genome-Wide Association Study

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ngwa, J. S., Manning, A. K., Grimsby, J. L., Lu, C., Zhuang, W. V., & Destefano, A. L. (2011). Pathway analysis following association study. BMC Proceedings, 5(SUPPL. 9), [S18]. https://doi.org/10.1186/1753-6561-5-S9-S18

Pathway analysis following association study. / Ngwa, Julius S.; Manning, Alisa K.; Grimsby, Jonna L.; Lu, Chen; Zhuang, Wei V.; Destefano, Anita L.

In: BMC Proceedings, Vol. 5, No. SUPPL. 9, S18, 2011.

Research output: Contribution to journalArticle

Ngwa, JS, Manning, AK, Grimsby, JL, Lu, C, Zhuang, WV & Destefano, AL 2011, 'Pathway analysis following association study', BMC Proceedings, vol. 5, no. SUPPL. 9, S18. https://doi.org/10.1186/1753-6561-5-S9-S18
Ngwa JS, Manning AK, Grimsby JL, Lu C, Zhuang WV, Destefano AL. Pathway analysis following association study. BMC Proceedings. 2011;5(SUPPL. 9). S18. https://doi.org/10.1186/1753-6561-5-S9-S18
Ngwa, Julius S. ; Manning, Alisa K. ; Grimsby, Jonna L. ; Lu, Chen ; Zhuang, Wei V. ; Destefano, Anita L. / Pathway analysis following association study. In: BMC Proceedings. 2011 ; Vol. 5, No. SUPPL. 9.
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