Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure

Christiaan A. de Leeuw, Sven Stringer, Ilona A. Dekkers, Tom Heskes, Danielle Posthuma

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Gene-set analysis provides insight into which functional and biological properties of genes are aetiologically relevant for a particular phenotype. But genes have multiple properties, and these properties are often correlated across genes. This can cause confounding in a gene-set analysis, because one property may be statistically associated even if biologically irrelevant to the phenotype, by being correlated with gene properties that are relevant. To address this issue we present a novel conditional and interaction gene-set analysis approach, which attains considerable functional refinement of its conclusions compared to traditional gene-set analysis. We applied our approach to blood pressure phenotypes in the UK Biobank data (N = 360,243), the results of which we report here. We confirm and further refine several associations with multiple processes involved in heart and blood vessel formation but also identify novel interactions, among others with cardiovascular tissues involved in regulatory pathways of blood pressure homoeostasis.
Original languageEnglish
Article number3768
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018

Cite this

de Leeuw, Christiaan A. ; Stringer, Sven ; Dekkers, Ilona A. ; Heskes, Tom ; Posthuma, Danielle. / Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure. / de Leeuw, Christiaan A.; Stringer, Sven; Dekkers, Ilona A.; Heskes, Tom; Posthuma, Danielle.

In: Nature Communications, Vol. 9, No. 1, 3768, 2018.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure

AU - de Leeuw, Christiaan A.

AU - Stringer, Sven

AU - Dekkers, Ilona A.

AU - Heskes, Tom

AU - Posthuma, Danielle

PY - 2018

Y1 - 2018

N2 - Gene-set analysis provides insight into which functional and biological properties of genes are aetiologically relevant for a particular phenotype. But genes have multiple properties, and these properties are often correlated across genes. This can cause confounding in a gene-set analysis, because one property may be statistically associated even if biologically irrelevant to the phenotype, by being correlated with gene properties that are relevant. To address this issue we present a novel conditional and interaction gene-set analysis approach, which attains considerable functional refinement of its conclusions compared to traditional gene-set analysis. We applied our approach to blood pressure phenotypes in the UK Biobank data (N = 360,243), the results of which we report here. We confirm and further refine several associations with multiple processes involved in heart and blood vessel formation but also identify novel interactions, among others with cardiovascular tissues involved in regulatory pathways of blood pressure homoeostasis.

AB - Gene-set analysis provides insight into which functional and biological properties of genes are aetiologically relevant for a particular phenotype. But genes have multiple properties, and these properties are often correlated across genes. This can cause confounding in a gene-set analysis, because one property may be statistically associated even if biologically irrelevant to the phenotype, by being correlated with gene properties that are relevant. To address this issue we present a novel conditional and interaction gene-set analysis approach, which attains considerable functional refinement of its conclusions compared to traditional gene-set analysis. We applied our approach to blood pressure phenotypes in the UK Biobank data (N = 360,243), the results of which we report here. We confirm and further refine several associations with multiple processes involved in heart and blood vessel formation but also identify novel interactions, among others with cardiovascular tissues involved in regulatory pathways of blood pressure homoeostasis.

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