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

Nature Communications
Christiaan de LeeuwDanielle Posthuma

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.

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Citations

Jul 23, 2019·Psychological Medicine·Anke R HammerschlagTinca J C Polderman
Oct 28, 2019·Nature Communications·Yongbin WeiMartijn P van den Heuvel
Jul 22, 2019·Nature Communications·Kyoko WatanabeDanielle Posthuma
Aug 10, 2019·Progress in Neuro-psychopharmacology & Biological Psychiatry·Fernando Facal, Javier Costas
May 1, 2021·Journal of Clinical Medicine·Micaela F BeckmanJean-Luc C Mougeot
May 10, 2021·Biological Psychiatry·Nicholas E CliftonJeremy Hall
Aug 24, 2021·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Reyna L GordonNicole Creanza

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Methods Mentioned

BETA
genotyping

Software Mentioned

MsigDB
GSA
MAGMA
Ensembl
FlashPCA
Windows
MAGMA GSA
Linux

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