Novel Loci for Metabolic Networks and Multi-Tissue Expression Studies Reveal Genes for Atherosclerosis

DSpace/Manakin Repository

Novel Loci for Metabolic Networks and Multi-Tissue Expression Studies Reveal Genes for Atherosclerosis

Citable link to this page

 

 
Title: Novel Loci for Metabolic Networks and Multi-Tissue Expression Studies Reveal Genes for Atherosclerosis
Author: Inouye, Michael; Ripatti, Samuli; Kettunen, Johannes; Lyytikäinen, Leo-Pekka; Oksala, Niku; Laurila, Pirkka-Pekka; Kangas, Antti J.; Soininen, Pasi; Savolainen, Markku J.; Viikari, Jorma; Kähönen, Mika; Perola, Markus; Salomaa, Veikko; Raitakari, Olli; Lehtimäki, Terho; Taskinen, Marja-Riitta; Järvelin, Marjo-Riitta; Ala-Korpela, Mika; Palotie, Aarno; de Bakker, Paul I Wen

Note: Order does not necessarily reflect citation order of authors.

Citation: Inouye, Michael, Samuli Ripatti, Johannes Kettunen, Leo-Pekka Lyytikäinen, Niku Oksala, Pirkka-Pekka Laurila, Antti J. Kangas, et al. 2012. Novel loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. PLoS Genetics 8(8): e1002907.
Full Text & Related Files:
Abstract: Association testing of multiple correlated phenotypes offers better power than univariate analysis of single traits. We analyzed 6,600 individuals from two population-based cohorts with both genome-wide SNP data and serum metabolomic profiles. From the observed correlation structure of 130 metabolites measured by nuclear magnetic resonance, we identified 11 metabolic networks and performed a multivariate genome-wide association analysis. We identified 34 genomic loci at genome-wide significance, of which 7 are novel. In comparison to univariate tests, multivariate association analysis identified nearly twice as many significant associations in total. Multi-tissue gene expression studies identified variants in our top loci, SERPINA1 and AQP9, as eQTLs and showed that SERPINA1 and AQP9 expression in human blood was associated with metabolites from their corresponding metabolic networks. Finally, liver expression of AQP9 was associated with atherosclerotic lesion area in mice, and in human arterial tissue both SERPINA1 and AQP9 were shown to be upregulated (6.3-fold and 4.6-fold, respectively) in atherosclerotic plaques. Our study illustrates the power of multi-phenotype GWAS and highlights candidate genes for atherosclerosis.
Published Version: doi:10.1371/journal.pgen.1002907
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420921/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10482575
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters