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Novel Loci for Metabolic Networks and Multi-Tissue Expression Studies Reveal Genes for Atherosclerosis
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نویسنده
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inouye m. ,ripatti s. ,kettunen j. ,lyytikäinen l.-p. ,oksala n. ,laurila p.-p. ,kangas a.j. ,soininen p. ,savolainen m.j. ,viikari j. ,kähönen m. ,perola m. ,salomaa v. ,raitakari o. ,lehtimäki t. ,taskinen m.-r. ,järvelin m.-r. ,ala-korpela m. ,palotie a. ,de bakker p.i.w.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 8
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چکیده
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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. © 2012 inouye et al.
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آدرس
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medical systems biology,departments of pathology and of microbiology and immunology,the university of melbourne,parkville,vic,australia,immunology division,walter and eliza hall institute of medical research,parkville,vic, Australia, institute of molecular medicine (fimm),university of helsinki,helsinki,finland,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,department of human genetics,wellcome trust sanger institute,wellcome trust genome campus,hinxton, United Kingdom, institute of molecular medicine (fimm),university of helsinki,helsinki,finland,department of chronic disease prevention,national institute for health and welfare,helsinki, Finland, department of clinical chemistry,fimlab laboratories,tampere university hospital and university of tampere school of medicine,tampere, Finland, department of clinical chemistry,fimlab laboratories,tampere university hospital and university of tampere school of medicine,tampere,finland,division of vascular surgery,department of surgery,tampere university hospital,tampere, Finland, institute of molecular medicine (fimm),university of helsinki,helsinki,finland,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,department of medical genetics,university of helsinki and helsinki university hospital,helsinki, Finland, computational medicine,institute of clinical medicine,faculty of medicine,university of oulu,oulu, Finland, computational medicine,institute of clinical medicine,faculty of medicine,university of oulu,oulu,finland,nmr metabolomics laboratory,school of pharmacy,university of eastern finland,kuopio, Finland, computational medicine,institute of clinical medicine,faculty of medicine,university of oulu,oulu,finland,biocenter oulu,university of oulu,oulu,finland,department of internal medicine,clinical research center,university of oulu,oulu, Finland, department of medicine,university of turku and turku university hospital,turku, Finland, department of clinical physiology,university of tampere and tampere university hospital,tampere, Finland, department of chronic disease prevention,national institute for health and welfare,helsinki, Finland, department of chronic disease prevention,national institute for health and welfare,helsinki, Finland, research centre of applied and preventive cardiovascular medicine and dept. of clinical physiology,university of turku and turku university hospital,turku, Finland, department of clinical chemistry,fimlab laboratories,tampere university hospital and university of tampere school of medicine,tampere, Finland, department of medicine,university of helsinki,helsinki, Finland, biocenter oulu,university of oulu,oulu,finland,department of epidemiology and biostatistics,school of public health,imperial college london,london,united kingdom,department of public health science and general practice,university of oulu,oulu, Finland, computational medicine,institute of clinical medicine,faculty of medicine,university of oulu,oulu,finland,nmr metabolomics laboratory,school of pharmacy,university of eastern finland,kuopio,finland,department of internal medicine,clinical research center,university of oulu,oulu,finland,department of epidemiology and biostatistics,school of public health,imperial college london,london, United Kingdom, institute of molecular medicine (fimm),university of helsinki,helsinki,finland,department of human genetics,wellcome trust sanger institute,wellcome trust genome campus,hinxton,united kingdom,department of medical genetics,university of helsinki and helsinki university hospital,helsinki,finland,program in medical and population genetics,broad institute of harvard and mit,cambridge,ma, United States, program in medical and population genetics,broad institute of harvard and mit,cambridge,ma,united states,division of genetics,department of medicine,brigham and women's hospital,harvard medical school,boston,ma,united states,department of medical genetics,university medical center utrecht,utrecht,netherlands,department of epidemiology,university medical center utrecht,utrecht, Netherlands
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Authors
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