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Integrating Genome-Wide genetic variations and monocyte expression data reveals Trans-Regulated gene modules in humans
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نویسنده
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rotival m. ,zeller t. ,wild p.s. ,maouche s. ,szymczak s. ,schillert a. ,castagné r. ,deiseroth a. ,proust c. ,brocheton j. ,godefroy t. ,perret c. ,germain m. ,eleftheriadis m. ,sinning c.r. ,schnabel r.b. ,lubos e. ,lackner k.j. ,rossmann h. ,münzel t. ,rendon a. ,consortium c. ,erdmann j. ,deloukas p. ,hengstenberg c. ,diemert p. ,montalescot g. ,ouwehand w.h. ,samani n.j. ,schunkert h. ,tregouet d.-a. ,ziegler a. ,goodall a.h. ,cambien f. ,tiret l. ,blankenberg s.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 12
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چکیده
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One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. so far,few cis expression quantitative trait loci (eqtls) have been reliably related to disease susceptibility. trans-regulating mechanisms may play a more prominent role in disease susceptibility. we analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 european unrelated subjects. we applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. these patterns were then related to 675,350 snps to identify major trans-acting regulators. we detected three genomic regions significantly associated with co-regulated gene modules. association of these loci with multiple expression traits was replicated in cardiogenics,an independent study in which expression profiles of monocytes were available in 758 subjects. the locus 12q13 (lead snp rs11171739),previously identified as a type 1 diabetes locus,was associated with a pattern including two cis eqtls,rps26 and suox,and 5 trans eqtls,one of which (madcam1) is a potential candidate for mediating t1d susceptibility. the locus 12q24 (lead snp rs653178),which has demonstrated extensive disease pleiotropy,including type 1 diabetes,hypertension,and celiac disease,was associated to a pattern strongly correlating to blood pressure level. the strongest trans eqtl in this pattern was crip1,a known marker of cellular proliferation in cancer. the locus 12q15 (lead snp rs11177644) was associated with a pattern driven by two cis eqtls,lyz and yeats4,and including 34 trans eqtls,several of them tumor-related genes. this study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the mechanisms linking genome-wide association loci to disease. © 2011 rotival et al.
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آدرس
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inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz,germany,department of general and interventional cardiology,university heart center,university medical center hamburg-eppendorf,hamburg, Germany, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz, Germany, medizinische klinik ii,universität lübeck,lübeck, Germany, institut für medizinische biometrie und statistik,universität lübeck,lübeck, Germany, institut für medizinische biometrie und statistik,universität lübeck,lübeck, Germany, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz, Germany, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz, Germany, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz,germany,department of general and interventional cardiology,university heart center,university medical center hamburg-eppendorf,hamburg, Germany, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz,germany,department of general and interventional cardiology,university heart center,university medical center hamburg-eppendorf,hamburg, Germany, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz,germany,department of general and interventional cardiology,university heart center,university medical center hamburg-eppendorf,hamburg, Germany, institut für klinische chemie und laboratoriumsmedizin,universitätsmedizin der johannes-gutenberg universität mainz,mainz, Germany, institut für klinische chemie und laboratoriumsmedizin,universitätsmedizin der johannes-gutenberg universität mainz,mainz, Germany, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz, Germany, department of haematology,university of cambridge,national health service blood and transplant,cambridge,united kingdom,mrc biostatistics unit,cambridge, United Kingdom, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, medizinische klinik ii,universität lübeck,lübeck, Germany, human genetics,wellcome trust sanger institute,hinxton, United Kingdom, klinik und poliklinik für innere medizin ii,universität regensburg,regensburg, Germany, medizinische klinik ii,universität lübeck,lübeck,germany,department of general and interventional cardiology,university heart center,university medical center hamburg-eppendorf,hamburg, Germany, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, department of haematology,university of cambridge,national health service blood and transplant,cambridge,united kingdom,human genetics,wellcome trust sanger institute,hinxton, United Kingdom, department of cardiovascular sciences,university of leicester,leicester,united kingdom,leicester nihr biomedical research unit in cardiovascular disease,leicester, United Kingdom, medizinische klinik ii,universität lübeck,lübeck, Germany, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, institut für medizinische biometrie und statistik,universität lübeck,lübeck, Germany, department of cardiovascular sciences,university of leicester,leicester,united kingdom,leicester nihr biomedical research unit in cardiovascular disease,leicester, United Kingdom, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, inserm umrs 937,pierre and marie curie university (upmc,paris 6) and medical school,paris, France, ii. medizinische klinik und poliklinik,universitätsmedizin der johannes-gutenberg universität mainz,mainz,germany,department of general and interventional cardiology,university heart center,university medical center hamburg-eppendorf,hamburg, Germany
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Authors
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