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Lung eQTLs to Help Reveal the Molecular Underpinnings of Asthma
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نویسنده
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hao k. ,bossé y. ,nickle d.c. ,paré p.d. ,postma d.s. ,laviolette m. ,sandford a. ,hackett t.l. ,daley d. ,hogg j.c. ,elliott w.m. ,couture c. ,lamontagne m. ,brandsma c.-a. ,van den berge m. ,koppelman g. ,reicin a.s. ,nicholson d.w. ,malkov v. ,derry j.m. ,suver c. ,tsou j.a. ,kulkarni a. ,zhang c. ,vessey r. ,opiteck g.j. ,curtis s.p. ,timens w. ,sin d.d.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 11
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چکیده
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Genome-wide association studies (gwas) have identified loci reproducibly associated with pulmonary diseases; however,the molecular mechanism underlying these associations are largely unknown. the objectives of this study were to discover genetic variants affecting gene expression in human lung tissue,to refine susceptibility loci for asthma identified in gwas studies,and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. we performed a genome-wide search for expression quantitative trait loci (eqtl) in 1,111 human lung samples. the lung eqtl dataset was then used to inform asthma genetic studies reported in the literature. the top ranked lung eqtls were integrated with the gwas on asthma reported by the gabriel consortium to generate a bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. we detected 17,178 cis- and 593 trans- lung eqtls,which can be used to explore the functional consequences of loci associated with lung diseases and traits. some strong eqtls are also asthma susceptibility loci. for example,rs3859192 on chr17q21 is robustly associated with the mrna levels of gsdma (p = 3.55×10-151). the genetic-gene expression network identified the socs3 pathway as one of the key drivers of asthma. the eqtls and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. this data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases. © 2012 hao et al.
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آدرس
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merck research laboratories,boston,ma,united states,merck,rahway,nj,united states,genetics,rosetta inpharmatics,merck,seattle,wa, United States, department of molecular medicine,laval university,québec city,canada,institut universitaire de cardiologie et de pneumologie de québec,laval university,québec city, Canada, merck research laboratories,boston,ma,united states,merck,rahway,nj,united states,genetics,rosetta inpharmatics,merck,seattle,wa, United States, the university of british columbia james hogg research laboratory,st paul's hospital,vancouver,canada,respiratory division,department of medicine,university of british columbia,vancouver, Canada, department of pulmonology,university medical center groningen,griac research institute,university of groningen,groningen, Netherlands, institut universitaire de cardiologie et de pneumologie de québec,laval university,québec city, Canada, the university of british columbia james hogg research laboratory,st paul's hospital,vancouver,canada,respiratory division,department of medicine,university of british columbia,vancouver, Canada, the university of british columbia james hogg research laboratory,st paul's hospital,vancouver, Canada, the university of british columbia james hogg research laboratory,st paul's hospital,vancouver,canada,respiratory division,department of medicine,university of british columbia,vancouver, Canada, the university of british columbia james hogg research laboratory,st paul's hospital,vancouver,canada,department of pathology and laboratory medicine,university of british columbia,vancouver, Canada, the university of british columbia james hogg research laboratory,st paul's hospital,vancouver, Canada, institut universitaire de cardiologie et de pneumologie de québec,laval university,québec city, Canada, institut universitaire de cardiologie et de pneumologie de québec,laval university,québec city, Canada, department of pathology and medical biology,university medical center groningen,griac research institute,university of groningen,groningen, Netherlands, department of pulmonology,university medical center groningen,griac research institute,university of groningen,groningen, Netherlands, department of pediatric pulmonology,university medical center groningen,university of groningen,groningen, Netherlands, merck,rahway,nj, United States, merck,rahway,nj, United States, merck,rahway,nj, United States, sage bionetworks,seattle,wa, United States, sage bionetworks,seattle,wa, United States, merck,rahway,nj, United States, merck,rahway,nj, United States, merck,rahway,nj, United States, merck,rahway,nj, United States, merck,rahway,nj, United States, merck,rahway,nj, United States, department of pathology and medical biology,university medical center groningen,griac research institute,university of groningen,groningen, Netherlands, the university of british columbia james hogg research laboratory,st paul's hospital,vancouver,canada,respiratory division,department of medicine,university of british columbia,vancouver, Canada
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Authors
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