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Circulating microRNAs: Association with lung function in asthma

ABSTRACT: Blood serum from 160 Childhood Asthma Management Program (CAMP) subjects were microRNA profiles with 13 subjects profiled twice. Each subject has diverse clinical phenotypes notably spirometry related phenotypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE74770 | GEO | 2016/06/09

SECONDARY ACCESSION(S): PRJNA301451

REPOSITORIES: GEO

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Circulating microRNAs: Association with lung function in asthma

Project description:Blood serum from 160 Childhood Asthma Management Program (CAMP) subjects were microRNA profiles with 13 subjects profiled twice. Each subject has diverse clinical phenotypes notably spirometry related phenotypes. Least squares linear regression was applied with subject phenotypes as the dependent variable, and microRNA Ct values (data matrix quantile normalized) as the independent variable to identify significant associations between subject phenotype and microRNA abundance.

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Project description:Asthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. Experiment Overall Design: Gene expression levels were evaluated in 404 children. We then evaluated the relationship between SNPs in the 17q21 region (which show association to asthma in the same children) with gene expression levels. See http://www.sph.umich.edu/csg/liang/asthma/

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Genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma

Project description:Asthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. Keywords: association study, global gene expression, asthma, ORMDL3

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