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LATE-BREAKING ABSTRACT: Genome-wide association studies identify novel loci associated with early postnatal lung function

Olga Gorlanova, Jakob Usemann, Philipp Latzin, Anne Schmidt, Sven Michel, Antoaneta Toncheva, Michael Kabesch, Urs Frey
European Respiratory Journal 2015 46: PA1222; DOI: 10.1183/13993003.congress-2015.PA1222
Olga Gorlanova
1Pediatric Pulmonology, University Children's Hospital (UKBB), Basel, Switzerland
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Jakob Usemann
1Pediatric Pulmonology, University Children's Hospital (UKBB), Basel, Switzerland
2Pediatric Respiratory Medicine, Inselspital and University of Bern, Bern, Switzerland
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Philipp Latzin
1Pediatric Pulmonology, University Children's Hospital (UKBB), Basel, Switzerland
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Anne Schmidt
1Pediatric Pulmonology, University Children's Hospital (UKBB), Basel, Switzerland
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Sven Michel
3Paediatric Pneumology and Allergy, KUNO Children's Hospital Regensburg, Regensburg, Germany
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Antoaneta Toncheva
3Paediatric Pneumology and Allergy, KUNO Children's Hospital Regensburg, Regensburg, Germany
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Michael Kabesch
3Paediatric Pneumology and Allergy, KUNO Children's Hospital Regensburg, Regensburg, Germany
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Urs Frey
1Pediatric Pulmonology, University Children's Hospital (UKBB), Basel, Switzerland
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Abstract

Introduction: Genetic determinants of neonatal lung function assessed prior to infections and environmental risk factors are still poorly understood.

Objective: We aimed to identify genetic variants influencing postnatal lung function, adjusted for pre- and perinatal risk factors.

Methods: We performed the quantitative genome-wide association study (GWAS) of several lung function parameters measured in term healthy infants aged 1 month. Minute ventilation (VE), tidal volume (VT), maximal mid expiratory flow at 50% (MEF50%), and the ratio of time to reach peak tidal expiratory flow to the total expiratory time (tPTEF/tE) were investigated within the Basel-Bern Infant Lung Development (BILD) birth cohort (n=229).

Results: We identified a significant association between VE and rs10076782 that is located in the intron region of RNF145 (126.3 ml decrease per risk allele, p-value=2.1×10-8). This locus has been reported previously to be nominally associated with abnormal lung function in adults. SNP rs10076782 also showed some evidence for an association with the MEF50% (p-value 5.03×10-6). In silico analyses revealed that rs10076782 covers a tagging bin comprising 16 SNPs (r2≥0.8). Of these, 8 are located within evolutionary conserved regions. Moreover, those variants were predicted to modulate transcription factors (TFs) binding patterns.

Conclusion: Our GWAS data indicate that RNF145 locus may be involved in lung growth and development. In silico predictions point towards differential TF binding dependent on the presence of alleles in high linkage disequilibrium with rs10076782. Further gene expression studies are needed to evaluate the functional relevance of these findings.

  • Lung function testing
  • Genetics
  • Lung growth/development
  • Copyright ©ERS 2015
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LATE-BREAKING ABSTRACT: Genome-wide association studies identify novel loci associated with early postnatal lung function
Olga Gorlanova, Jakob Usemann, Philipp Latzin, Anne Schmidt, Sven Michel, Antoaneta Toncheva, Michael Kabesch, Urs Frey
European Respiratory Journal Sep 2015, 46 (suppl 59) PA1222; DOI: 10.1183/13993003.congress-2015.PA1222

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LATE-BREAKING ABSTRACT: Genome-wide association studies identify novel loci associated with early postnatal lung function
Olga Gorlanova, Jakob Usemann, Philipp Latzin, Anne Schmidt, Sven Michel, Antoaneta Toncheva, Michael Kabesch, Urs Frey
European Respiratory Journal Sep 2015, 46 (suppl 59) PA1222; DOI: 10.1183/13993003.congress-2015.PA1222
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