University of Oulu

Mahlman, M., Karjalainen, M., Huusko, J., Andersson, S., Kari, M., Tammela, O., Sankilampi, U., Lehtonen, L., Marttila, R., Bassler, D., Poets, C., Lacaze-Masmonteil, T., Danan, C., Delacourt, C., Palotie, A., Muglia, L., Lavoie, P., Hadchouel, A., Rämet, M., Hallman, M. (2017) Genome-wide association study of bronchopulmonary dysplasia: a potential role for variants near the CRP gene. Scientific Reports, 7 (1), doi:10.1038/s41598-017-08977-w

Genome-wide association study of bronchopulmonary dysplasia : a potential role for variants near the CRP gene

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Author: Mahlman, Mari1,2; Karjalainen, Minna K.1,2; Huusko, Johanna M.1,2,3;
Organizations: 1PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu
2Department of Children and Adolescents, Oulu University Hospital
3Perinatal Institute, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine
4Children’s Hospital, University of Helsinki, and Helsinki University Hospital
5Tampere University Hospital, Tampere University, and Center of Pediatric Child Health
6Department of Pediatrics, Kuopio University Hospital
7Turku University Hospital, and the University of Turku
8Department of Neonatology, University Hospital Zurich, and University of Zurich
9Department of Neonatology, Tuebingen University Hospital
10Department of Paediatrics, Cumming School of Medicine, University of Calgary
11Inserm, U955
12CRB, CHI-Creteil
13Department of neonatology, CHI-Creteil
14AP-HP, Hôpital Necker-Enfants Malades, Service de Pneumologie Pédiatrique
15Université Paris-Descartes
16Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital
17Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard
18The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard
19Institute for Molecular Medicine Finland, University of Helsinki
20Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital
21Department of Neurology, Massachusetts General Hospital
22BC Children’s Hospital Research Institute
23BioMediTech Institute and Faculty of Medical and Life Sciences, University of Tampere
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe201709258730
Language: English
Published: Nature Publishing Group, 2017
Publish Date: 2017-09-25
Description:

Abstract

Bronchopulmonary dysplasia (BPD), the main consequence of prematurity, has a significant heritability, but little is known about predisposing genes. The aim of this study was to identify gene loci predisposing infants to BPD. The initial genome-wide association study (GWAS) included 174 Finnish preterm infants of gestational age 24–30 weeks. Thereafter, the most promising single-nucleotide polymorphisms (SNPs) associated with BPD were genotyped in both Finnish (n = 555) and non-Finnish (n = 388) replication cohorts. Finally, plasma CRP levels from the first week of life and the risk of BPD were assessed. SNP rs11265269, flanking the CRP gene, showed the strongest signal in GWAS (odds ratio [OR] 3.2, p = 3.4 × 10⁻⁶). This association was nominally replicated in Finnish and French African populations. A number of other SNPs in the CRP region, including rs3093059, had nominal associations with BPD. During the first week of life the elevated plasma levels of CRP predicted the risk of BPD (OR 3.4, p = 2.9 × 10⁻⁴) and the SNP rs3093059 associated nominally with plasma CRP levels. Finally, SNP rs11265269 was identified as a risk factor of BPD (OR 1.8, p = 5.3 × 10⁻⁵), independently of the robust antenatal risk factors. As such, in BPD, a potential role for variants near CRP gene is proposed.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 7
Article number: 9271
DOI: 10.1038/s41598-017-08977-w
OADOI: https://oadoi.org/10.1038/s41598-017-08977-w
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
1184 Genetics, developmental biology, physiology
Subjects:
Funding: The study was supported by Jane and Aatos Erkko Foundation (M.H., M.R.), The European Union Grant (Health H-FS-2009-223062; M.H., D.B., C.F.P.), The Academy of Finland (M.H.), The Sigrid Juselius Foundation (M.H.), Alma and K.A. Snellman Foundation (M.M., M.K.K., M.R.), Emil Aaltonen Foundation (M.K.K.), Foundation of Pediatric Research in Finland (M.K.K.), The Research Foundation of the Pulmonary Diseases (HES) (M.K.K.), the Competitive State Research Financing of the Tampere University Hospital (M.R.), the Competitive State Research Financing of the Oulu University Hospital (M.R.), The Programmes Hospitaliers de Recherche Clinique AOR 07 018 and AOM P100117, Assistance Publique–Hôpitaux de Paris, and Agence Nationale de la Recherche ANR-09-GENO-037 (AH), The British Columbia Lung Association (P.M.L.).
Dataset Reference: Electronic supplementary material:
  https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-017-08977-w/MediaObjects/41598_2017_8977_MOESM1_ESM.pdf
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