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Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth.

Publication ,  Journal Article
Hamvas, A; Feng, R; Bi, Y; Wang, F; Bhattacharya, S; Mereness, J; Kaushal, M; Cotten, CM; Ballard, PL; Mariani, TJ; PROP Investigators,
Published in: BMC Genet
October 20, 2018

BACKGROUND: Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings with genome-wide significance have been rare, and not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects with extremely divergent phenotypic outcomes could facilitate the identification of genetic variants or gene networks contributing disease risk. RESULTS: The Prematurity and Respiratory Outcomes Program (PROP) recruited a cohort of > 765 extremely preterm infants for the identification of markers of respiratory morbidity. We completed WES on 146 PROP subjects (85 affected, 61 unaffected) representing extreme phenotypes of early respiratory morbidity. We tested for association between disease status and individual common variants, screened for rare variants exclusive to either affected or unaffected subjects, and tested the combined association of variants across gene loci. Pathway analysis was performed and disease-related expression patterns were assessed. Marginal association with BPD was observed for numerous common and rare variants. We identified 345 genes with variants unique to BPD-affected preterm subjects, and 292 genes with variants unique to our unaffected preterm subjects. Of these unique variants, 28 (19 in the affected cohort and 9 in unaffected cohort) replicate a prior WES study of BPD-associated variants. Pathway analysis of sets of variants, informed by disease-related gene expression, implicated protein kinase A, MAPK and Neuregulin/epidermal growth factor receptor signaling. CONCLUSIONS: We identified novel genes and associated pathways that may play an important role in susceptibility/resilience for the development of lung disease in preterm infants.

Duke Scholars

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Published In

BMC Genet

DOI

EISSN

1471-2156

Publication Date

October 20, 2018

Volume

19

Issue

1

Start / End Page

94

Location

England

Related Subject Headings

  • Male
  • Infant, Premature
  • Infant, Newborn
  • Humans
  • Gestational Age
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Variation
  • Genetic Loci
  • Female
 

Citation

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Hamvas, A., Feng, R., Bi, Y., Wang, F., Bhattacharya, S., Mereness, J., … PROP Investigators, . (2018). Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth. BMC Genet, 19(1), 94. https://doi.org/10.1186/s12863-018-0679-7
Hamvas, Aaron, Rui Feng, Yingtao Bi, Fan Wang, Soumyaroop Bhattacharya, Jared Mereness, Madhurima Kaushal, et al. “Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth.BMC Genet 19, no. 1 (October 20, 2018): 94. https://doi.org/10.1186/s12863-018-0679-7.
Hamvas A, Feng R, Bi Y, Wang F, Bhattacharya S, Mereness J, et al. Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth. BMC Genet. 2018 Oct 20;19(1):94.
Hamvas, Aaron, et al. “Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth.BMC Genet, vol. 19, no. 1, Oct. 2018, p. 94. Pubmed, doi:10.1186/s12863-018-0679-7.
Hamvas A, Feng R, Bi Y, Wang F, Bhattacharya S, Mereness J, Kaushal M, Cotten CM, Ballard PL, Mariani TJ, PROP Investigators. Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth. BMC Genet. 2018 Oct 20;19(1):94.
Journal cover image

Published In

BMC Genet

DOI

EISSN

1471-2156

Publication Date

October 20, 2018

Volume

19

Issue

1

Start / End Page

94

Location

England

Related Subject Headings

  • Male
  • Infant, Premature
  • Infant, Newborn
  • Humans
  • Gestational Age
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Variation
  • Genetic Loci
  • Female