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Genomic and molecular characterization of preterm birth.
Knijnenburg, Theo A; Vockley, Joseph G; Chambwe, Nyasha; Gibbs, David L; Humphries, Crystal; Huddleston, Kathi C; Klein, Elisabeth; Kothiyal, Prachi; Tasseff, Ryan; Dhankani, Varsha; Bodian, Dale L; Wong, Wendy S W; Glusman, Gustavo; Mauldin, Denise E; Miller, Michael; Slagel, Joseph; Elasady, Summer; Roach, Jared C; Kramer, Roger; Leinonen, Kalle; Linthorst, Jasper; Baveja, Rajiv; Baker, Robin; Solomon, Benjamin D; Eley, Greg; Iyer, Ramaswamy K; Maxwell, George L; Bernard, Brady; Shmulevich, Ilya; Hood, Leroy; Niederhuber, John E.
Afiliación
  • Knijnenburg TA; Institute for Systems Biology, Seattle, WA 98109.
  • Vockley JG; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Chambwe N; Institute for Systems Biology, Seattle, WA 98109.
  • Gibbs DL; Institute for Systems Biology, Seattle, WA 98109.
  • Humphries C; Institute for Systems Biology, Seattle, WA 98109.
  • Huddleston KC; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Klein E; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Kothiyal P; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Tasseff R; Institute for Systems Biology, Seattle, WA 98109.
  • Dhankani V; Institute for Systems Biology, Seattle, WA 98109.
  • Bodian DL; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Wong WSW; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Glusman G; Institute for Systems Biology, Seattle, WA 98109.
  • Mauldin DE; Institute for Systems Biology, Seattle, WA 98109.
  • Miller M; Institute for Systems Biology, Seattle, WA 98109.
  • Slagel J; Institute for Systems Biology, Seattle, WA 98109.
  • Elasady S; Institute for Systems Biology, Seattle, WA 98109.
  • Roach JC; Institute for Systems Biology, Seattle, WA 98109.
  • Kramer R; Institute for Systems Biology, Seattle, WA 98109.
  • Leinonen K; Institute for Systems Biology, Seattle, WA 98109.
  • Linthorst J; Institute for Systems Biology, Seattle, WA 98109.
  • Baveja R; Fairfax Neonatal Associates, Inova Children's Hospital, Falls Church, VA 22042.
  • Baker R; Fairfax Neonatal Associates, Inova Children's Hospital, Falls Church, VA 22042.
  • Solomon BD; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Eley G; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Iyer RK; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Maxwell GL; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042.
  • Bernard B; Institute for Systems Biology, Seattle, WA 98109.
  • Shmulevich I; Institute for Systems Biology, Seattle, WA 98109.
  • Hood L; Institute for Systems Biology, Seattle, WA 98109; leroy.hood@systemsbiology.org john.niederhuber@inova.org.
  • Niederhuber JE; Inova Translational Medicine Institute, Inova Health System and Inova Fairfax Medical Center, Falls Church, VA 22042; leroy.hood@systemsbiology.org john.niederhuber@inova.org.
Proc Natl Acad Sci U S A ; 116(12): 5819-5827, 2019 03 19.
Article en En | MEDLINE | ID: mdl-30833390
Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. By using whole blood samples, we integrated whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation data for 270 PTB and 521 control families. We analyzed this combined dataset to identify genomic variants associated with PTB and secondary analyses to identify variants associated with very early PTB (VEPTB) as well as other subcategories of disease that may contribute to PTB. We identified differentially expressed genes (DEGs) and methylated genomic loci and performed expression and methylation quantitative trait loci analyses to link genomic variants to these expression and methylation changes. We performed enrichment tests to identify overlaps between new and known PTB candidate gene systems. We identified 160 significant genomic variants associated with PTB-related phenotypes. The most significant variants, DEGs, and differentially methylated loci were associated with VEPTB. Integration of all data types identified a set of 72 candidate biomarker genes for VEPTB, encompassing genes and those previously associated with PTB. Notably, PTB-associated genes RAB31 and RBPJ were identified by all three data types (WGS, RNA-seq, and methylation). Pathways associated with VEPTB include EGFR and prolactin signaling pathways, inflammation- and immunity-related pathways, chemokine signaling, IFN-γ signaling, and Notch1 signaling. Progress in identifying molecular components of a complex disease is aided by integrated analyses of multiple molecular data types and clinical data. With these data, and by stratifying PTB by subphenotype, we have identified associations between VEPTB and the underlying biology.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Nacimiento Prematuro Límite: Female / Humans / Male / Newborn Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2019 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Nacimiento Prematuro Límite: Female / Humans / Male / Newborn Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2019 Tipo del documento: Article