title: Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis.
abstract: Previous studies have indicated that in adult smokers, a history of childhood pneumonia is associated with reduced lung function and chronic obstructive pulmonary disease. There have been few previous investigations using genome-wide association studies to investigate genetic predisposition to pneumonia. This study aims to identify the genetic variants associated with the development of pneumonia during childhood and over the course of the lifetime. Study subjects included current and former smokers with and without chronic obstructive pulmonary disease participating in the COPDGene Study. Pneumonia was defined by subject self-report, with childhood pneumonia categorized as having the first episode at <16 years. Genome-wide association studies for childhood pneumonia (843 cases, 9,091 control subjects) and lifetime pneumonia (3,766 cases, 5,659 control subjects) were performed separately in non-Hispanic whites and African Americans. Non-Hispanic white and African American populations were combined in the meta-analysis. Top genetic variants from childhood pneumonia were assessed in network analysis. No single-nucleotide polymorphisms reached genome-wide significance, although we identified potential regions of interest. In the childhood pneumonia analysis, this included variants in NGR1 (P = 6.3 × 10-8), PAK6 (P = 3.3 × 10-7), and near MATN1 (P = 2.8 × 10-7). In the lifetime pneumonia analysis, this included variants in LOC339862 (P = 8.7 × 10-7), RAPGEF2 (P = 8.4 × 10-7), PHACTR1 (P = 6.1 × 10-7), near PRR27 (P = 4.3 × 10-7), and near MCPH1 (P = 2.7 × 10-7). Network analysis of the genes associated with childhood pneumonia included top networks related to development, blood vessel morphogenesis, muscle contraction, WNT signaling, DNA damage, apoptosis, inflammation, and immune response (P ≤ 0.05). We have identified genes potentially associated with the risk of pneumonia. Further research will be required to confirm these associations and to determine biological mechanisms.
  
  
  
  NCT00608764.
authors: 1 Division of Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts.|2 Channing Division of Network Medicine and.
authors: Lystra P
authors: 0000-0001-6874-0097
authors: LP
authors: Hayden
authors: 2 Channing Division of Network Medicine and.|3 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Michael H
authors: MH
authors: Cho
authors: 2 Channing Division of Network Medicine and.
authors: Merry-Lynn N
authors: MN
authors: McDonald
authors: 4 National Jewish Health, Denver, Colorado; and.
authors: James D
authors: JD
authors: Crapo
authors: 5 Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland.
authors: Terri H
authors: TH
authors: Beaty
authors: 2 Channing Division of Network Medicine and.|3 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Edwin K
authors: EK
authors: Silverman
authors: 2 Channing Division of Network Medicine and.|3 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Craig P
authors: CP
authors: Hersh
mesh_terms: D002648:Child; D053263:Gene Regulatory Networks / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D011014:Pneumonia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
keywords: chronic obstructive pulmonary disease; genetic epidemiology; genome-wide association study; pediatrics; pneumonia