title: Synonymous ABCA3 variants do not increase risk for neonatal respiratory distress syndrome.
abstract: OBJECTIVE
  To determine whether synonymous variants in the adenosine triphosphate-binding cassette A3 transporter (ABCA3) gene increase the risk for neonatal respiratory distress syndrome (RDS) in term and late preterm infants of European and African descent.
  
  
  METHODS
  Using next-generation pooled sequencing of race-stratified DNA samples from infants of European and African descent at ≥34 weeks gestation with and without RDS (n = 503), we scanned all exons of ABCA3, validated each synonymous variant with an independent genotyping platform, and evaluated race-stratified disease risk associated with common synonymous variants and collapsed frequencies of rare synonymous variants.
  
  
  RESULTS
  The synonymous ABCA3 variant frequency spectrum differs between infants of European descent and those of African descent. Using in silico prediction programs and statistical strategies, we found no potentially disruptive synonymous ABCA3 variants or evidence of selection pressure. Individual common synonymous variants and collapsed frequencies of rare synonymous variants did not increase disease risk in term and late-preterm infants of European or African descent.
  
  
  CONCLUSIONS
  In contrast to rare, nonsynonymous ABCA3 mutations, synonymous ABCA3 variants do not increase the risk for neonatal RDS among term and late-preterm infants of European or African descent.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. Electronic address: wambach_j@kids.wustl.edu.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wambach
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wegner
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
authors.forename: Hillary B
authors.initials: HB
authors.lastname: Heins
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO; Center for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, St. Louis, MO.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Druley
authors.affiliation: Center for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, St. Louis, MO.
authors.forename: Robi D
authors.initials: RD
authors.lastname: Mitra
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
authors.forename: Aaron
authors.initials: A
authors.lastname: Hamvas
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
authors.forename: F Sessions
authors.initials: FS
authors.lastname: Cole
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D044383:Black People / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D014644:Genetic Variation; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D012127:Respiratory Distress Syndrome, Newborn / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D044465:White People / Q000235:genetics
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters