title: X-chromosomal maternal and fetal SNPs and the risk of spontaneous preterm delivery in a Danish/Norwegian genome-wide association study.
abstract: BACKGROUND
  Recent epidemiological studies suggest that the maternal genome is an important contributor to spontaneous preterm delivery (PTD). There is also a significant excess of males among preterm born infants, which may imply an X-linked mode of inheritance for a subset of cases. To explore this, we examined the effect of maternal and fetal X-chromosomal single nucleotide polymorphisms (SNPs) on the risk of PTD in two independent genome-wide association studies and one replication study.
  
  
  METHODS
  Participants were recruited from the Danish National Birth Cohort and the Norwegian Mother and Child cohort studies. Data from these two populations were first analyzed independently, and then combined in a meta-analysis. Overall, we evaluated 12,211 SNPs in 1,535 case-mother dyads and 1,487 control-mother dyads. Analyses were done using a hybrid design that combines case-mother dyads and control-mother dyads, as implemented in the Haplin statistical software package. A sex-stratified analysis was performed for the fetal SNPs. In the replication study, 10 maternal and 16 fetal SNPs were analyzed using case-parent triads from independent studies of PTD in the United States, Argentina and Denmark.
  
  
  RESULTS
  In the meta-analysis, the G allele at the maternal SNP rs2747022 in the FERM domain containing 7 gene (FRMD7) increased the risk of spontaneous PTD by 1.2 (95% confidence interval (CI): 1.1, 1.4). Although an association with this SNP was confirmed in the replication study, it was no longer statistically significant after a Bonferroni correction for multiple testing.
  
  
  CONCLUSIONS
  We did not find strong evidence in our data to implicate X-chromosomal SNPs in the etiology of spontaneous PTD. Although non-significant after correction for multiple testing, the mother's G allele at rs2747022 in FRMD7 increased the risk of spontaneous PTD across all populations in this study, thus warranting further investigation in other populations.
authors.affiliation: Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Solveig
authors.initials: S
authors.lastname: Myking
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boyd
authors.forename: Ronny
authors.initials: R
authors.lastname: Myhre
authors.forename: Bjarke
authors.initials: B
authors.lastname: Feenstra
authors.forename: Astanand
authors.initials: A
authors.lastname: Jugessur
authors.forename: Aase S
authors.initials: AS
authors.lastname: Devold Pay
authors.forename: Ingrid H G
authors.initials: IH
authors.lastname: Ostensen
authors.forename: Nils-Halvdan
authors.initials: NH
authors.lastname: Morken
authors.forename: Tamara
authors.initials: T
authors.lastname: Busch
authors.forename: Kelli K
authors.initials: KK
authors.lastname: Ryckman
authors.forename: Frank
authors.initials: F
authors.lastname: Geller
authors.forename: Per
authors.initials: P
authors.lastname: Magnus
authors.forename: Håkon K
authors.initials: HK
authors.lastname: Gjessing
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.forename: Bo
authors.initials: B
authors.lastname: Jacobsson
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D047928:Premature Birth / Q000453:epidemiology* / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult