PLoS ONE (Jan 2012)

Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene.

  • Matthew P Johnson,
  • Shaun P Brennecke,
  • Christine E East,
  • Harald H H Göring,
  • Jack W Kent,
  • Thomas D Dyer,
  • Joanne M Said,
  • Linda T Roten,
  • Ann-Charlotte Iversen,
  • Lawrence J Abraham,
  • Seppo Heinonen,
  • Eero Kajantie,
  • Juha Kere,
  • Katja Kivinen,
  • Anneli Pouta,
  • Hannele Laivuori,
  • FINNPEC Study Group,
  • Rigmor Austgulen,
  • John Blangero,
  • Eric K Moses

DOI
https://doi.org/10.1371/journal.pone.0033666
Journal volume & issue
Vol. 7, no. 3
p. e33666

Abstract

Read online

Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10(-7), OR = 1.57; rs12711941, p = 4.26×10(-7), OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p0.92). We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes ±500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, ∼250 kb centromeric to INHBB, and preeclampsia (p = 0.03). We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s).