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).
Johnson, M. P., Brennecke, S. P., East, C.
, Goring, H. H., Kent Jr, J. W., Dyer, T. D., ... Moses, E. K. (2012). Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin beta B gene
. PLoS ONE
(3), [e33666]. https://doi.org/10.1371/journal.pone.0033666