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Author (up) Johnson, M.P.; Brennecke, S.P.; East, C.E.; Goring, H.H.H.; Kent, J.W.J.; Dyer, T.D.; Said, J.M.; Roten, L.T.; Iversen, A.-C.; Abraham, L.J.; Heinonen, S.; Kajantie, E.; Kere, J.; Kivinen, K.; Pouta, A.; Laivuori, H.; Austgulen, R.; Blangero, J.; Moses, E.K. url  doi
  Title Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene Type Journal Article
  Year 2012 Publication PloS one Abbreviated Journal PLoS One  
  Volume 7 Issue 3 Pages e33666  
  Keywords Australia; Chromosomes, Human, Pair 2/*genetics; Cohort Studies; Computational Biology; Female; Finland; Gene Expression Regulation; Genetic Loci/*genetics; *Genetic Predisposition to Disease; Genome, Human/genetics; *Genome-Wide Association Study; Humans; Inhibin-beta Subunits/*genetics/metabolism; Norway; Polymorphism, Single Nucleotide/genetics; Pre-Eclampsia/*genetics; Pregnancy; Reproducibility of Results; Risk Factors; Sequence Analysis, DNA  
  Abstract 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 = 3.58x10(-7), OR = 1.57; rs12711941, p = 4.26x10(-7), OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p<5.11x10(-7)). These SNPs reside in an intergenic region less than 15 kb downstream from the 3' terminus of the Inhibin, beta B (INHBB) gene on 2q14.2. They are in linkage disequilibrium (LD) with each other (r(2) = 0.92), but not (r(2)<0.80) with any other genotyped SNP +/-250 kb. DNA re-sequencing in and around the INHBB structural gene identified an additional 25 variants. Of the 21 variants that we successfully genotyped back in the case-control cohort the most significant association observed was for a third intergenic SNP (rs7576192, p = 1.48x10(-7), OR = 1.59) in strong LD with the two significant GWAS SNPs (r(2)>0.92). 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, approximately 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).  
  Address Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America  
  Corporate Author FINNPEC Study Group Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:22432041; PMC3303857 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1534  
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