Genome-Wide Association Scan Identifies a Risk Locus for Preeclampsia on 2q14, Near the Inhibin, Beta B Gene
Year: 2012
Type: article
Study design: Observational Study
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 = 3.58×10(-7), OR = 1.57; rs12711941, p = 4.26×10(-7), OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p<5.11×10(-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 = 1.48×10(-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, ∼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).
Source: PLoS ONE
Authors: 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, for the FINNPEC Study Group, Rigmor Austgulen, John Blangero, Eric K. Moses
Institutions: Texas Biomedical Research Institute, Royal Women's Hospital, The University of Melbourne, Norwegian University of Science and Technology, The University of Western Australia, University of Eastern Finland, Kuopio University Hospital, University of Helsinki, Finnish Institute for Health and Welfare, Helsinki Children's Hospital, Science for Life Laboratory, Karolinska Institutet, Folkhälsans Forskningscentrum, Wellcome Sanger Institute
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: American Heart Association, Helsingin Yliopisto, Helsingin ja Uudenmaan Sairaanhoitopiiri, Texas Biomedical Research Institute, University of Melbourne, Jane ja Aatos Erkon Säätiö, Kuopion Yliopistollinen Sairaala, Novo Nordisk, Emil Aaltosen Säätiö, Norges Forskningsråd, Lastentautien Tutkimussäätiö, Tays, National Institutes of Health, Norwegian Institute of Public Health, National Institute of Mental Health, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2084017024