|
Academic/Biomedical Research
News & Jobs
|
|
|
|
|
|
|
|
|
|
|
|
|
Free Newsletters
Archive
My Subscriptions
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers
Regional News
US & Canada
Biotech Bay
Biotech Beach
Genetown
Pharm Country
BioCapital
BioMidwest
Bio NC
BioForest
Southern Pharm
BioCanada East
US Device
Europe
Asia
Company Profiles
Research Store
Research Events
Post an Event
Real Estate
Business Opportunities
|
|
|
|
PLoS By Category | Recent
PLoS Articles
|
|
Obstetrics
|
Genome-Wide Association Scan Identifies a Risk Locus for Preeclampsia on 2q14, Near the Inhibin, Beta B Gene
Published:
Wednesday, March 14, 2012
Author:
Matthew P. Johnson et al.
by 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
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 (r2?=?0.92), but not (r2<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 (r2>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).
More...
|
|
|
 |
|
|
|
|
|
|
|
|