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Genome-wide association study identifies a maternal copy-number deletion in PSG11 enriched among preeclampsia patients

Linlu Zhao1, Elizabeth W Triche2, Kyle M Walsh1, Michael B Bracken1, Audrey F Saftlas3, Josephine Hoh4 and Andrew T Dewan15*

Author Affiliations

1 Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA

2 Department of Epidemiology, Brown University School of Medicine, Providence, RI, USA

3 Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA

4 Division of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA

5 Division of Chronic Disease Epidemiology, Yale School of Public Health, 60 College Street, Room 403, New Haven, CT, 06520, USA

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BMC Pregnancy and Childbirth 2012, 12:61  doi:10.1186/1471-2393-12-61

Published: 29 June 2012



Specific genetic contributions for preeclampsia (PE) are currently unknown. This genome-wide association study (GWAS) aims to identify maternal single nucleotide polymorphisms (SNPs) and copy-number variants (CNVs) involved in the etiology of PE.


A genome-wide scan was performed on 177 PE cases (diagnosed according to National Heart, Lung and Blood Institute guidelines) and 116 normotensive controls. White female study subjects from Iowa were genotyped on Affymetrix SNP 6.0 microarrays. CNV calls made using a combination of four detection algorithms (Birdseye, Canary, PennCNV, and QuantiSNP) were merged using CNVision and screened with stringent prioritization criteria. Due to limited DNA quantities and the deleterious nature of copy-number deletions, it was decided a priori that only deletions would be selected for assay on the entire case-control dataset using quantitative real-time PCR.


The top four SNP candidates had an allelic or genotypic p-value between 10-5 and 10-6, however, none surpassed the Bonferroni-corrected significance threshold. Three recurrent rare deletions meeting prioritization criteria detected in multiple cases were selected for targeted genotyping. A locus of particular interest was found showing an enrichment of case deletions in 19q13.31 (5/169 cases and 1/114 controls), which encompasses the PSG11 gene contiguous to a highly plastic genomic region. All algorithm calls for these regions were assay confirmed.


CNVs may confer risk for PE and represent interesting regions that warrant further investigation. Top SNP candidates identified from the GWAS, although not genome-wide significant, may be useful to inform future studies in PE genetics.

Copy-number variant; Genome-wide association study; Microarray analysis; Preeclampsia; Single nucleotide polymorphism