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

Linlu Zhao; Elizabeth W Triche; Kyle M Walsh; Michael B Bracken; Audrey F Saftlas; Josephine Hoh; Andrew T Dewan

doi:10.1186/1471-2393-12-61

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

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

Linlu Zhao, Elizabeth W Triche, Kyle M Walsh, Michael B Bracken, Audrey F Saftlas, Josephine Hoh and Andrew T Dewan

BMC pregnancy and childbirth, Vol.12(1), pp.61-61

06/29/2012

DOI: 10.1186/1471-2393-12-61

PMCID: PMC3476390

PMID: 22748001

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Abstract

Background: 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.Methods: 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.Results: 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.Conclusions: 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. © 2012 Zhao et al.; licensee BioMed Central Ltd.

Copy-number variant

Genome-wide association study

Microarray analysis

Preeclampsia

Single nucleotide polymorphism

Details

Title: Subtitle: Genome-wide association study identifies a maternal copy-number deletion in PSG11 enriched among preeclampsia patients
Creators: Linlu Zhao - Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, USA
Elizabeth W Triche - Brown University
Kyle M Walsh - Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, USA
Michael B Bracken - University of Iowa
Audrey F Saftlas - University of Iowa
Josephine Hoh - Yale University
Andrew T Dewan - Yale University
Resource Type: Journal article
Publication Details: BMC pregnancy and childbirth, Vol.12(1), pp.61-61
DOI: 10.1186/1471-2393-12-61
PMID: 22748001
PMCID: PMC3476390
NLM abbreviation: BMC Pregnancy Childbirth
ISSN: 1471-2393
eISSN: 1471-2393
Publisher: BioMed Central
Language: English
Date published: 06/29/2012
Academic Unit: Epidemiology
Record Identifier: 9984364417602771

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