Genome-wide association study identifies a maternal copy-number deletion in <it>PSG11</it> enriched among preeclampsia patients
<p>Abstract</p> <p>Background</p> <p>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 et...
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| Format: | Article |
| Language: | English |
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BMC
2012-06-01
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| Series: | BMC Pregnancy and Childbirth |
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| Online Access: | http://www.biomedcentral.com/1471-2393/12/61 |
| _version_ | 1811265780775387136 |
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| author | Zhao Linlu Triche Elizabeth W Walsh Kyle M Bracken Michael B Saftlas Audrey F Hoh Josephine Dewan Andrew T |
| author_facet | Zhao Linlu Triche Elizabeth W Walsh Kyle M Bracken Michael B Saftlas Audrey F Hoh Josephine Dewan Andrew T |
| author_sort | Zhao Linlu |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 <it>a priori</it> that only deletions would be selected for assay on the entire case-control dataset using quantitative real-time PCR.</p> <p>Results</p> <p>The top four SNP candidates had an allelic or genotypic <it>p</it>-value between 10<sup>-5</sup> and 10<sup>-6</sup>, 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 <it>PSG11</it> gene contiguous to a highly plastic genomic region. All algorithm calls for these regions were assay confirmed.</p> <p>Conclusions</p> <p>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.</p> |
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| issn | 1471-2393 |
| language | English |
| last_indexed | 2024-04-12T20:30:06Z |
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| series | BMC Pregnancy and Childbirth |
| spelling | doaj.art-138c3082c6534fcaab2fbbf529a1cdce2022-12-22T03:17:45ZengBMCBMC Pregnancy and Childbirth1471-23932012-06-011216110.1186/1471-2393-12-61Genome-wide association study identifies a maternal copy-number deletion in <it>PSG11</it> enriched among preeclampsia patientsZhao LinluTriche Elizabeth WWalsh Kyle MBracken Michael BSaftlas Audrey FHoh JosephineDewan Andrew T<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 <it>a priori</it> that only deletions would be selected for assay on the entire case-control dataset using quantitative real-time PCR.</p> <p>Results</p> <p>The top four SNP candidates had an allelic or genotypic <it>p</it>-value between 10<sup>-5</sup> and 10<sup>-6</sup>, 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 <it>PSG11</it> gene contiguous to a highly plastic genomic region. All algorithm calls for these regions were assay confirmed.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2393/12/61Copy-number variantGenome-wide association studyMicroarray analysisPreeclampsiaSingle nucleotide polymorphism |
| spellingShingle | Zhao Linlu Triche Elizabeth W Walsh Kyle M Bracken Michael B Saftlas Audrey F Hoh Josephine Dewan Andrew T Genome-wide association study identifies a maternal copy-number deletion in <it>PSG11</it> enriched among preeclampsia patients BMC Pregnancy and Childbirth Copy-number variant Genome-wide association study Microarray analysis Preeclampsia Single nucleotide polymorphism |
| title | Genome-wide association study identifies a maternal copy-number deletion in <it>PSG11</it> enriched among preeclampsia patients |
| title_full | Genome-wide association study identifies a maternal copy-number deletion in <it>PSG11</it> enriched among preeclampsia patients |
| title_fullStr | Genome-wide association study identifies a maternal copy-number deletion in <it>PSG11</it> enriched among preeclampsia patients |
| title_full_unstemmed | Genome-wide association study identifies a maternal copy-number deletion in <it>PSG11</it> enriched among preeclampsia patients |
| title_short | Genome-wide association study identifies a maternal copy-number deletion in <it>PSG11</it> enriched among preeclampsia patients |
| title_sort | genome wide association study identifies a maternal copy number deletion in it psg11 it enriched among preeclampsia patients |
| topic | Copy-number variant Genome-wide association study Microarray analysis Preeclampsia Single nucleotide polymorphism |
| url | http://www.biomedcentral.com/1471-2393/12/61 |
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