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The genetic component of preeclampsia: A whole-exome sequencing study
Preeclampsia is a major cause of maternal and perinatal deaths. The aetiology of preeclampsia is largely unknown but a polygenetic component is assumed. To explore this hypothesis, we performed an in-depth whole-exome sequencing study in women with (cases, N = 50) and without (controls, N = 50) pree...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951572/ https://www.ncbi.nlm.nih.gov/pubmed/29758065 http://dx.doi.org/10.1371/journal.pone.0197217 |
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author | Hansen, Anette Tarp Bernth Jensen, Jens Magnus Hvas, Anne-Mette Christiansen, Mette |
author_facet | Hansen, Anette Tarp Bernth Jensen, Jens Magnus Hvas, Anne-Mette Christiansen, Mette |
author_sort | Hansen, Anette Tarp |
collection | PubMed |
description | Preeclampsia is a major cause of maternal and perinatal deaths. The aetiology of preeclampsia is largely unknown but a polygenetic component is assumed. To explore this hypothesis, we performed an in-depth whole-exome sequencing study in women with (cases, N = 50) and without (controls, N = 50) preeclampsia. The women were identified in an unselected cohort of 2,545 pregnant women based on data from the Danish National Patient Registry and the Medical Birth Registry. Matching DNA was obtained from a biobank containing excess blood from routine antenatal care visits. Novogene performed the whole-exome sequencing blinded to preeclampsia status. Variants for comparison between cases and controls were filtered in the Ingenuity Variant Analysis software. We applied two different strategies; a disease association panel approach, which included variants in single genes associated with established clinical risk factors for preeclampsia, and a gene panel approach, which included biological pathways harbouring genes previously reported to be associated with preeclampsia. Variant variability was compared in cases and controls at the level of biological processes, signalling pathways, and in single genes. Regardless of the applied strategy and the level of variability examined, we consistently found positive correlations between variant numbers in cases and controls (all R(2)s>0.88). Contrary to what was expected, cases carried fewer variants in biological processes and signalling pathways than controls (all p-values ≤0.02). In conclusion, our findings challenge the hypothesis of a polygenetic aetiology for preeclampsia with a common network of susceptibility genes. The greater genetic diversity among controls may suggest a protective role of genetic diversity against the development of preeclampsia. |
format | Online Article Text |
id | pubmed-5951572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-59515722018-05-25 The genetic component of preeclampsia: A whole-exome sequencing study Hansen, Anette Tarp Bernth Jensen, Jens Magnus Hvas, Anne-Mette Christiansen, Mette PLoS One Research Article Preeclampsia is a major cause of maternal and perinatal deaths. The aetiology of preeclampsia is largely unknown but a polygenetic component is assumed. To explore this hypothesis, we performed an in-depth whole-exome sequencing study in women with (cases, N = 50) and without (controls, N = 50) preeclampsia. The women were identified in an unselected cohort of 2,545 pregnant women based on data from the Danish National Patient Registry and the Medical Birth Registry. Matching DNA was obtained from a biobank containing excess blood from routine antenatal care visits. Novogene performed the whole-exome sequencing blinded to preeclampsia status. Variants for comparison between cases and controls were filtered in the Ingenuity Variant Analysis software. We applied two different strategies; a disease association panel approach, which included variants in single genes associated with established clinical risk factors for preeclampsia, and a gene panel approach, which included biological pathways harbouring genes previously reported to be associated with preeclampsia. Variant variability was compared in cases and controls at the level of biological processes, signalling pathways, and in single genes. Regardless of the applied strategy and the level of variability examined, we consistently found positive correlations between variant numbers in cases and controls (all R(2)s>0.88). Contrary to what was expected, cases carried fewer variants in biological processes and signalling pathways than controls (all p-values ≤0.02). In conclusion, our findings challenge the hypothesis of a polygenetic aetiology for preeclampsia with a common network of susceptibility genes. The greater genetic diversity among controls may suggest a protective role of genetic diversity against the development of preeclampsia. Public Library of Science 2018-05-14 /pmc/articles/PMC5951572/ /pubmed/29758065 http://dx.doi.org/10.1371/journal.pone.0197217 Text en © 2018 Hansen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hansen, Anette Tarp Bernth Jensen, Jens Magnus Hvas, Anne-Mette Christiansen, Mette The genetic component of preeclampsia: A whole-exome sequencing study |
title | The genetic component of preeclampsia: A whole-exome sequencing study |
title_full | The genetic component of preeclampsia: A whole-exome sequencing study |
title_fullStr | The genetic component of preeclampsia: A whole-exome sequencing study |
title_full_unstemmed | The genetic component of preeclampsia: A whole-exome sequencing study |
title_short | The genetic component of preeclampsia: A whole-exome sequencing study |
title_sort | genetic component of preeclampsia: a whole-exome sequencing study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951572/ https://www.ncbi.nlm.nih.gov/pubmed/29758065 http://dx.doi.org/10.1371/journal.pone.0197217 |
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