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Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants

Pre-eclampsia is a common pregnancy disorder that is a major cause for maternal and perinatal mortality and morbidity. Variants predisposing to pre-eclampsia might be under negative evolutionary selection that is likely to keep their population frequencies low. We exome sequenced samples from a hund...

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Autores principales: Kaartokallio, Tea, Wang, Jingwen, Heinonen, Seppo, Kajantie, Eero, Kivinen, Katja, Pouta, Anneli, Gerdhem, Paul, Jiao, Hong, Kere, Juha, Laivuori, Hannele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935848/
https://www.ncbi.nlm.nih.gov/pubmed/27384325
http://dx.doi.org/10.1038/srep29085
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author Kaartokallio, Tea
Wang, Jingwen
Heinonen, Seppo
Kajantie, Eero
Kivinen, Katja
Pouta, Anneli
Gerdhem, Paul
Jiao, Hong
Kere, Juha
Laivuori, Hannele
author_facet Kaartokallio, Tea
Wang, Jingwen
Heinonen, Seppo
Kajantie, Eero
Kivinen, Katja
Pouta, Anneli
Gerdhem, Paul
Jiao, Hong
Kere, Juha
Laivuori, Hannele
author_sort Kaartokallio, Tea
collection PubMed
description Pre-eclampsia is a common pregnancy disorder that is a major cause for maternal and perinatal mortality and morbidity. Variants predisposing to pre-eclampsia might be under negative evolutionary selection that is likely to keep their population frequencies low. We exome sequenced samples from a hundred Finnish pre-eclamptic women in pools of ten to screen for low-frequency, large-effect risk variants for pre-eclampsia. After filtering and additional genotyping steps, we selected 28 low-frequency missense, nonsense and splice site variants that were enriched in the pre-eclampsia pools compared to reference data, and genotyped the variants in 1353 pre-eclamptic and 699 non-pre-eclamptic women to test the association of them with pre-eclampsia and quantitative traits relevant for the disease. Genotypes from the SISu project (n = 6118 exome sequenced Finnish samples) were included in the binary trait association analysis as a population reference to increase statistical power. In these analyses, none of the variants tested reached genome-wide significance. In conclusion, the genetic risk for pre-eclampsia is likely complex even in a population isolate like Finland, and larger sample sizes will be necessary to detect risk variants.
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spelling pubmed-49358482016-07-08 Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants Kaartokallio, Tea Wang, Jingwen Heinonen, Seppo Kajantie, Eero Kivinen, Katja Pouta, Anneli Gerdhem, Paul Jiao, Hong Kere, Juha Laivuori, Hannele Sci Rep Article Pre-eclampsia is a common pregnancy disorder that is a major cause for maternal and perinatal mortality and morbidity. Variants predisposing to pre-eclampsia might be under negative evolutionary selection that is likely to keep their population frequencies low. We exome sequenced samples from a hundred Finnish pre-eclamptic women in pools of ten to screen for low-frequency, large-effect risk variants for pre-eclampsia. After filtering and additional genotyping steps, we selected 28 low-frequency missense, nonsense and splice site variants that were enriched in the pre-eclampsia pools compared to reference data, and genotyped the variants in 1353 pre-eclamptic and 699 non-pre-eclamptic women to test the association of them with pre-eclampsia and quantitative traits relevant for the disease. Genotypes from the SISu project (n = 6118 exome sequenced Finnish samples) were included in the binary trait association analysis as a population reference to increase statistical power. In these analyses, none of the variants tested reached genome-wide significance. In conclusion, the genetic risk for pre-eclampsia is likely complex even in a population isolate like Finland, and larger sample sizes will be necessary to detect risk variants. Nature Publishing Group 2016-07-07 /pmc/articles/PMC4935848/ /pubmed/27384325 http://dx.doi.org/10.1038/srep29085 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kaartokallio, Tea
Wang, Jingwen
Heinonen, Seppo
Kajantie, Eero
Kivinen, Katja
Pouta, Anneli
Gerdhem, Paul
Jiao, Hong
Kere, Juha
Laivuori, Hannele
Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants
title Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants
title_full Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants
title_fullStr Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants
title_full_unstemmed Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants
title_short Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants
title_sort exome sequencing in pooled dna samples to identify maternal pre-eclampsia risk variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935848/
https://www.ncbi.nlm.nih.gov/pubmed/27384325
http://dx.doi.org/10.1038/srep29085
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