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Sci Rep. 2016 Jul 7;6:29085. doi: 10.1038/srep29085.

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

Author information

1
Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
2
Department of Biosciences and Nutrition, and Science for Life Laboratory, Karolinska Institutet, SE-141 83 Stockholm, Sweden.
3
Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
4
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
5
Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
6
PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
7
Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
8
Department of Government services, National Institute for Health and Welfare, Helsinki, Finland.
9
Department of Orthopedics, Karolinska University Hospital, Stockholm, Sweden.
10
Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden.
11
Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.
12
Folkhälsan Institute of Genetics, Helsinki, Finland.
13
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.

Abstract

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.

PMID:
27384325
PMCID:
PMC4935848
DOI:
10.1038/srep29085
[Indexed for MEDLINE]
Free PMC Article

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