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

Kaartokallio T, Wang J, Heinonen S, Kajantie E, Kivinen K, Pouta A, Gerdhem P, Jiao H, Kere J, Laivuori H

Sci Rep 6 (-) 29085 [2016-07-07; online 2016-07-07]

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 (nā€‰=ā€‰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.

Bioinformatics Compute and Storage [Service]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

National Genomics Infrastructure [Service]

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PubMed 27384325

DOI 10.1038/srep29085

Crossref 10.1038/srep29085

pii: srep29085
pmc: PMC4935848