Abstract
Pre-eclampsia is a common vascular disorder of pregnancy. It originates in the placenta and targets the maternal endothelium. According to epidemiological research, >50% of the liability to this disorder can be accounted for by genetic factors. Both maternal and fetal genes contribute to the risk, but especially the fetal genetic risk profile is still poorly understood. We have previously detected linkage signals in multiplex Finnish families on chromosomes 2p25, 4q32, and 9p13 using maternal phenotypes. We performed a linkage analysis using updated maternal phenotypes and an unprecedented linkage analysis using fetal phenotypes. Markers genotyped were available from 237 individuals in 15 Finnish families, including 72 affected mothers and 49 affected fetuses. The MERLIN software was used for sample and marker quality control and linkage analysis. The results were compared against the original ones obtained by using the GENEHUNTER 2.1 software. The previous identification of the maternal susceptibility locus to a genetic location at 21.70 cM near marker D2S168 on chromosome 2 was confirmed by using both maternal and fetal phenotypes (maternal non-parametric linkage (NPL) score 3.79, P=0.00008, LOD (logarithm (base 10) of odds)=2.20 and fetal NPL score 2.95, P=0.002, LOD=1.71). As a novel finding, we present a suggestive linkage to chromosome 18 at 86.80 cM near marker D18S64 (NPL score 2.51, P=0.006, LOD=1.20) using the fetal phenotype. We propose that chromosome 18 may harbor a new fetal susceptibility locus for pre-eclampsia.
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Acknowledgements
We are indebted to all of the Finnish families whose participation made this work possible. We thank Leena Järvinen for technical assistance. This study was supported by grants from the Academy of Finland, the Research Funds of the University of Helsinki, the Government Special Subsidiary for Health Sciences (EVO funding) at Helsinki and Uusimaa Hospital District, the Helsingin Sanomat Centennial Foundation, the Jalmari and Rauha Ahokas Foundation, the Maud Kuistila Foundation, the Uusimaa Regional Fund of the Finnish Cultural Foundation, the Päivikki and Sakari Sohlberg Foundation, the Jane and Aatos Erkko Foundation and the Finnish Medical Foundation.
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Majander, K., Villa, P., Kivinen, K. et al. A follow-up linkage study of Finnish pre-eclampsia families identifies a new fetal susceptibility locus on chromosome 18. Eur J Hum Genet 21, 1024–1026 (2013). https://doi.org/10.1038/ejhg.2013.6
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DOI: https://doi.org/10.1038/ejhg.2013.6
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