Preeclampsia risk genes
Preeclampsia runs in families and it is now clearly established that, like many other common human diseases, there is a large genetic involvement in the risk of developing preeclampsia. However, the genetics are complex and not yet fully elucidated. The identification of genetic risk variation for common complex diseases is a current high priority for the provision of personalised medicine and genetic analysis of preeclampsia therefore continues to be a critically important focus of research effort in obstetric medicine.
In 2000, Prof Eric Moses along with Prof Shaun Brennecke and their multidisciplinary research team based at the Royal Womens Hospital in Melbourne published a seminal genome wide linkage scan for preeclampsia in a cohort of Australian and New Zealand preeclampsia families. On the strength of this family study, Moses, Brennecke and acclaimed USA statistical geneticist John Blangero obtained funding from the NIH to identify the risk genes that the linkage evidence obtained in these families pointed to. In a major international collaboration that also included investigators in Norway, the team identified the activin receptor gene ACVR2A and the endoplasmic reticulum aminopeptidase 2 gene ERAP2 as preeclampsia susceptibility genes.
There remains however missing heritability for preeclampsia and Prof Moses and his collaborators are continuing the search for susceptibility genes now taking full advantage of recent advances in genomic analysis, including whole genome sequencing, transcriptomics and methylomics.
This work is a collaborative effort between researchers at The University of Western Australia, Curtin University, University of Texas Rio Grande Valley (UTRGV), the Royal Women’s Hospital in Melbourne, the Norwegian University of Science and Technology and the University of Helsinki.
- NHRMC Project Grant 1053152 [2013-2015]: $553,795. “Identification of protein altering variants influencing preeclampsia risk”
CIA Eric Moses, CIB John Blangero, CIC Shaun Brennecke
- NIH Research Project 3R01HD049847-05S1 [2010-2011]: USD$735,903. “Identification of pre-eclampsia susceptibility genes”
PI Eric Moses
- NIH Research Project 1R01HD049847-01A2 [2006-2011]: USD$2,997,881. “Identification of pre-eclampsia susceptibility genes”
PI Eric Moses
- Yong, H. E. J., P. Murthi, S. P. Brennecke and E. K. Moses (2018). Genetic Approaches in Preeclampsia. In: Murthi P., Vaillancourt C. (eds) Preeclampsia. Methods in Molecular Biology, vol 1710. Humana Press, New York, NY. [pubmed]
- Yong, H. E., P. E. Melton, M. P. Johnson, K. A. Freed, B. Kalionis, P. Murthi, S. P. Brennecke, R. J. Keogh and E. K. Moses (2015). “Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes.” PLoS One 10(5): e0128230. [pubmed]
- Johnson, M. P., S. P. Brennecke, C. E. East, T. D. Dyer, L. T. Roten, J. M. Proffitt, P. E. Melton, M. H. Fenstad, T. Aalto-Viljakainen, K. Makikallio, S. Heinonen, E. Kajantie, J. Kere, H. Laivuori, R. Austgulen, J. Blangero and E. K. Moses (2013). “Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease.” Mol Hum Reprod 19(7): 423-437. [pubmed]
- Johnson, M. P., S. P. Brennecke, C. E. East, H. H. Goring, J. W. Kent, Jr., T. D. Dyer, J. M. Said, L. T. Roten, A. C. Iversen, L. J. Abraham, S. Heinonen, E. Kajantie, J. Kere, K. Kivinen, A. Pouta, H. Laivuori, R. Austgulen, J. Blangero and E. K. Moses (2012). “Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene.” PLoS One 7(3): e33666. [pubmed]
- Loset, M., S. B. Mundal, M. P. Johnson, M. H. Fenstad, K. A. Freed, I. A. Lian, I. P. Eide, L. Bjorge, J. Blangero, E. K. Moses and R. Austgulen (2011). “A transcriptional profile of the decidua in preeclampsia.” Am J Obstet Gynecol 204(1): 84 e81-27. [pubmed]
- Johnson, M. P., L. T. Roten, T. D. Dyer, C. E. East, S. Forsmo, J. Blangero, S. P. Brennecke, R. Austgulen and E. K. Moses (2009). “The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations.” Hum Genet 126(5): 655-666. [pubmed]
- Fitzpatrick, E., M. P. Johnson, T. D. Dyer, S. Forrest, K. Elliott, J. Blangero, S. P. Brennecke and E. K. Moses (2009). “Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia.” Mol Hum Reprod 15(3): 195-204. [pubmed]
- Roten, L. T., M. P. Johnson, S. Forsmo, E. Fitzpatrick, T. D. Dyer, S. P. Brennecke, J. Blangero, E. K. Moses and R. Austgulen (2009). “Association between the candidate susceptibility gene ACVR2A on chromosome 2q22 and pre-eclampsia in a large Norwegian population-based study (the HUNT study).” Eur J Hum Genet 17(2): 250-257. [pubmed]
- Johnson, M. P., E. Fitzpatrick, T. D. Dyer, J. B. Jowett, S. P. Brennecke, J. Blangero and E. K. Moses (2007). “Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach.” Mol Hum Reprod 13(1): 61-67. [pubmed]
- Moses, E. K., E. Fitzpatrick, K. A. Freed, T. D. Dyer, S. Forrest, K. Elliott, M. P. Johnson, J. Blangero and S. P. Brennecke (2006). “Objective prioritization of positional candidate genes at a quantitative trait locus for pre-eclampsia on 2q22.” Mol Hum Reprod 12(8): 505-512. [pubmed]
- Moses, E. K., J. A. Lade, G. Guo, A. N. Wilton, M. Grehan, K. Freed, A. Borg, J. D. Terwilliger, R. North, D. W. Cooper and S. P. Brennecke (2000). “A genome scan in families from Australia and New Zealand confirms the presence of a maternal susceptibility locus for pre-eclampsia, on chromosome 2.” Am J Hum Genet 67(6): 1581-1585. [pubmed]
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