In the post genome era, biological research and genomic medicine have been transformed by high-throughput technologies. New techniques have enabled researchers to investigate biological systems in great detail. Nonetheless, the extraordinary amount of information in the large number of emerging high-dimension datasets has not been fully exploited. Increasingly, pathway analysis and other a priori biological knowledge based approaches have improved success in extraction of valuable information from high-throughput experiments and genome-wide association studies. Preeclampsia is a complex disease and one of the most common causes of fetal and maternal morbidity and mortality worldwide. It is one of the great but enigmatic health problems. Despite many studies, there has been little fundamental improvement in our understanding in decades. It is a multi-system hypertensive disorder of pregnancy, characterized by variable degrees of maternal symptoms including elevated blood pressure, proteinuria and fetal growth retardation that affects 2-8 % of deliveries in the US. Many clinicians believe there is a difference between mild and severe or early and late preeclampsia. However, to date there is little direct evidence that they represent different genetic ideologies. We hypothesize that preeclampsia is a complex, polygenic disorder that entails activation of a network of genes. We further hypothesize that rare variants in the genes that contribute to the risk of preeclampsia can be identified using new bioinformatic approaches coupled with high-throughput technologies applied to appropriate cohorts of patients. We propose novel computational approaches to identify relevant genes and high-throughput technologies on appropriately selected patients that will help to identify the genetic architecture of this a multifactorial, polygenic disease.

Public Health Relevance

Preeclampsia is a multi-system hypertensive disorder of pregnancy, which affects 2-8 % of deliveries in the US. Preeclampsia is one of the most common causes of fetal and maternal morbidity and mortality worldwide. We will investigate the genetic architecture of severe preeclampsia by combining bioinformatics approaches and high-throughput technologies where will be applied to appropriate cohorts of patients.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brown University
United States
Zip Code
Bryner, Darshan; Criscione, Stephen; Leith, Andrew et al. (2017) GINOM: A statistical framework for assessing interval overlap of multiple genomic features. PLoS Comput Biol 13:e1005586
Cabral, Damien J; Wurster, Jenna I; Flokas, Myrto E et al. (2017) The salivary microbiome is consistent between subjects and resistant to impacts of short-term hospitalization. Sci Rep 7:11040
Nakka, Priyanka; Archer, Natalie P; Xu, Heng et al. (2017) Novel Gene and Network Associations Found for Acute Lymphoblastic Leukemia Using Case-Control and Family-Based Studies in Multiethnic Populations. Cancer Epidemiol Biomarkers Prev 26:1531-1539
Gamradt, Pia; Xu, Yun; Gratz, Nina et al. (2016) The Influence of Programmed Cell Death in Myeloid Cells on Host Resilience to Infection with Legionella pneumophila or Streptococcus pyogenes. PLoS Pathog 12:e1006032
Criscione, Steven W; Teo, Yee Voan; Neretti, Nicola (2016) The Chromatin Landscape of Cellular Senescence. Trends Genet 32:751-761
Sugden, Lauren Alpert; Ramachandran, Sohini (2016) Integrating the signatures of demic expansion and archaic introgression in studies of human population genomics. Curr Opin Genet Dev 41:140-149