Integrative omics of preeclampsia in TOPMED and maternal cardiovascular health

TOPMED 中子痫前期的综合组学和孕产妇心血管健康

基本信息

  • 批准号:
    10604382
  • 负责人:
  • 金额:
    $ 70.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-04-15 至 2026-03-31
  • 项目状态:
    未结题

项目摘要

Preeclampsia (PE), the development of new-onset hypertension and proteinuria after 20 weeks gestation, is a severe pregnancy-specific disorder mediated by the placenta that affects 5% of all pregnancies. Women with prior PE have an 2-4 fold increased lifetime risk of cardiovascular disease, including ischemic heart disease and stroke. The underlying etiology of PE remains poorly understood; consequently, predictive and therapeutic options remain limited. PE has a substantial heritable component estimated at 55-60%, with both maternal and fetal contributions, estimated at 30-35% and 20%, respectively. Progress in understanding PE genetics has lagged other disorders due to: the involvement of two genomes (maternal and fetal), disease heterogeneity, the exclusion of obstetric phenotypes from many large cohort studies, and the lack of PE collections of adequate sample size for power to identify genetic risk loci. Beyond genetics, profiling of PE using other omic strategies has identified transcriptomic, proteomic, and metabolomic alterations that precede disease. However, PE cohorts with multiple omics on the same well-phenotyped individuals are lacking. To address these challenges and advance understanding of PE pathophysiology, we propose to leverage TOPMed data in the “Boston-Colombia Collaborative Adverse Pregnancy Outcome study” which capitalizes on two large, multi-ethnic pregnancy cohorts, LIFECODES (Boston) and GenPE (Colombia). LIFECODES is an ongoing longitudinal pregnancy cohort (2009–present, N >3000 pregnancies, 152 PE cases) with maternal samples from each trimester of pregnancy and delivery samples. GenPE is a Colombian study (2000 – 2012, N = 3260 cases, 4331 controls) created to identify maternal and fetal genetic risk variants. Specifically, for this proposal, we will leverage TOPMed X01 funded whole genome sequencing (WGS) on the entire LIFECODES and GenPE cohorts, as well as in-depth multi-omic profiling (metabolic, circulating microparticle proteomic and transcriptomic) on all antepartum plasma samples in matched PE case-control samples within LIFECODES, expected to be available before the grant start date. We propose three specific aims. First, we will perform gene discovery for preeclampsia using common variant, rare variant, gene based and maternal-fetal interaction analyses. Second, we will leverage longitudinal in-depth multi-omic profiling on all antepartum plasma samples in matched PE case- control samples to identify molecular subtypes of PE and link these to known and novel genetic variants. Third, we will test if polygenic risk scores for PE, supplemented by longitudinal molecular and clinical phenotypes, predict maternal morbidity at delivery and future cardiovascular disease. Taken together, analysis of this multi- omics project of PE in TOPMed, together with replication in independent cohorts, will yield novel insights into the etiology of preeclampsia. As adverse pregnancy outcomes dramatically increase the risk of future cardiometabolic disease in affected women, improved mechanistic understanding of pregnancy-related disorders will enhance strategies for improving women’s health and preventing future cardiovascular disease.
先兆子痫(PE)是妊娠20周后新发高血压和蛋白尿的一种疾病

项目成果

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RICHA SAXENA其他文献

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{{ truncateString('RICHA SAXENA', 18)}}的其他基金

Long COVID as a putative subtype of chronic fatigue syndrome
长期新冠肺炎是慢性疲劳综合症的一种推定亚型
  • 批准号:
    10686215
  • 财政年份:
    2022
  • 资助金额:
    $ 70.48万
  • 项目类别:
Integrative omics of preeclampsia in TOPMED and maternal cardiovascular health
TOPMED 中子痫前期的综合组学和孕产妇心血管健康
  • 批准号:
    10418036
  • 财政年份:
    2022
  • 资助金额:
    $ 70.48万
  • 项目类别:
Genetics of chronotype and impact on metabolic disease
时间型遗传学及其对代谢疾病的影响
  • 批准号:
    9176615
  • 财政年份:
    2016
  • 资助金额:
    $ 70.48万
  • 项目类别:
Melatonin and Receptor Gene Variant: Linking Circadian System and Type 2 Diabetes
褪黑激素和受体基因变异:昼夜节律系统与 2 型糖尿病的联系
  • 批准号:
    9129655
  • 财政年份:
    2015
  • 资助金额:
    $ 70.48万
  • 项目类别:
Discovery of genes for sleep traits
发现睡眠特征基因
  • 批准号:
    8902257
  • 财政年份:
    2014
  • 资助金额:
    $ 70.48万
  • 项目类别:
Impact of MTNR1B and CRY2 variants on sleep circadian physiology and metabolism
MTNR1B 和 CRY2 变异对睡眠昼夜节律生理和代谢的影响
  • 批准号:
    7976592
  • 财政年份:
    2010
  • 资助金额:
    $ 70.48万
  • 项目类别:
Impact of MTNR1B and CRY2 variants on sleep circadian physiology and metabolism
MTNR1B 和 CRY2 变异对睡眠昼夜节律生理和代谢的影响
  • 批准号:
    8139804
  • 财政年份:
    2010
  • 资助金额:
    $ 70.48万
  • 项目类别:
Mitochondrial Variation and risk of T2DM
线粒体变异和 T2DM 风险
  • 批准号:
    6924607
  • 财政年份:
    2004
  • 资助金额:
    $ 70.48万
  • 项目类别:
Mitochondrial Variation and risk of T2DM
线粒体变异和 T2DM 风险
  • 批准号:
    6791954
  • 财政年份:
    2004
  • 资助金额:
    $ 70.48万
  • 项目类别:

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