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Multi-omic Predictors of Renal Function among HIV-infected Individuals of African Ancestry

非洲血统 HIV 感染者肾功能的多组学预测因子

基本信息

批准号：
10013809
负责人：
Vincent Charles Marconi
金额：
$ 70.53万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10013809
关键词：
AIDS-Associated Nephropathy AIDS/HIV problem Acquired Immunodeficiency Syndrome Affect African African American Aging Apolipoproteins Biological Biological Markers Biological Process Body mass index Chronic Disease Chronic Kidney Failure Clinical Cohort Studies Complication Cross-Sectional Studies DNA Methylation Data Development Diabetes Mellitus Diagnosis Disease Outcome End stage renal failure Environment Environmental Risk Factor Epigenetic Process Exposure to Filtration Future Gene Expression Genes Genetic Genetic Variation Genome Genomics Glomerular Filtration Rate HIV HIV Infections HIV-2 Human Hypertension Immune response Incidence Individual Infection Kidney Kidney Diseases Knowledge Life Expectancy Link Longevity Longitudinal Studies Measures Mediating Mediation Methods Modeling Modification Molecular Outcome Pathogenesis Pathology Pathway interactions Physiological Play Population Prevention Randomized Regimen Renal function Research Risk Risk Factors Risk stratification Role Site Structure of molecular layer of cerebellar cortex System Therapeutic Time Variant Veterans Viremia antiretroviral therapy biological systems cigarette smoking co-infection comorbidity design epigenetic marker epigenetic variation epigenome epigenome-wide association studies epigenomics experience functional genomics high risk human disease improved inter-individual variation kidney dysfunction longitudinal analysis mortality multiple omics novel outcome forecast precision medicine risk variant superinfection transcriptome transcriptome sequencing transcriptomics

项目摘要

PROJECT SUMMARY/ABSTRACT Although antiretroviral therapy (ART) results in successful suppression of HIV and a decrease of AIDS progression, people living with HIV (PLWH) experience a higher incidence of chronic diseases and shorter expectancy of life. Chronic kidney disease (CKD), which emerged as a common complication of both HIV infection and its treatment, has been a critical cause of shortened life span in PLWH. The pathogenesis of HIV- related CKD is multifactorial, linked to direct exposure to HIV viremia, superinfections, the systemic immune response to infection and ART regiments, as well as to traditional CKD risk factors. Both genetic and environmental factors play a role in the development and progression of CKD, and affect biological functions and pathways at multiple molecular levels. Research continues to suggest that epigenetic changes may play a pivotal role in the pathology of CKD and HIV infection. Integrated with other molecular layers, such as host genome and transcriptome, epigenome can mediate genetic, environmental and physiological effects, and can potentially influence kidney function. However, the epigenomic and multi-omic impacts on kidney function and disease have not been investigated at population level, particularly among people of African ancestry who experience high burden of CKD but underrepresented in multi-omics research. We will identify and replicate epigenetic predictors of kidney function using a longitudinal epigenome-wide approach (Aim 1). We will also examine genetic factors associated with epigenetics and kidney disease to elucidate mediation, modification and causal inference between genetics, DNAm and kidney function (Aim2). We will conduct integrative multi-omics analyses to genes, pathways and molecular system related to eGFR (Aim 3). Knowledge learned from this study will potentially improve long-term clinical outcomes of PLWH, promote precision medicine for HIV treatment, and support high priority topics in HIV/AIDS research.

项目总结/文摘