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Principal Investigator: Krzysztof Kiryluk
Organization: COLUMBIA UNIVERSITY HEALTH SCIENCES
Fiscal Year: 2024
Award: $805,207
Funding agency: National Human Genome Research Institute
PROJECT SUMMARY
Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality, with
a prevalence estimated at 13% in the U.S. that continues to increase annually. The etiology of CKD is complex,
with both genetic – including monogenetic and polygenic – and environmental contributions playing major roles.
African American and Hispanic communities in the U.S. are disproportionally affected by CKD; environmental,
socioeconomic, and inherited factors, such as APOL1 risk genotypes, are likely contributing to these disparities.
Multi-omic approaches including genetics, epigenetics, transcriptomics, proteomics, and metabolomics are high-
throughput technologies being leveraged for precision medicine that hold great potential to improve diagnosis
and clinical care for complex diseases such as CKD. As part of the Multi-omics Health and Disease Consortium,
this proposal will establish a Disease Study Site (DSS) focused on CKD. Our rationale for selecting CKD is three-
fold: 1) CKD has high cost and public health impact in the U.S. and disproportionally affects minority populations
underrepresented in genomic research; 2) CKD represents an important modifier of multi-omic profiles in other
common conditions; and 3) there is an urgent, unmet need to provide molecular disease subclassification in CKD
– and in particular non-diabetic CKD – as the current diagnosis relies solely on functional rather than molecular
criteria. Our hypothesis is that longitudinal blood and urine multi-omics can provide non-invasive means to better
subclassify non-diabetic CKD, and thus provide a new precision medicine-based approach for this condition. In
alignment with the mission of the consortium, our DSS also aims to address current disparities in kidney disease
and genomics, considering that individuals of non-European ancestry are overwhelming under-represented in
human genetic and multi-omic studies of kidney disease. To this end, we propose a prospective study of 200
CKD patients and 100 non-CKD controls of diverse ancestral backgrounds, with at least 75% of participants from
groups underrepresented in research. We will address the following questions: What are the molecular correlates
of longitudinal decline in renal function in ancestrally diverse patients? Are there specific molecular subtypes of
non-diabetic CKD identifiable by longitudinal multi-omics? What are the roles of environmental exposures, social
and economic stressors, and genetics in determining molecular CKD subtypes? Our team involves national
leaders in Precision Medicine and has a track record of successful execution of genetic, epidemiologic, and
interventional studies involving diverse underrepresented populations. We will coordinate efficient local
recruitment of our prospective cohort using innovative outreach methods that address barriers to recruiting
under-represented groups. Our long-term goal is to promote health equity and challenge the existing clinical
paradigms in CKD and multi-omics more broadly to advance precision medicine.
Terms: <APOL-I><APOL1><APOL1 gene><Acceleration><Address><Affect><African American><African American group><African American individual><African American people><African American population><African Americans><African ancestry><African descent><Afro American><Afroamerican><Anemia><Blood><Blood Reticuloendothelial System><Bone Diseases><Cancers><Cardiovascular Diseases><Caring><Causality><Chronic><Chronic Kidney Failure><Chronic Renal Disease><Chronic Renal Failure><Classification><Clinical><Complex><Data><Diabetes Mellitus><Diagnosis><Disease><Disorder><Disparities><Disparity><Ecologic Monitoring><Ecological Monitoring><Economic Factors><Economical Factors><Economics><Education><Educational aspects><Electrolytes><Ensure><Environment><Environmental Exposure><Environmental Monitoring><Environmental Toxin><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology><Epidemiology Research><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Equity><Ethics><Etiology><Exclusion><Exposure to><Filtration><Filtration Fractionation><Frequencies><Genetic><Genetic predisposing factor><Genetic study><Genomics><Glomerular Filtration Rate><Goals><Health><Heritability><Hispanic><Hispanic Populations><Hispanic group><Hispanic individual><Hispanic people><Hispanics><Histologic><Histologically><Human Genetics><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immunes><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Individual><Individuals from minority><Individuals of minority><Injury><Injury to Kidney><Intermediary Metabolism><Intervention Studies><Kidney Diseases><Lead><Leadership><Life><Lupus><Malignant Neoplasms><Malignant Tumor><Metabolic Processes><Metabolic dysfunction><Metabolism><Methods><Minority><Minority Groups><Minority People><Minority Population><Minority individual><Mission><Molecular><Molecular Disease><Morbidity><Morbidity - disease rate><NIH><National Institutes of Health><Nephrology><Nephropathy><Nephrotoxic><Outcome><Participant><Patients><Pattern><Pb element><Phenotype><Play><Population Heterogeneity><Position><Positioning Attribute><Prevalence><Prospective Studies><Prospective cohort><Proteomics><Protocol><Protocols documentation><Public Health><Renal Disease><Renal function><Reproducibility of Findings><Reproducibility of Results><Research><Research Design><Risk><Risk-associated variant><Role><Science><Site><Socioeconomic Factors><Standardization><Study Type><Systematics><Systemic disease><Toxic Environmental Agents><Toxic Environmental Substances><Toxicant exposure><Underrepresented Ethnic Minority><Underrepresented Groups><Underrepresented Minority><Underrepresented Populations><United States National Institutes of Health><Urine><Work><bone disorder><burden of disease><burden of illness><cardiovascular disorder><causation><chronic kidney disease><clinical care><co-morbid><co-morbidity><cohort><comorbidity><cost><design><designing><diabetes><disease burden><disease causation><disease control><disease risk><disease subgroups><disease subtype><disorder control><disorder risk><disorder subtype><diverse populations><economic><environmental testing><environmental toxicant><epidemiologic><epidemiologic investigation><epidemiological><epidemiology study><epigenetically><ethical><experience><expression subtypes><gene testing><gene-based testing><genetic predictors><genetic risk factor><genetic testing><health equity promotion><heavy metal Pb><heavy metal lead><heterogeneous population><high risk><high throughput technology><hispanic community><improved><inherited factor><injuries><innovate><innovation><innovative><intervention research><interventional research><interventional study><interventions research><kidney biopsy><kidney disorder><kidney dysfunction><kidney function><kidney injury><kidney toxicity><malignancy><metabolism measurement><metabolomics><metabonomics><molecular biomarker><molecular marker><molecular sub-types><molecular subsets><molecular subtypes><mortality><multidisciplinary><multiomics><multiple omics><neoplasm/cancer><nephrotoxicity><non-diabetic><nondiabetic><novel><outreach><panomics><pollutant><population diversity><precision medicine><precision-based medicine><promote health equity><prospective><recruit><renal biopsy><renal disorder><renal dysfunction><renal injury><risk allele><risk gene><risk genotype><risk loci><risk locus><risk variant><social><social factors><social health determinants><social role><socio-economic factors><statistics><stressor><study design><support network><toxic exposure><transcriptomics><under representation of groups><under represented groups><under represented people><under represented populations><under-representation of minorities><under-represented minority><underrepresentation of groups><underrepresentation of minorities><underrepresented people>