ELUCIDATING THE CAUSAL ASSOCIATIONS UNDERLYING ALZHEIMER'S DISEASE - PROJECT SUMMARY ALZHEIMERâS DISEASE…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
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ASST_NON_R00AG070109_075 · REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISC… · Department of Health and Human Services
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- Assistance award identifier
- ASST_NON_R00AG070109_075
- FAIN
- R00AG070109
- Recipient
- REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $870,432
- Period
- Feb 1, 2021 – Nov 30, 2025
- Fiscal year
- 2023
- Place of performance state
- CA
- Source file
- FY2023_All_Assistance_Full_20261006.zip
Description
ELUCIDATING THE CAUSAL ASSOCIATIONS UNDERLYING ALZHEIMER'S DISEASE - PROJECT SUMMARY ALZHEIMERâS DISEASE (AD) IS A GLOBAL CRISIS FACING THE AGING POPULATION AND SOCIETY AS A WHOLE. WITH THE NUMBER OF PEOPLE LIVING WITH AD PREDICTED TO RISE DRAMATICALLY IN THE COMING DECADES, IT IS IMPERATIVE TO PURSUE RESEARCH THAT AIMS TO REDUCE THE EXPECTED INCIDENCE OF DEMENTIA, SUCH AS IDENTIFYING MODIFIABLE RISK FACTORS FOR LIFESTYLE INTERVENTIONS. A PREREQUISITE TO ESTABLISHING LIFESTYLE INTERVENTIONS IS DEMONSTRATING A CAUSAL EFFECT OF THE PROPOSED EXPOSURE (A RISK FACTOR) ON AD OR AD ENDOPHENOTYPES. THE OVERARCHING OBJECTIVE OF THIS RESEARCH PROGRAM IS TO ENHANCE OUR UNDERSTANDING OF THE CAUSAL RELATIONSHIPS UNDERLYING ALZHEIMERâS DISEASE BY UTILIZING GENETICALLY INFORMED CAUSAL INFERENCE METHODS. WE WILL USE STATE-OF-THE-ART TECHNIQUES IN STATISTICAL GENETICS THAT EXPLOIT THE POLYGENIC RISK SCORING (PRS) AND MENDELIAN RANDOMIZATION (MR) APPROACHES. PRS PROVIDE AN ESTIMATE OF AN INDIVIDUAL'S GENETIC PROPENSITY TO A TRAIT AND CAN BE USED TO INFER GENETIC OVERLAP BETWEEN PHENOTYPES VIA PREDICTING ONE PHENOTYPE FROM THE PRS OF ANOTHER. THE FIRST AIM WILL IDENTIFY TRAITS THAT HAVE A SHARED GENETIC ETIOLOGY WITH AD OUTCOMES BY CONDUCTING A PHENOME-WIDE PRS ANALYSIS. THIS WILL PRIORITIZE PUTATIVE DISEASE-MODIFYING TRAITS FOR AD OUTCOMES. THE SECOND AIM WILL CONDUCT AN MR PHENOME-WIDE ASSOCIATION STUDY TO IDENTIFY NOVEL RISK FACTORS FOR AD THAT HAVE NOT BEEN IDENTIFIED USING PREVIOUS EPIDEMIOLOGICAL APPROACHES, WHILE PRIORITIZING HYPOTHESES IDENTIFIED IN THE CURRENT LITERATURE (E.G. VASCULAR HEALTH). MR USES GENETIC VARIANTS AS PROXIES FOR EXPOSURES TO PROVIDE AN ESTIMATE OF THE CAUSAL ASSOCIATION BETWEEN AN INTERMEDIATE EXPOSURE AND AN OUTCOME AND CONCEPTUALLY SIMILAR TO A âGENETIC RANDOMIZED CONTROL TRIALâ DUE TO THE RANDOM ALLOCATION OF GENOTYPES FROM PARENTS TO OFFSPRING. IN THE FINAL AIM, PRS AND MR WILL BE USED TO DETERMINE IF INDIVIDUAL RISK FACTORS DIFFERENTIALLY CO