# Genetic & Social Determinants of Health: Center for Admixture Science and Technology

> **NIH NIH RM1** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $2,608,026

## Abstract

PROJECT SUMMARY
It is imperative to understand the underlying sources of the large health disparities among individuals from
different racial and ethnic groups living in the United States (US). Complex relationships between genetics and
social factors influence health outcomes. Approximately 33% of people in the US belong to an ethnic minority
group and ~12.5% live below the federal poverty line. Historical and recent mixing of Europeans, Native
Americans, Africans and Asians resulted in the US population having a relatively large number of admixed
individuals who carry ancestry from outside their self-identified race. The All of Us (AoU) Program and the Million
Veterans Program (MVP) include genetic, health and socioeconomic information on all participants, and
therefore provide an opportunity to identify factors contributing to health disparities. However, the AoU program
and MVP require their data to stay within local hosting sites, therefore conducting joint analyses on these cohorts
requires the development of algorithms that enable privacy-protecting distributed computing (i.e., without
revealing individual-level data). There are three important gaps in understanding genetic determinants of health:
1) most studies have been dominated by European individuals, and while they control for global ancestry, there
is no attempt to model the patchwork of local ancestry characteristic of admixed individuals; 2) GWAS are
primarily conducted using SNPs, while important sources of ancestry-specific genetic variation (tandem repeats
(TRs) and the major histocompatibility complex (MHC) interval) are not assayed; and 3) most GWAS do not
adjust for socioeconomic factors. The American College of Medical Genetics and Genomics (ACMG) has
published a list of medically actionable cancer and cardiovascular genes recommended for return of incidental
findings of pathogenic variants to reduce morbidity and mortality, but having minorities excluded from healthcare
follow up due to common barriers (e.g., language and access) makes it difficult to distinguish between the genetic
and socioeconomic factors that contribute to disparate health outcomes. The goal of the CAST (Center for
Admixture Science and Technology) program is to improve the clinical utility of genetic information for all
populations living in the US. In Aim 1, we will develop and apply multivariate models of disease risk prediction
that incorporate local ancestry, complex variants (TRs and HLA types). In Aim 2, we will conduct scalable
distributed computing using data from millions of individuals across the AoU and MVP compute enclaves. In Aim
3, we will develop new approaches to characterize phenotypes using electronic health records and surveys from
AoU and MVP, assess the impact of including social determinants of health in our models, and prospectively
evaluate them with new AoU and MVP participants. To achieve these goals, we assembled a highly
interdisciplinary group of researchers with expertis...

## Key facts

- **NIH application ID:** 10492767
- **Project number:** 5RM1HG011558-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** KELLY A FRAZER
- **Activity code:** RM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,608,026
- **Award type:** 5
- **Project period:** 2021-09-22 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492767

## Citation

> US National Institutes of Health, RePORTER application 10492767, Genetic & Social Determinants of Health: Center for Admixture Science and Technology (5RM1HG011558-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10492767. Licensed CC0.

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