# Investigating causality between abnormalities of mineral metabolism and kidney, cardiovascular and bone disease

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $382,500

## Abstract

Abnormalities in mineral metabolism have consistently been associated with cardiovascular and bone disease,
among individuals with chronic kidney disease and in the general population. However, it is unknown whether
mineral metabolism biomarkers themselves represent causal processes for complications, how kidney function
impacts these processes, and which biomarker, if any, may be the most promising interventional target.
Mendelian Randomization (MR) employs genetic variants as unconfounded proxies of an exposure of interest
to estimate its causal effect on an outcome. We have now revealed genetic variants robustly associated with
circulating levels of mineral metabolism markers and will employ these findings, within the framework of MR, to
advance knowledge of the causal roles of mineral metabolism marker in cardiovascular and bone disease.
Recent developments in MR methods can also enable us to examine interactions and uncover heterogeneity of
treatment effect or efficacy of new therapies. MR can provide critical evidence to prioritize further research and
clinical applications, or just as importantly, to discourage additional resource allocation towards non-causal
pathways. The goal of this application is to comprehensively evaluate causal relationships between mineral
metabolites, kidney function, treatment strategies and clinical and subclinical phenotypes of cardiovascular
and bone disease.
We will conduct analyses using genomic data, based on Mendelian Randomization techniques, and will
leverage publicly available genome-wide association data and two of the largest practice-based biobanks in
the world: Vanderbilt’s BioVU and the Million Veteran Program (MVP). Using novel techniques and resources,
we will 1) evaluate the causal effect of mineral metabolites on cardiovascular and bone disease; 2) investigate
the interplay of kidney function in these associations; and 3) assess the likely effect of commonly prescribed
medications and potential drug targets on cardiovascular and bone events in chronic kidney disease. Together,
these complementary approaches will improve understanding of pathologies related to mineral metabolism
disturbances and will provide a launch point for the identification of novel drugs and therapies to prevent
cardiovascular and bone disease.

## Key facts

- **NIH application ID:** 10225394
- **Project number:** 5R01DK122075-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Cassianne Robinson-Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2019-07-16 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225394

## Citation

> US National Institutes of Health, RePORTER application 10225394, Investigating causality between abnormalities of mineral metabolism and kidney, cardiovascular and bone disease (5R01DK122075-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225394. Licensed CC0.

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