# Genomic, gene-environment and casual inference studies in diabetic complications

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $544,425

## Abstract

Over 34 million Americans (~10% of population) have diabetes, 90-95% of which is type 2
diabetes (T2D). T2D is a leading cause of health complications in the US, and minority
populations with diabetes are more likely to experience microvascular complications,
macrovascular disease, and subsequent death than their White counterparts even when access
to care is comparable. The pathophysiology of hyperglycemic organ damage, and why some
patients are relatively spared, remains largely unknown. Aggressive glycemic control is known
to decrease the frequency of diabetic complications, particularly microvascular, however, few
patients are able reach recommended glycemic targets. Inherited variation is known to
contribute to the risk of T2D complications. However, genetic associations studies of diabetic
complications have only recently begun to reveal the specific genes and pathways responsible
for increased susceptibility. While these findings show the promise of this approach, there is an
urgent need to better understand the mechanisms by which hyperglycemia leads to organ
damage and increase genetic discoveries in diabetic complications. To achieve this goal, we
hypothesize that genetics can further enhance the biological insights into diabetic complications
by using large-scale sample size, consideration of pleiotropy, environmental modulation and
genetic subtyping. The following Specific Aims are proposed to test this hypothesis 1) Genomic
and pleiotropy analyses of diabetic complications in 185K subjects with T2D across five racial-
ethnic groups; 2) Gene x environment (GxE) interaction analyses of diabetic complications to
consider the role of environmental modulation on genetic risk T2D complications in up to 1.3M
subjects with and without T2D; and 3) genetic risk profiles and causal inference in diabetic
complications to identify causal risk factors and disentangle the relationship between the factors
and T2D and its complications. This work has the potential to elucidate the mechanisms of
diabetic complications and provide insights into biology and knowledge critical to guide the
development of potential clinical predictors, strategies for prevention and guide development of
new therapies.

## Key facts

- **NIH application ID:** 10889182
- **Project number:** 5R01DK135868-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** RANY SALEM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $544,425
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889182

## Citation

> US National Institutes of Health, RePORTER application 10889182, Genomic, gene-environment and casual inference studies in diabetic complications (5R01DK135868-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10889182. Licensed CC0.

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