# Context matters: Network modeling of COPD regulatory variants across tissues and exposures

> **NIH NIH K25** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $172,398

## Abstract

Project Abstract/Summary
The last decade has seen rapid progress in identifying genetic variants that confer disease risk. However, the
biological context in which these variants exert their influence is not fully understood. For example, cigarette
smoke is a major risk factor for chronic obstructive pulmonary disease (COPD); however, only a subset of
smokers develop COPD, suggesting that genetics may play a role in the pathogenesis of COPD. Genome-
wide association studies have identified more than twenty genetic loci associated with COPD status. However,
these single nucleotide polymorphisms (SNPs) only explain a small amount of the phenotypic variance of
COPD. This suggests that many variants of weak phenotypic effect work together to influence COPD
pathobiology.
 One of the challenges now for pulmonary geneticists is to understand how these many SNPs work together
to influence biological function, and to identify the contexts in which those functions are important. Given that
disease-associated SNPs often do not alter protein coding, these SNPs likely influence cellular phenotypes
through regulatory control of gene expression.
 We propose to develop new regulatory network models for modeling the collective effect of disease-
associated SNPs across tissues and on exposures such as cigarette smoke. We will then apply these methods
to better understand the context-specific regulatory function of variants associated with COPD.
 Dr. Platig’s training in physics, complex systems, and genomics has well prepared him to carry out this
research. However, additional training in statistical genetics, functional genomics, network theory, and
pulmonary biology will aid in his scientific and professional development as he starts his faculty position at the
Channing Division of Network Medicine (CDNM) in the summer of 2018. With a blend of formal coursework,
intensive workshops, and interdisciplinary mentoring, Dr. Platig will obtain the necessary skills to achieve his
goals.
 The CDNM and Harvard Medical School provide outstanding opportunities for research and training in the
systems genetics of pulmonary disease, with four teaching hospitals and two Harvard schools within a five
block radius. Dr. Platig will have access to extensive computing resources through his primary mentor, Dr.
Silverman, and through his co-mentor Dr. Quackenbush. In addition, Dr. Platig will attend regular meetings with
pulmonologists, statistical geneticists, and physicians to get regular feedback on his research and training. This
combination of research and training will prepare Dr. Platig for identifying and tackling the open challenges in
the systems genetics of pulmonary disease.

## Key facts

- **NIH application ID:** 9983153
- **Project number:** 5K25HL140186-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** John Platig
- **Activity code:** K25 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,398
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983153

## Citation

> US National Institutes of Health, RePORTER application 9983153, Context matters: Network modeling of COPD regulatory variants across tissues and exposures (5K25HL140186-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9983153. Licensed CC0.

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