Master regulators of unexplained variation in disease risk

Active Project Grant Awarded Last action

Award ID
R01HG012444
Recipient
Awarding agency
Obligated
$19,206,322

Award facts

Assistance listing
93.310 Trans-NIH Research Support
Completion date 88% complete
Originally
Funding
  • $17,293,090.00 Federal
  • $1,913,232.00 Non-federal
Funding agency
Office of the Director National Institutes of Health, Department of Health and Human Services
Place of performance
Wyoming, MI 49503, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Precision medicine requires an understanding of the origins and molecular control over complex traits and disease. The field is largely driven by human genetics, which adheres to a 1918 dogma that phenotype is determined solely by genetics and the environment. Yet, evidence from monozygotic twins and isogenic animal models indicate that up to 50% of phenotypic variation across diverse physiological traits and diseases cannot be explained by genetics or environment - there is something `more' that is unique to each individual, and that cannot be determined by analyzing population-level mean effects. These findings also indicate that even if we did have `complete' genetic and environmental knowledge, a substantial portion of disease heterogeneity would remain unaccounted for. The operating hypothesis for this project is that a substantial fraction of unexplained disease heterogeneity reflects inherently probabilistic properties of the biological system that lead to fixed, deterministic, real biological variation. There is compelling evidence for an evolved molecular circuitry that controls phenotypic variability as a quantitative trait. Thus, understanding variability as a quantitative trait is essential to understanding the etiology of phenotypic diversity (in general) and an individual's disease potential (in particular). Here, we will begin to finally answer the precision medicine questions of: what is the normal or expected disease potential for me? And, what are the origins and regulatory controls of non-genetic, non- environmental phenotypic and disease variability in humans? The first steps towards addressing these questions and identifying mechanisms through which probabilistic processes lead to disease heterogeneity is to create a catalogue of putative variance regulators and genes; a phenotypic, epigenetic, and cellular variance atlas charting the landscape of probabilistic variation in an isogenic model system (mice); and, to demonstrate that the regulatory architecture of variance control is conserved between mouse and humans. If IT is true that a significant portion of unexplained disease heterogeneity is due to the molecular control of variability itself, then we will have uncovered an entirely new area of disease etiology that can be harnessed by the community to develop fundamentally new predictive, diagnostic, and therapeutic interventions, irrespective of the disease of interest.

Transactions

Action Federal Non-federal Date
Amendment $0 $0
Amendment $1,928,796 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $1,928,798 $0
Amendment $1,928,798 $0
Amendment $1,922,580 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $1,919,218 $0
Amendment $1,919,218 $0
Amendment $1,919,218 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $1,913,232 $0
Original award $1,913,232 $1,913,232
Show all 20

Subawards

Subrecipient Amount Awarded
Mainehealth Maine Medical Center Research Institute (MMCRI) is responsible for characterizing phenomes, identifying variance loci and genes, and quantitative statistical… $600,413
Northeastern University Northeastern University will be responsible for developing and implementing statistical methods for studying various heterogeneity and multimodality and its… $164,116
Grand Valley State University Develop machine learning algorithms for analysis of biobank-scale Genome-wide Association Study (GWAS) datasets from the UK Biobank and AllOfUs projects.… $55,390
Geisinger Clinic Dr. David Carey is responsible for providing access to the longitudinal DiscovEHR cohort data and biobanked samples in Years 3-5 of the project. In Years 1-2,… $81,412
Geisinger Clinic Dr. David Carey is responsible for providing access to the longitudinal DiscovEHR cohort data and biobanked samples in Years 3-5 of the project. In Years 1-2,… $81,412
Grand Valley State University The Grand Valley State University Principal Investigator/Project Director and other personnel listed in the proposal budget justification will carry out the… $55,390
Kobenhavns Universitet Dr. Loose and team at the University of Copenhagen will contribute to the big data analyses. Specifically, we will interrogate geneenvironment data for evidence… $27,671
Northeastern University Northeastern University will be responsible for developing and implementing statistical methods for studying various heterogeneity and multimodality and its… $164,116
Mainehealth Services Drs. Joseph Nadeau and Christine Lary at Maine Medical Center Research Institute (MMCRI) are collaborating investigators on the R01HG012444 entitled… $600,413

Quick answers

Who received award R01HG012444?

R01HG012444 was awarded to Van Andel Research Institute by National Human Genome Research Institute (National Institutes of Health) on September 22, 2021.

How much is award R01HG012444 worth?

$19,206,322 has been obligated on R01HG012444: $17,293,090 in federal funding and $1,913,232 in non-federal funding.

Which agency awarded R01HG012444?

National Human Genome Research Institute (National Institutes of Health) awarded R01HG012444, with funding from Office of the Director (National Institutes of Health).

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login