Notice Number: NOT-DA-20-030
Release Date: March 5, 2020
First Available Due Date: une 05, 2020
Expiration Date: September 08, 2023
National Institute on Drug Abuse (NIDA)
This Notice encourages applications for research projects that identify, validate and/or functionally characterize loci, genetic variations and haplotypes that are associated with vulnerability to addiction and that potentially inform the likelihood of responsiveness to treatment. Data may be collected from the general population, special populations, recent admixed populations, and/or electronic medical records (EMR). Secondary data analysis of data collected from the general population, special populations, recent admixed populations, and/or animal models is also appropriate for this notice. Investigators are encouraged to include functional characterization, gene x gene interactions, gene x environment interactions, and gene x environment x development interactions.
Background and Research Objectives
The success of identifying genetic loci for nicotine and alcohol as well as for other complex genetic disorders has thus far been the result of the collection of large samples of people of European descent. Identification of genetic variants for cannabis and opioids are beginning to be discovered, but much larger samples are required to increase power to discover new variants and replicate these preliminary findings. Genome Wide Association Studies (GWAS) for cocaine and methamphetamine are currently underpowered for detecting genetic loci. Thus, applicants are encouraged to recruit new cohorts to increase sample size for Genome Wide Association Studies (GWAS) and whole genome wide sequencing studies for Opioid Use Disorder, Amphetamine Use Disorder, Cocaine Use Disorder, and Cannabis Use Disorder. Exposed controls are also needed for these studies. There are opportunities to increase sample sizes for genetic analysis of substance use disorder using electronic health records (EHR) in health care systems and biorepositories where participants are already genotyped.
Recruitment of individuals of non-European ancestry suffering from these disorders is also encouraged to assist in the identification of causal variants, ancestry specific variants, and to understand the role of genetic background in substance use phenotypes.
Applicants are encouraged to integrate functional genetic studies such as global and single cell gene expression analysis, expressed QTL analyses, epigenetic modifications, and higher order chromatin modifications in relevant tissues with genetic mapping studies. Functional genetic studies increase power by reducing the number of multiple comparisons and contribute to the functional significance of individual GWAS hits. Improved statistical methods are needed to layer these types of functional studies on GWAS data.
To augment underpowered GWAS studies of SUD, investigators are encouraged to explore the feasibility of integrating genetic data derived from genetic studies of substance use disorder-relevant phenotypes and behaviors in model organisms.
Given the complex phenotypes associated with substance use disorders and their comorbid conditions, we encourage the use of innovative genetic and statistical methods that incorporate epistasis, gene x gene, gene x environment and genetic pathway interactions to capture the etiology of these complex behaviors. When possible, we encourage the use of standard phenotypic measures when applicable to facilitate comparison of results among different studies. We also seek studies that balance detailed phenotypic documentation with sample size and feasibility.
Phenotype definition of case and control (exposed and unexposed) individuals is a central issue in the analysis of complex traits and is an essential component to applications responding to this Notice. Investigators are encouraged to use existing instruments that have been used by the NIDA Genetics Consortium, http://nidagenetics.org/ and browse through the study information links to access the instruments. In the case of using electronic health records there is a need to develop algorithms to derive diagnoses for substance use disorders.
Alternative phenotype definitions may better describe the genetic aspects of addiction. Therefore, investigators may propose to use other phenotypic information, such as the presence or absence of biological markers or exhibition of unique individual traits, as well as combinations of these and/or co-morbid conditions.
Examples of broad research topics include, but are not limited to:
Molecular genetics approaches:
In addition to encouraging the use core elements for phenotyping SUD (see research strategy section of this Notice), harmonizing demographic information and substance use history applicants may propose to:
Statistical genetics and computational approaches:
Applicants interested in studying gene-environment interactions should refer to (NOT-DA-19-038) Notice of Special Interest (NOSI): Gene-Environment Interplay in Substance Use Disorders (R01, R21)
Application and Submission Information
This notice applies to due dates on or after June 5, 2020 and subsequent receipt dates through September 8, 2023.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.
For funding consideration, applicants must include “NOT-DA-20-030” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
When preparing an application, researchers are strongly encouraged to present a rationale that carefully balances important substantive, methodological, and budgetary issues.
Applicants are encourage to use the phenotypes and phenotypes assessments for substance use in the Phenx Tool Kit to enable harmonization with other studies to increase power. https://www.phenxtoolkit.org/search/results?searchTerm=substance+abuse&searchtype=smartsearch and harmonize with previously funded studies (https://nidagenetics.org/)
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Jonathan D. Pollock, Ph.D.
National Institute on Drug Abuse (NIDA)