FINDING GENES FOR ALCOHOL-RELATED BEHAVIORS AND RISK FOR ALCOHOLISM

RELEASE DATE:  August 7, 2003

PA NUMBER:  PA-03-162

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. This announcement will stay active for 
only the May 1, 2006 AIDS and AIDS-related application submission date for these 
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms 
expires on the date indicated below. Other mechanisms relating to this announcement 
will continue to be accepted using paper PHS 398 applications until the stated 
expiration date below, or transition to electronic application submission. Parent 
R03 (PA-06-180) and R21 (PA-06-181) funding opportunity announcements have been 
issued for the submission date of June 1, 2006 and submission dates for AIDS and 
non-AIDS applications thereafter. Applications relating to R33 and R34 activities 
must be in response to NIH Institute/Center (IC)-specific announcements.

EXPIRATION DATE for R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006 
EXPIRATION DATE for All R01 Applications: August 1, 2006, unless reissued.
 
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
 (http://www.niaaa.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER: 93.273

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA 

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) solicits 
research proposals to identify and characterize genes that contribute to 
individual susceptibility to alcoholism and alcohol-related behaviors. This 
PA encourages multidisciplinary studies using advanced genetic and genomics 
technologies to find and characterize candidate genes in humans and animal 
models. 

RESEARCH OBJECTIVES

BACKGROUND

Genetic linkage and association studies have identified many chromosomal 
regions and quantitative trait loci (QTL) associated with complex phenotypes 
related to alcohol induced behaviors and/or alcoholism. However, the large 
number of genes residing in those previously identified chromosomal 
regions/QTLs remain undefined, due to the lack of the power and sensitivity 
of previously available methodology and technology. The completion of the 
sequences of the human and mouse genomes, and the development of new genomics 
technologies, have the potential for rapidly advancing the discovery of genes 
associated with alcoholism and alcohol-related behaviors. 

NIAAA seeks research applications that will explore and develop innovative 
computational, statistical, and molecular approaches to increase the power of 
gene discovery.  Areas of emphasis include utilizing advanced technologies 
such as high-throughput SNP genotyping, haplotype pattern mining, admixture 
linkage disequilbrium mapping, and DNA pooling for fine mapping.  Currently, 
haplotype maps for both human and mouse genomes are being developed and these 
maps will provide an additional resource for finding genes. 

Once fine mapping has further characterized a previously identified QTL or 
chromosomal region, candidate nucleotide variants within the locus can be 
identified.  Some methods that could be used for fine mapping include high-
throughput sequencing, RAGE, SAGE, DNA microarrays, protein arrays, and other 
high-throughput approaches. 

Many genes are predicted to reside within a QTL, and multiple polymorphisms 
are likely to be located in both coding and regulatory regions.  Functional 
tests of candidate genes are needed to determine if the polymorphism(s) or 
genetic variants are relevant to the alcohol-induced trait.  These tests may 
include the development of transgenic animals, such as BAC and YAC 
transgenics carrying chromosomal regions that contain large regulatory 
sequences.  

RESEARCH SCOPE

This PA specifically seeks applications that propose human or animal studies 
to identify and characterize genes associated with alcoholism and alcohol-
related behaviors.  Behaviors include alcohol consumption, 
tolerance/dependence, sensitivity/sedation, withdrawal, reinforcement, 
craving, and relapse.  Genes identified may be used to develop markers for 
alcohol vulnerability and dependence.  In addition, these genes may also be 
used to identify potential therapeutic targets and to predict individual 
responses to medications that treat alcoholism. Examples of research areas 
appropriate to this announcement include, but are not limited to: 

o   identification and characterization of genes associated with alcoholism and 
alcohol-related behaviors in the chromosomal regions previously identified in 
humans or animal models;

o   identification of genetic variants (SNPs/haplotpes) of associated with 
alcoholism and alcohol-related behaviors among the different populations, 
which will have high potential as targets for developing pharmacotherapeutic 
agents;  

o   discovery of new genes associated with alcoholism and alcohol-related 
behaviors and determination of functional relevance of the candidate genes 
and their polymorphic variants.

MECHANISM(S) OF SUPPORT 

This PA will use the NIH R01 and Exploratory/Developmental Research Grant 
(R21) award mechanisms 
(http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html).  
As an applicant, you will be solely responsible for planning, 
directing, and executing the proposed project.  Applications using the R21 
mechanism may request a project period of up to two years with a combined 
budget for direct costs of up to $275,000 for the two year period.  For 
example, the applicant may request $100,000 in the first year and $175,000 in 
the second year.  The request should be tailored to the needs of the project.  
Normally, no more than $200,000 may be requested in any single year.  

This PA uses just-in-time concepts. It also uses the modular as well as the 
non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format.  Otherwise follow the instructions for non-
modular research grant applications.  This program does not require cost 
sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.

Exploratory/developmental grant support is for new projects only; competing 
continuation applications will not be accepted. Two revisions of a previously 
reviewed exploratory/developmental grant application may be submitted as 
defined in NIH Policy at http://grants.nih.gov/grants/policy/amendedapps.htm.

ELIGIBLE INSTITUTIONS 

You may submit (an) application(s) if your institution has any of the 
following characteristics: 
   
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants. 

o Direct questions about genetic animal models and QTL mapping to:

Lisa A. Neuhold, Ph.D.
Program Director for Genetics
Genetics and Proteomics Research Branch
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 594-6228
Fax: (301) 594-0673
Email: Lneuhold@willco.niaaa.nih.gov

o Direct questions regarding human genetic studies to:

Zhaoxia Ren, M.D., Ph.D.
Program Director for Human Genetics
Genetics and Proteomics Research Branch
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 443-5733
Fax: (301) 594-0673
Email: zren@mail.nih.gov

o   Direct questions regarding functional genomics and proteomics to:

Q. Max Guo Ph.D.
Program Director 
Genetics and Proteomics Research Branch
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 443-0639
Fax: (301) 594-0673
Email: qmguo@mail.nih.gov

o Direct questions about financial or grants management matters to:

Judy Fox (formerly Simons)
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism 
6000 Executive Boulevard, Suite 504
Bethesda, MD 20892-7003
Telephone:  (301) 443-4704 
Fax:  (301) 443-3891 
E-mail: jsimons@willco.niaaa.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at http://grants.nih.gov/grants/dates.htm.  Application 
deadlines are also indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting 
up to $250,000 per year in direct costs must be submitted in a modular grant 
format.  The modular grant format simplifies the preparation of the budget in 
these applications by limiting the level of budgetary detail.  Applicants 
request direct costs in $25,000 modules.  Section C of the research grant 
application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: 
Applications requesting $500,000 or more in direct costs for any year must 
contact the proper program official identified above to receive authorization 
to submit the proposal. The applicant must include a cover letter identifying 
the NIAAA program official who has agreed to accept assignment of the 
application.   

Applicants requesting more than $500,000 must carry out the following steps:
   
1) Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your 
application for consideration for award; and,
  
3) Identify, in a cover letter sent with the application, the staff member 
and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types. Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be mailed on or before the receipt 
dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will not 
accept any application in response to this PA that is essentially the same as 
one currently pending initial review unless the applicant withdraws the 
pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude the 
submission of a substantial revision of an application already reviewed, but 
such application must include an Introduction addressing the previous 
critique.  

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  Appropriate scientific review groups 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score.
o Receive a second level review by an appropriate national advisory council 
or board.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning the application's overall score, weighting them as appropriate 
for each application.  The application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, an investigator may propose to 
carry out important work that by its nature is not innovative but is 
essential to move a field forward.

SIGNIFICANCE: Does this study address an important problem? If the aims of 
the application are achieved, how will scientific knowledge be advanced? What 
will be the effect of these studies on the concepts or methods that drive 
this field?

APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

INNOVATION: Does the project employ novel concepts, approaches or methods? 
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies?

INVESTIGATOR: Is the investigator appropriately trained and well suited to 
carry out this work? Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers (if any)?

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?  

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from genders, all racial and ethnic groups (and 
subgroups), and children as appropriate for the scientific goals of the 
research will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL CONSIDERATIONS 

DATA SHARING PLAN: DISSEMINATION OF DATA AND BIOLOGICAL MATERIALS
 
The sharing of biological materials, interview and other assessment data, and 
genotype information (including software) in a timely manner has been an 
essential element in the rapid progress that has been made in the genetic 
analysis of human diseases.  PHS policy is that investigators must make 
unique research resources readily available for research purposes to 
qualified individuals within the scientific community when first results 
based on these resources have been published (PRINCIPLES AND GUIDELINES FOR 
RECIPIENTS OF NIH RESEARCH GRANTS AND CONTRACTS ON OBTAINING AND 
DISSEMINATING BIOMEDICAL RESEARCH RESOURCES; published on December 23, 1999 
in the Federal Register) 
http://www.ott.nih.gov/policy/rt_guide_final.html.  
Accordingly, to address the interests of the research community and 
government in promoting the science of the genetic basis of alcohol abuse and 
alcoholism vulnerability, NIAAA expects applicants who respond to this PA to 
develop and propose detailed plans for sharing the data and materials 
generated through the grant.
 
It is expected that the Data Sharing Plan will specify the following 
elements: 1) creation of comprehensive and verified databases that contain 
all clinical, diagnostic, pedigree structure, and genotypic information 
collected and produced by the grant, 2) establishment of cell lines (from 
which DNA will be extracted and stored) from all protocol subjects from whom 
blood samples have been obtained, 3) a mechanism or protocol by which all 
databases and biological materials (DNA samples, cell lines) can be widely 
searched or distributed to qualified investigators in the scientific 
community, 4) a timetable specifying when various elements of the database 
(e.g., diagnostic, assessment, or genetic data) will be available for 
distribution.
 
BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to this PA will compete for available 
funds with all other recommended applications.  The following will be 
considered in making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research. This policy results from the NIH Revitalization Act of 1993 (Section 
492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s) for the hESC line(s) to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This PA 
is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


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