This Program Announcement expires on July 1, 2003, unless reissued.


Release Date:  June 27, 2000

PA NUMBER:  PA-00-115

National Institute on Drug Abuse



This Program Announcement (PA) seeks investigator-initiated applications for 
research projects that identify chromosomal loci and genetic variation in 
genes that are associated with increased vulnerability to addiction or 
dependence on stimulants (e.g., cocaine and amphetamine), narcotics (e.g., 
opiates), nicotine, benzodiazepines, barbiturates, cannabis, hallucinogens, 
and/or multiple drugs of abuse in human beings.  Thus, applications examining 
the genetics of addiction vulnerability to both illicit and legal drugs of 
abuse are relevant to this PA. 

This program announcement is a continuation of the program initiated by RFA 
DA-99-003, "Genetics of Drug Addiction Vulnerability,"  For other 
NIDA funding opportunities in genetics see the NIDA Genetics Workgroup 

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, Genetics of Drug 
Addiction Vulnerability, is related to one or more of the priority areas.  
Potential applicants may obtain a copy of "Healthy People 2010" at


Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government.  Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as principal 

The collection of clinically well characterized samples of sufficient size 
for linkage analyses and for linkage disequilibrium mapping studies in 
genetically isolated populations may be facilitated by the establishment of 
international consortia.  Collaborations among U.S. scientists and scientists 
at foreign institutions are encouraged, when scientifically appropriate.  In 
these cases, awards may be made to foreign institutions or to domestic 
applications that include foreign components.  Foreign institutions are not 
eligible for program project (P01) grants.


This PA will use the National Institutes of Health (NIH) regular research 
project (R01) grant, and a program project (P01) grant mechanism.  The P01 
mechanism supports broadly based multidisciplinary research programs that 
have a well defined, central research focus or objective.  The P01 consists 
of a minimum of three interrelated individual research projects that 
contribute to the overall program objective.  To achieve sufficient 
statistical power or needed expertise these projects may be located at more 
than one institution.  This type of award can also provide support for 
certain shared resources (“cores”) that provide funds for tasks common to two 
or more projects within the award.  NIH limits the time period for P01 grants 
to 5 years.  Modular instructions apply only to R01 applications.

The cover letter and abstract should indicate the type of mechanism for which 
the applicant is applying.  Specific information on individual research 
mechanisms can be obtained from the NIDA web site for funding information at

Because the nature and scope of the research proposed in response to this PA 
may vary, it is anticipated that the size of an award will also vary.  
Responsibility for the planning, direction, and execution of the proposed 
project will be solely that of the applicant.  



Evidence from adoption and twin studies, from genetic strains of rodents, and 
from induced mutations in mice, suggests that heritability may play a role in 
vulnerability to addiction.  The genetic variants underlying increased 
vulnerability to drug addiction are  unknown.  However, new scientific 
opportunities may now make it possible to identify and characterize the 
genetic variants that contribute to addiction vulnerability.  This knowledge 
will improve diagnosis, prevention, and treatment of drug addiction.  By 
better understanding the genetic factors involved in the addiction process, 
the environmental contributions to this disease can also be better 

Recent advances in statistical genetics, molecular biology, and genomic 
approaches have greatly accelerated the ability to identify the etiology of 
diseases that have a genetic basis.  The power of the genetic approach for 
neuroscience is evidenced by the recent positional cloning of genetic 
variations associated with many cases of Alzheimer"s disease and rare forms 
of Parkinson"s disease.  Animal models of these genetic disorders are now 
being created using transgenic technology.  These models provide a greater 
understanding of the underlying biology of the disease.  These and related 
approaches are likely to have applicability to the brain disease of 
addiction, even though there is not any evidence that addiction follows a 
strictly Mendelian pattern of inheritance in humans.

The challenge for the molecular genetics of addiction, like many other 
complex genetic disorders lacking simple patterns of Mendelian inheritance in 
humans, is addressing the complexity of polygenic disorders with substantial 
environmental influences.  Continued advances during the next 5-10 years will 
enhance the study of the molecular genetics of addiction vulnerability.

Research Scope and Goals

This PA encourages applications for research projects that identify 
chromosomal loci and variation in genes that are associated with increased 
vulnerability to addiction.  Genetic approaches may include but are not 
limited to linkage, linkage disequilibrium, and association studies.  Data 
may be collected from the general population, population isolates, and/or 
recent admixed populations.  Standard and novel methods of analysis for the 
identification of genetic variation conferring vulnerability to a complex 
genetics disorder such as drug addiction are highly encouraged.  
Investigators may include, as a component of their project, non-human models 
to study the genetics of addiction vulnerability.

Phenotype definition of both affected and unaffected individuals is a central 
issue in the analysis of complex traits such as addiction.  The use of 
phenotypes defined by quantity-frequency criteria and diagnostic criteria 
(such as the DSM-III-R or DSM-IV criteria) that have been shown to have 
significant heritability in twin and/or adoption studies is strongly 
encouraged.  For diagnostic purposes, there are numerous structured or semi-
structured assessment instruments with high diagnostic reliability, including 
the Structured Clinical Interview for DSM-III-R or IV (SCID), the Psychiatric 
Research Interview for Substance and Mental Disorders (PRISM), the Structure 
Clinical Assessment for Neuropsychiatry (SCAN), the Composite International 
Diagnostic Interview (CIDI), the CIDI-Substance Abuse Module (CIDI-SAM), the 
Diagnostic Interview Schedule (DIS), and the Alcohol Use Disorder and 
Associated Disabilities Interview Schedule (AUDADIS).  

However, alternative phenotype definition may better describe the genetic 
aspects of addiction.  Therefore, investigators may propose the use of other 
phenotype markers such as the presence or absence of biological markers or 
exhibition of unique individual traits, as well as combinations of these or 
co-morbid condition.  In addition, the use of advanced analytical methods 
such as principal-components analysis, discriminant analysis, or artificial 
neural networks may help define groups of phenotypes with a higher 
heritability for complex traits.

Identifying specific genes that mediate addiction or other complex, multi-
genic diseases is complicated by the fact that analytical methods developed 
for single-gene disorders do not necessarily incorporate the effects of gene 
interactions.  Investigators are encouraged to consider using innovative 
genetic models, pedigree structure, and methods of statistical analysis for 
the identification of genetic variations conferring vulnerability to a 
complex genetics disorder such as drug addiction.

Data from laboratory, field and clinical research is beginning to show gender 
differences in biological factors in drug abuse, the progression and 
initiation to drug use and abuse, the antecedents and consequences of drug 
use and abuse, and prevention and treatment. Examination of gender 
differences in the molecular genetics of addiction vulnerability is highly 

The NIDA Genetics Consortium (NGC)

The nucleus of the NIDA Genetics Consortium (NGC) are investigators who were 
awarded grants under the RFA, "Genetics of Drug Addiction Vulnerability" (DA-
99-003) as well as those who have modified their projects to conform to the 
guidelines listed in that RFA to use the resources provided by the NIDA 
Center for Genetics Studies.  The NIDA Center for Genetics Studies is funded 
by a contract awarded to Rutgers University with a subcontract to Washington 
University for the purpose of creating databases, cell lines, and DNA 
samples, and for wide distribution of the data and DNA to the scientific 
community.   After a proprietary period, the NIDA Center for Genetics Studies 
will, upon proper application and approval, distribute both the data and DNA 
samples to qualified researchers.   Members of the NGC meet two to three 
times a year to discuss issues related to the molecular genetics of addiction 

Investigators belonging to NGC have developed detailed plans for the 
dissemination and distribution of all clinical, diagnostic, and pedigree 
information, as well as the generation of cell lines and the distribution of 
DNA, 12-18 months after the funding period.  As part of the sharing plan, the 
investigators belonging to the NGC agree to send blood samples from study 
subjects and specific diagnostic and descriptive data to a repository (NIDA 
Center for Genetics Studies).  These specific diagnostic and descriptive data 
include 1) subject ID #, 2) family ID #, 3) site ID #, 4) parental ID #s, 5) 
sex, 6) death status, 7) ethnicity or geographic origin of ancestry, 8) age 
and/or year of birth, 9) twin status, 10) DSM-III-R diagnoses, 11)  DSM-IV 
diagnoses, 12) instrument used to establish diagnoses, 13) answers to all of 
the questions in the structured interview or, minimally, the answers to those 
questions from which the addiction diagnoses were established, 14) age of 
onset of drug dependence and quantity-frequency of peak lifetime use of all 
addictive substances, and 15) Proband.  Applicants responding to this 
announcement are strongly encouraged to join the NGC.  Applicants wishing to 
join the NGC are expected to follow the stipulations under special 
requirements in the RFA "Genetics of Drug Addiction Vulnerability" and to seek 
the advice of program staff.  By joining the NIDA Genetics Consortium the 
applicant will:  

o  Increase statistical power of the samples being collected,

o  Enhance quality control of the data collected,

o  Facilitate and enhance opportunities for collaboration,

o  Have access to a data management facility to create extensively documented 
files at no cost,

o  Have high quality cell lines produced upon receipt of blood samples, 

o  Have aliquots of high quality DNA extracted from the cell lines and 
returned at no cost,
o  Have an unlimited supply of DNA, and

o  Be able to devote more resources to data collection and data analysis.

Investigators with a currently funded NIH grant with specific aims related to 
the genetics of addiction who would like to join the NIDA Genetics Consortium 
should also contact the program official listed at the end of the 

Available Genotyping Resources

Investigators should note that an existing resource available to 
investigators for genotyping is the Center for Inherited Disease Research 
(CIDR), which is supported by a contract to Johns Hopkins University by eight 
NIH institutes including NIDA.  CIDR was established in 1996 to provide high-
throughput genotyping and statistical services for complex genetic diseases 
to the scientific community at large.  Introductory no cost access to CIDR 
resources is available to investigators who have been approved by the CIDR 
Access Committee (CAC) and who are supported by one of the eight supporting 
NIH institutes (including NIDA).  Thus, projects supported by this PA are 
eligible for no cost access to CIDR resources following CAC approval.  
Investigators should request access to CIDR resources, if needed, and obtain 
CIDR approval before the requested start date of the grant.  The deadlines 
for submission of applications requesting CIDR access are November 1, 
February 1, and June 1.  For more information about CIDR, see the CIDR Web 
site at or contact Dr. Jerry Roberts at
301-402-0838 or at

Alternatively, investigators may wish to use the Mammalian Genotyping Service
at the Marshfield Medical Research Foundation in Marshfield, Wisconsin.  
This facility is sponsored by the 
National Heart, Lung, and Blood Institute (NHLBI) at NIH and is provided 
at no cost to investigators whose projects are approved for genotyping by 
the Scientific Advisory Panel of the Mammalian Genotyping Service.  
For submission dates, investigators should contact the Mammalian Genotyping 
Service at (715) 387-9150.


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 
in the Federal Register)  
Accordingly, to address the interests of the research community and 
government in promoting the science of the genetic basis of drug addiction 
vulnerability, NIDA 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 


It is the policy of the NIH that women and members of minority groups and 
their subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale or justification is provided that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research.  This new policy results from the NIH Revitalization Act of 
1993 (Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research," which have been published in the Federal Register on March 28, 
1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, 
Volume 23, Number 11, March 18, 1994, and is available on the web at the 
following URL address


It is the policy of NIH 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 was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning these policies.


The National Advisory Council on Drug Abuse recognizes the importance of 
research involving the administration of drugs to human subjects and has 
developed guidelines relevant to such research.  Potential applicants are 
encouraged to obtain and review these recommendations of Council before 
submitting an application that will administer compounds to human subjects.  
The guidelines are available on NIDA’s Home Page at under 
Funding or may be obtained by calling (301) 443-2755.

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  Application kits are available at most 
institutional offices of sponsored research and may be obtained from the 
Division of Extramural Outreach and Information Resources, National 
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-
7910, telephone (301) 710-0267, E-mail:

Applicants planning to submit an investigator-initiated new (type 1), 
competing continuation (type 2), competing supplement, or any amended/revised 
version of the preceding grant application types requesting $500,000 or more 
in direct costs for any year are advised that he or she must contact the 
Institute or Center (IC) program staff before submitting the application, 
i.e., as plans for the study are being developed.  Furthermore, the 
application must obtain agreement from the IC staff that the IC will accept 
the application for consideration for award.  Finally, the applicant must 
identify, in a cover letter sent with the application, the staff member and 
the Institute or Center who agreed to accept assignment of the application.

This policy requires an applicant to obtain agreement for acceptance of both 
any such application and any such subsequent amendment.  Refer to NIH Guide 
for Grants and Contracts, March 20, 1998 at


The modular grant concept establishes specific modules in which direct costs 
may be requested, as well as a maximum level for requested budgets.  Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only 
when there is a possibility for an award.  It is anticipated that these 
changes will reduce the administrative burden for the applicants, reviewers, 
and Institute staff.  The research grant application form PHS 398 (rev. 4/98) 
is to be used in applying for these grants, with the modifications noted 


Modular Grant applications will request direct costs in $25,000 modules, up 
to a total direct cost request of $250,000 per year.  (Applications that 
request more than $250,000 direct costs in any year must follow the 
traditional PHS 398 application instructions.)  The total direct costs must 
be requested in accordance with the program guidelines and the modifications 
made to the standard PHS 398 application instructions described below:

PHS 398

FACE PAGE - Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular 
Total Direct plus Facilities and Administrative (F&A) costs] for the initial 
budget period. Items 8a and 8b should be completed indicating the Direct and 
Total Costs for the entire proposed period of support.

of the PHS 398.  It is not required and will not be accepted with the 

categorical budget table on Form Page 5 of the PHS 398.  It is not required 
and will not be accepted with the application.

NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative 
page (see for sample 
At the top of the page, enter the total Direct Costs requested for each year.  
This is not a Form page.

Under Personnel, list key project personnel, including their names, percent 
of effort, and role in the project.  No individual salary information should 
be provided.  However, the applicant should use the NIH appropriation 
language salary cap and the NIH policy for graduate student compensation in 
developing the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (Direct 
plus F&A) for each year, each rounded to the nearest $1,000.  List the 
individuals/organizations with whom consortium or contractual arrangements 
have been made, the percent effort of key personnel, and the role in the 
project.  Indicate whether the collaborating institution is foreign or 
domestic.  The total cost for a consortium/contractual arrangement is 
included in the overall requested Modular Direct Cost amount.  Include the 
letter of intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the 
number of modules requested.

BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by 
reviewers in the assessment of each individual"s qualifications for a 
specific role in the proposed project, as well as to evaluate the overall 
qualifications of the research team.  A biographical sketch is required for 
all key personnel, following the instructions below.  No more than three 
pages may be used for each person.  A sample biographical sketch may be 
viewed at:

- Complete the educational block at the top of the Form page,
- List position(s) and any honors,
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years, and
- List selected peer-reviewed publications, with full citations.

CHECKLIST - This page should be completed and submitted with the application.  
If the F&A rate agreement has been established, indicate the type of 
agreement and the date.  All appropriate exclusions must be applied in the 
calculation of the F&A costs for the initial budget period and all future 
budget years.

The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review. 

The title and number of the PA must be typed on line 2 of the face page of 
the application form and YES box must be marked.

Submit a signed, typewritten original of the application, including the 
Checklist, and five signed photocopies in one package to:

6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)


Applications will be assigned on the basis of established PHS referral 
guidelines.  Applications will be evaluated for scientific and technical 
merit by an appropriate scientific review group and convened in accordance 
with the standard NIH peer review procedures.  As part of the initial merit 
review, all applications will receive a written critique and undergo a 
process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and 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.  Each 
of these criteria will be addressed and considered in assigning the overall 
score, weighting them as appropriate for each application.  Note that 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.

(1) 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?

(2) 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?

(3) Innovation:  Does the project employ novel concepts, approaches or 
method? Are the aims original and innovative?  Does the project challenge 
existing paradigms or develop new methodologies or technologies?

(4) 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)? 
(5) 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 

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities, and their 
subgroups as appropriate for the scientific goals of the research.  Plans for 
the recruitment and retention of subjects will also be evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.


Awards will compete for available funds with all other recommended 
applications.  The following will be considered in making funding decisions:  
Quality of the proposed project as determined by peer review, availability of 
funds, and program priority.  


Inquiries are encouraged.  The opportunity to clarify any issues or questions 
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Jonathan D. Pollock, Ph.D.
Division of Basic Research
National Institute on Drug Abuse
6001 Executive Blvd., Room 4274, MSC 9555
Bethesda, MD 20892-9555
Telephone:  (301) 443-6300
FAX:  (301) 594-6043

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD  20892-9541
Telephone:  (301) 443-6710
FAX:  (301) 594-6847

Direct inquiries regarding review matters to:

Teresa Levitin, Ph.D.
Office of Extramural Affairs
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone: (301) 443-2755
FAX: (301) 443-0538


This program is described in the Catalog of Federal Domestic Assistance No. 
93.279.  Awards are made under authorization of sections 301 and 405 of the 
Public Health Service Act as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-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, and 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

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