GENETIC STUDIES IN ALCOHOL RESEARCH

NIH GUIDE, Volume 22, Number 19, May 21, 1993



PA AVAILABLE:  PA-93-086



P.T. 34



Keywords:

  Alcohol/Alcoholism 

  Genetics 

  Biology, Molecular 



National Institute on Alcohol Abuse and Alcoholism



THE PROGRAM ANNOUNCEMENT (PA) ANNOUNCED IN THIS NOTICE CONTAINS

ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION.

POTENTIAL APPLICANTS MAY OBTAIN THE PA FROM THE CONTACT NAMED IN

INQUIRIES, BELOW.



PURPOSE



The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is

seeking research grant applications to study the genetic basis of

alcoholism and the medical consequences of excessive alcohol

consumption.  Alcoholism has been recognized for over a century as a

familial condition, and considerable evidence has accumulated in

support of important roles for both genes and environment in its

etiology.  The specific genetic factors underlying susceptibility to

alcoholism and its complications remain, however, largely unknown.

The NIAAA encourages the submission of grant applications proposing

use of current genetic methods to elucidate these factors, either in

humans or in animal models.  Characterization and isolation of genes

underlying susceptibility to alcoholism and its complications will

allow early identification of individuals at risk, will help improve

the design of studies of environmental factors conducive to

alcoholism and its complications, and may ultimately improve

pharmacotherapy for alcoholism and its complications by facilitating

the design of drugs that interact with the products of these genes.

Insofar as a capacity to prevent and remediate excessive consumption

of alcohol will naturally lead to a reduction in the occurrence of

its attendant medical complications, the NIAAA's primary interest is

in factors predisposing to excessive alcohol consumption.



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This program

announcement, Genetic Studies in Alcohol Research, is related to the

priority area of alcohol abuse reduction.  Potential applicants may

obtain a copy of Healthy People 2000 (Full Report:  Stock No.

017-001-00474-0, or Summary Report:  Stock No. 017-001-00473-1)

through the Superintendent of Documents, Government Printing Office,

Washington, DC 20402-9325 (telephone:  202-783-3238).



ELIGIBILITY



Applications may be submitted by domestic and foreign, public and

private, non-profit and for-profit organizations, such as

universities, colleges, hospitals, research institutes and

organizations, units of State and local governments, and eligible

agencies of the Federal government.  Women and minority investigators

are encouraged to apply.  Foreign applicants are not eligible for

First Independent Research Support and Transition (FIRST) awards

(R29).



MECHANISMS OF SUPPORT



Research support may be obtained through applications for a research

project grant (R01), small grant (R03), exploratory/developmental

grant (R21), or FIRST (R29) award.



Potential applicants for small grants (R03),

exploratory/developmental grants (R21), and FIRST (R29) awards may

obtain copies of the specific announcements for these programs from

the National Clearinghouse for Alcohol and Drug Information, P.O. Box

2345, Rockville, MD 20847-2345, telephone  301-468-2600 or

1-800-729-6686.  Although program project grants (P01) will be

considered for funding, due to budget constraints and NIAAA

requirements for program balance, applications are not generally

encouraged.  Applications for program projects may not be submitted

without presubmission clearance by NIAAA program staff.



FUNDS AVAILABLE



Although the NIAAA desires to stimulate research in this area, no

specific funds are being allocated for this program at this time.

The amount of funding available will depend on appropriated funds,

quality of research proposals, and program priorities at the time of

the award.  In FY 1992, six new and competing renewal grants related

to this program area were funded for approximately $1,213,000 in

total costs.



RESEARCH OBJECTIVES



The following list of topics is intended only to illustrate NIAAA

interests; topics not mentioned are not necessarily excluded from

consideration.



Twin and adoption studies as a means of defining more precisely which

aspects of the alcoholic phenotype are most strongly heritable.



Studies to find genetic markers that cosegregate with alcoholism and

its complications in pedigrees of alcoholic families, or that are

associated with these disorders in populations.  Case-controlled

allelic association studies are considered responsive to this program

announcement only when the investigator expresses a clear intent to

confirm any positive findings with evidence from other sorts of

studies (e.g., linkage analysis).  NIAAA would particularly like to

encourage investigators wishing to test newly developed methods of

pedigree analysis that have the potential to detect linkage in the

presence of genetic heterogeneity.



Studies to elucidate specific genetic factors predisposing to medical

complications of alcoholism (e.g., liver cirrhosis, cardiomyopathy,

pancreatitis, Wernicke-Korsakoff's Syndrome), and fetal alcohol

syndrome (FAS).



QTL mapping of genes influencing ethanol-related behaviors (e.g.,

ethanol sensitivity, preference, tolerance, locomotor stimulation,

and withdrawal) in rodents.



Targeted disruption of mouse genes encoding products known to play a

role in the ontogeny and function of the nervous and endocrine

systems and that might serve as possible targets for the actions of

ethanol.



Genetic analyses of less well-studied aspects of ethanol related

animal behavior (e.g., consumption of ethanol after stress, ethanol

effects on aggression and anxiety, ability of ethanol to serve as a

behavioral reinforcer, animal behaviors thought to model aspects of

human emotionality and personality) that might be informative about

human ethanol related behavior.



Genetic analysis (especially by mutagenesis screens) of

ethanol-related behavior, as well as effects on CNS function and

development in the fruit fly Drosophila melanogaster and the soil

nematode Caenorhabditis elegans.



Tests of the effects of ethanol on the expression of genes believed

to play a role in specification of the embryonic body plan,

especially those involved in development of the CNS.  Tests of the

roles of such genes in ethanol-induced teratogenesis by targeted

disruption in mice.  Both types of proposal will be considered

responsive to this program announcement only if they articulate

explicit mechanistic hypotheses about how changes in the function of

the genes proposed for study could lead to observed patterns of

ethanol-induced teratology.



Mapping (either by single-gene or QTL approaches) genes responsible

for interstrain differences in susceptibility to ethanol-induced

teratogenesis.



Attempts to induce teratogenesis by ethanol treatment in the zebra

fish Brachydanio rerio, and, if these attempts are successful,

intensive genetic analysis of this process.



SPECIAL REQUIREMENTS



In accordance with the PHS policy relating to distribution of unique

research resources produced with PHS funding (NIH Guide for Grants

and Contracts, Vol. 21, No. 33, pgs 4-5, September 11, 1992),

investigators proposing the development of certain specialized

genetic lines of animals (see RESEARCH OBJECTIVES, Animal Genetics,

QTL Mapping, above) will be required to submit an explicit plan for

making them available to other researchers desiring to use them

before an award will be made.



STUDY POPULATIONS



SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH

POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL

RESEARCH STUDY POPULATIONS



For projects involving clinical research, NIH requires applicants to

give special attention to the inclusion of women and minorities in

study populations.  If women or minorities are not included in the

study populations for clinical studies, a specific justification for

this exclusion must be provided.  NIH funding components will not

award grants that do not comply with these policies.



APPLICATION PROCEDURES



Applicants are to use the grant application form PHS 398 (rev. 9/91).

Applications will be accepted at the standard deadlines as indicated

in the application kit.  Application kits containing the necessary

forms and instructions (PHS 398) may be obtained from institutional

offices of sponsored research at most universities, colleges, medical

schools, and other major research facilities, and from the Office of

Grants Inquiries, Division of Research Grants, National Institutes of

Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone

301-710-0267.  Applicants for FIRST Awards (R29) must include three

letters of reference.  Non-conforming applications will be returned

without being reviewed.



Applicants from institutions that have a General Clinical Research

Center (GCRC) funded by the NIH National Center for Research

Resources may wish to identify the Center as a resource for

conducting the proposed research.  If so, a letter of agreement from

either the GCRC program director or Principal Investigator should be

included in the application material.



The signed original and five permanent, legible copies of the

completed application must be sent to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW CONSIDERATIONS



Applications received under this announcement will be assigned to an

Initial Review Group (IRG) in accordance with established PHS

Referral Guidelines.  The IRG, consisting primarily of non-Federal

scientific and technical experts, will review the applications for

scientific and technical merit.  Applications will receive a

second-level review by an appropriate National Advisory Council,

whose review may be based on policy as well as considerations of

scientific merit.  Small Grants (R03s) do not require a second level

review.



REVIEW CRITERIA



Research grant applications will be reviewed based on standard

criteria for scientific and technical merit.  The review criteria for

Small Grants (R03), Exploratory/Developmental Grants (R21), FIRST

Awards (R29), and Program Projects (P01) are contained in their

respective program announcements.



AWARD CRITERIA



Applications recommended for approval will be considered for funding

on the basis of the overall scientific and technical merit of the

proposal as determined by peer review, programmatic needs and

balance, and the availability of funds.



INQUIRIES



Potential applicants are encouraged to seek preapplication

consultation and may contact the individuals listed below for

consultation in preparing an application under this announcement.



Direct inquiries regarding genetic studies and requests for the PA

to:



Robert W. Karp, Ph.D.

Genetics Program

National Institute on Alcohol Abuse and Alcoholism

5600 Fishers Lane, Room 16C-05

Rockville, MD  20857

Telephone:  (301) 443-4223

FAX:  (301) 227-8673



Inquiries related to fiscal matters may be directed to:



Joseph Weeda

Grants Management Branch

National Institute on Alcohol Abuse and Alcoholism

5600 Fishers Lane, Room 16-86

Rockville, MD  20857

Telephone:  (301) 443-4703

FAX:  (301) 443-3891



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic

Assistance, No. 93.273.  Awards are made under the authorization of

the Public Health Service Act, Sections 301 and 464H, and

administered under the PHS policies and Federal Regulations at Title

42 CFR Part 52, "Grants for Research Projects," and Title 45 CFR

Parts 74 and 92, "Administration of Grants and 45 CFR Part 46,

"Protections of Human Subjects."  This program is not subject to the

intergovernmental review requirements of Executive Order 12372 or

Health Systems Agency review.



.

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