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BEHAVIOR GENETICS IN ADULTHOOD AND OLD AGE
Release Date: May 21, 1998
PA NUMBER: PA-98-076
P.T.
National Institute on Aging
National Institute of Mental Health
PURPOSE
The National Institute on Aging (NIA) and the National Institute of Mental
Health (NIMH) invite qualified researchers to submit research grant
applications on behavior genetics in adulthood and old age. The goal of
this program announcement (PA) is to further scientific knowledge about
the relative contributions of hereditary and environmental factors in the
health, well-being, and quality of life of adults (age 21 and over) and
older persons. This program announcement encourages research that will
address one or more of the following: a) behavior genetics and cognitive
functioning/intellectual ability, and b) behavior genetics and
personality.
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 PA is related
to age-related objectives, genetics and medicine, and mental health and
mental disorders. 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
202-512-1800).
ELIGIBILITY REQUIREMENTS
Applications may be submitted by foreign and domestic 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. Foreign organizations are
not eligible to submit program project (P01) applications. Racial/ethnic
minority individuals, women, and persons with disabilities are encouraged
to apply as principal investigators.
MECHANISM OF SUPPORT
The mechanisms of support will be the investigator-initiated research
project grant (R01) and program project grant (P01).
FISCAL YEAR
In fiscal years 1999 and 2000, a total of $1,000,000 will be available to
fund research grants, contingent on high scientific merit and program
priority.
RESEARCH OBJECTIVES
Behavioral genetics involves the identification and characterization of
both genetic and environmental sources of individual variation in
behavior. The nature vs. nurture debate has slowly given rise to the
current perspective of joint influence of genes and environment on
behavioral phenotypes. The two standard approaches for examining the
genetic basis of complex traits have been the monogenic and quantitative
genetic approaches. Single gene approaches have been particularly helpful
in classifying behavioral phenotypes with a dichotomous outcome. On the
other hand, the study of continuously distributed behavioral phenotypes
are not effectively addressed by these methods. Similarly, quantitative
approaches cannot provide a complete answer. In studies of this type, the
combinatory effects of multiple genes are elucidated, but the specific
genes involved are not isolated and identified. The advent of quantitative
trait loci (QTL) methods has allowed us to advance the notion that genetic
influence on complex behaviors and disorders is largely due to multiple
genes, and that these genes can have effects of varying sizes which
contribute cumulatively and interchangeably to behavior. Localization of
chromosomal regions that have influence on complex behaviors, identifying
the genes and gene products, and studying these genes and gene
constellations in humans and animal models will add further to our
knowledge of the relative contributions of genes and environment to
complex behaviors.
The elderly, an age group defined by its variability in behavioral traits
rather than its homogeneity, represent a frontier to be explored in
behavioral genetic studies. Despite the fact that the relative
contribution of genetics and environment to functioning, health, and
longevity is one of the key questions in gerontology, we know little about
the role of genetic and environmental factors in cognition and personality
traits in middle-aged and older adults. For example, a long-held
assumption from the field of gerontology was that genetic influence on
behavior decreased as people accumulated experience and expertise.
However, recent research conducted on adults indicates that the relative
magnitude of genetic influence on cognitive function remains substantial
throughout the life span. Besides providing elemental contributions to
the field of gerontological science, studies such as the ones encouraged
in this Program Announcement will help lay the foundation for rational
recommendations to extend health and vitality in the elderly.
Studies are encouraged that include: 1) multiple types of subject groups,
including sibling pairs, adoptees, and subjects sampled from the general
population; 2) unlike-sex dizygotic (USDZ) twins, which are the best
matched samples of humans for gender comparisons (USDZ samples allow a
greater understanding of gender-based individual differences in aging); 3)
USDZ samples with siblings to conduct QTL analyses; 4) samples from
special populations, such as centenarians and subpopulations; and 5)
same-sex twins reared together and apart. Also encouraged are studies
that include the use of transgenic animal models, gene mapping, gene
knock-outs/knock-ins, or conditional gene expression to identify and
characterize genes affecting behavior and to determine whether their
effects are modulated with age. These approaches promise new insights
into individual differences in behavioral stability and change with age.
Topical areas include, but are not limited to:
A. GENETICS AND COGNITIVE ABILITY
Cognitive functioning and integrity are particularly crucial aspects of
quality of life for older persons. Projects on the heritability of
cognitive abilities and how genetic effects of cognition are mediated, as
well as on the environmental sources of variation in cognitive abilities
are encouraged. Projects incorporating gene mapping, identification,
characterization, and the expression of relevant genes in late life would
be particularly useful. Cognitive domains that require further study
include, but are not limited to: general intellectual ability, memory,
learning, information processing speed, attention, and temporal
organization. Where practical, adjunct neuroimaging studies are
encouraged as one means of exploring biological markers of genetic
influence.
B. GENETICS AND PERSONALITY
Although issues of genetic and environmental components of variance in
personality traditionally have been important in behavioral genetics
research, little attention has been given to this dimension of behavior in
the elderly. For example, it is not known whether the relative
contributions of genetics and environment to personality change as people
age. As with cognition, are some types of traits more likely to change
than others? Research is needed in several domains in behavior genetics
and personality including, but not limited to: emotionality, sense of
control, neuroticism, extroversion, openness, agreeableness, and
conscientiousness. Gene mapping, identification, and characterization, as
well as the examination of the effects of aging on the expression of
relevant genes in late life would be particularly helpful in studies of
personality. Additionally, research is needed to understand the
correlation between personality and health outcomes in later life. Does
one cause the other, or are there common factors contributing to both
personality and health? If so, are any of these common factors genetic?
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
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 and justification is provided 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 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,
March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and
Contracts, Volume 23, Number 11, March 18, 1994.
Investigators may obtain copies of the policy from the program staff
listed under INQUIRIES. Program staff may also provide additional
relevant information concerning the policy.
NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN
RESEARCH INVOLVING HUMAN SUBJECTS
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 address:
http://www.nih.gov/grants/guide/notice-files/not98-024.html
<http://www.nih.gov/grants/guide/notice-files/not98-024.html>
NOTE: Applications received in response to this program announcement are
expected to focus on scientific issues related to aging and to
aging-related aspects of disease. In describing the plan to recruit human
subjects, investigators may cite a focus on aging or on aging-related
aspects of disease as the justification for why children will be excluded.
In this regard, applicants may use Justification 1, the research topic to
be studied is irrelevant to children, from the policy announcement.
APPLICATION PROCEDURES
Applications are to be submitted on the grant application form PHS 398
(rev. 5/95) and will be accepted at the standard application deadlines as
indicated in the application kit. Applications 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 301-435- 0714, email: Grantsinfo@nih.gov
<mailto:Grantsinfo@nih.gov>
The title and number of the program announcement must be typed in line 2
on the face page of the application. The completed original application
and five legible copies must delivered to:
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, SUITE 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
REVIEW CONSIDERATIONS
Applications will be assigned on the basis of established Public Health
Service referral guidelines. Applications will be reviewed for scientific
and technical merit by appropriate review committees of NIH, 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 applications under review,
will be discussed, assigned a priority score, and receive a second level
review by the 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 review, comments on the following aspects of the
application will be made in order to judge the likelihood that the
proposed research will have a substantial impact on the pursuit of these
goals. Each of the following criteria will be addressed and considered by
the reviewers in assigning the overall score weighting them as appropriate
for each application.
o 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?
o 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?
o 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?
o 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)?
o 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?
The initial review group will also examine: the appropriateness of
proposed project budget and duration; the adequacy of plans to include
both genders, children, and minorities and their subgroups as appropriate
for the scientific goals of the research and plans for the recruitment and
retention of subjects; the provisions for the protection of human and
animal subjects; and the safety of the research environment.
AWARD CRITERIA
Applications will compete for available funds with all other approved
applications assigned. 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
Inquiries are encouraged. The opportunity to clarify any issues or
questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Jared B. Jobe, Ph.D.
Behavioral and Social Research
National Institute on Aging
7201 Wisconsin Avenue, Suite 533, MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-3137
FAX: (301) 402-0051
Email: Jared_Jobe@nih.gov <mailto:Jared_Jobe@nih.gov>
Molly V. Wagster, Ph.D.
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3C307, MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Email: Molly_Wagster@nih.gov <mailto:Molly_Wagster@nih.gov>
Huber R. Warner, Ph.D.
Biology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C231, MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-6402
FAX: (301) 402-0010
Email: Huber_Warner@nih.gov <mailto:Huber_Warner@nih.gov>
Mary E. Farmer, M.D., M.P.H.
Genetic Basis of Behavior Program
National Institute of Mental Health
5600 Fishers Lane, Room 10C-28
Rockville, MD 20857
Telephone: (301) 443-1411
FAX: (301) 443-9890
Email: Mary_Farmer@nih.gov <mailto:Mary_Farmer@nih.gov>
Direct inquiries regarding fiscal matters to:
Mr. Joseph Ellis
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-1472
FAX: (301) 402-3672
Email: Joseph_Ellis@nih.gov <mailto:Joseph_Ellis@nih.gov>
Ms. Diana Trunnell
Grants Management Branch
National Institute of Mental Health
5600 Fishers Lane, Room 7C-08
Rockville, MD 20857
Telephone: (301) 443-2805
FAX: (301) 443-6885
Email: Mary_Farmer@nih.gov <mailto:Mary_Farmer@nih.gov>
Relevant Literature
Cho, Y. H., Giese, K.P., Tanila, H., Silva, A., & Eichenbaum, H. (1998).
Abnormal hippocampal spatial representations in alpha-CaMKII and CREB
mice. Science, 269, 267-269.
Giese, K. P., Federov, N. B., Filipkowski, R. K., & Silva, A. J. (1998).
Autophosphorylation at threonine 286 of the
alpha-calcium-calmodulin-kinase II in LTP and learning. Science, 269,
270-273.
Mayford, M., Bach, M. E., Huang, Y.-Y., Wang, L., Hawkins, R. D., &
Kandel, E. R. (1996). Control of memory formation through regulated
expression of a CaMKII transgene. Science, 274, 1678-1683.
McArdle, J. J., & Prescott, C. A. (1996). Contemporary models for the
biometric genetic analysis of intellectual abilities. In D. P. Flanagan,
J. L. Genshaft, & P. L. Harrison, Contemporary intellectual assessment:
Theories, tests, and issues (pp. 403-436). New York: Guilford.
McClearn, G. E., Johansson, B., Berg, S., Pedersen, N. L., Ahern, F.,
Petrill, S. A., & Plomin, R. (1997). Substantial genetic influence on
cognitive abilities in twins 80 or more years old. Science, 276,
1560-1563.
Pedersen, N. L. (1993). Genetic and environmental continuity and change
in personality. In T. Bouchard & P. Propping (Eds.), Twins as a tool of
behavioral genetics (pp. 147-162). New York: Wiley.
Plomin, R. Pedersen, N. L., Lichtenstein, P., & McClearn, G. E. (1994).
Variability and stability in cognitive abilities are largely genetic later
in life. Behavior Genetics, 24, 207-215.
Tonegawa, S., Tsien, J. Z., McHugh, T. J., Huerta, P., & Blum, K. I.
(1996). Hippocampal CA1-region-restricted knockout of NMDAR1 gene disrupts
synaptic plasticity, place fields, and spatial learning. Cold Spring
Harbor Symposia on Quantitative Biology, 61, 225-38.
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
No. 93.866, Aging Research, and No. 93.242, Mental Health Research.
Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42
USC 241 and 285) and administered under PHS grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74. 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, 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.