RELEASE DATE:  May 23, 2003


EXPIRATION DATE:  May 25, 2006, unless reissued.

National Institute on Aging (NIA)  



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


This program announcement (PA) solicits novel research integrating 
genetics, behavior and aging. Human and non-human studies are needed to 
advance our understanding of the genetic and environmental influences 
and processes affecting variability in behavior and its functional 
sequelae with age. This includes studies that help elucidate the 
relationships of levels and change in behavior to health, functional 
competence, and quality of life of older adults. This PA is framed 
around two broad categories of questions: (1) gene-to-behavior 
questions concerning the nature and role of genetic influences on 
behaviors at older ages, and how these genetic effects vary with age; 
and (2) questions about dynamic processes including gene-environment 
interactions, gene-environment covariation, age-related genetic 
effects, and how behaviors interact with and affect genetic expression.  
The behaviors that are eligible for study under this PA should be 
critical to quality of life among the aged, either as outcomes or as 
mediators of physical or cognitive health and function. Examples of 
relevant behavioral domains include, but are not limited to,  social 
behaviors, resilience, vitality, adaptivity, personality, vulnerability 
to stress, health behaviors, social cognition,  human and social 
capital accumulation, economic savings for retirement, risk-taking, 
happiness, coping, caregiving, cognitive abilities, cognitive 
flexibility, cognitive reserve, learning, and functional abilities.
This PA is intended to stimulate methodologically rigorous research 
integrating genetics, other biological sciences, and the behavioral and 
social sciences. To be considered responsive to this announcement, 
interdisciplinary perspectives must be unambiguous, the relationship 
between the behaviors or social processes under study and healthy aging 
should be articulated, and the proposed study should be embedded within 
a well articulated set of questions or hypotheses generated from social 
science and behavioral research. This announcement updates and replaces 
a previous Program Announcement, Behavior Genetics in Adulthood and Old 
Age (PAS-98-076, issued May 21, 1998).


Behavior and age-related changes in behavioral processes are integral to 
how well we age. Many behavioral phenotypes, such as resilience, 
cognitive and functional abilities, social connectedness, happiness, 
longevity and loneliness are intrinsic to maintaining health and quality 
of life. Behavior also plays a critical mediating role (e.g. smoking, 
alcohol use, exercise, risk taking behaviors, adherence, 
social engagement) in health and disease. Understanding the causes of 
variation in behavioral development, plasticity, stability, adaptation 
and change with age is essential to maintaining and enhancing quality of 
life throughout old age.  

Family and twin studies on aging have demonstrated the importance of 
genetic influences for variation in a large array of behavioral 
phenotypes related to personality, well-being, functional abilities, 
cognitive aging, longevity and health. More recent findings based on the 
longitudinal twin design indicate the importance of genetic influences 
on functional stability and the importance of environments for change. 
To move beyond these findings innovative studies are needed that 
investigate genetic effects within the context of the dynamic aging 
processes in which they are expressed. This will involve diverse 
approaches that: integrate molecular and quantitative methods, focus on 
behavioral systems for which known or candidate genes are identified, 
explore social processes that affect individual environments, include 
measures of biological intermediaries of the behaviors, and use non-
linear analytic approaches to study genes, social factors and 
environments in developmentally dynamic ways.

The underlying conceptual model is multifactorial, highlighting the 
combined action of multiple genetic and environmental influences where 
phenotypic variation arises as a function of genotypic and 
environmental differences between people within a particular 
population. Features of this model are an assumption that environmental 
influences, ranging from intracellular conditions to larger 
socio/cultural effects, and genetic influences operate through the same 
causal field of biological structures and processes. The intricacies of 
this causal field can lead to complex relationships between genetic 
factors, environmental influences, and phenotypic outcomes. These 
complexities include time-related changes in the relative influence of 
genetic and environmental factors, non-linear interactions among genes, 
interactions and correlations between genes and environments and 
environmentally induced gene expression.

The need to examine genetic and environmental influences and behaviors 
in the context of dynamism of interactive aging systems is increasingly 
apparent, and unprecedented opportunities to do so are now available. 
Dramatic advances have been made by molecular geneticists in the 
explication of hereditary phenomena, by quantitative geneticists in the 
assessment of aggregate effects of genes and environments, by 
behavioral and social scientists in identifying intermediary phenotypes 
(endophenotypes) and in defining and measuring complex behavioral 
domains, and by statisticians in the measurement of change. Progress in 
understanding gene-behavior relationships in aging will rely on 
integrating the theoretical models and methodologies of these research 
domains to provide powerful tools for combining reductionist approaches 
(that explore the nature of specific genetic and environmental 
influences) and integrationist approaches (that explore effects within 
the larger context of complex systems). Among many examples, improved 
strategies now exist to identify genes and map quantitative trait loci 
(QTL); to assess specific genetic and environmental sources of 
variation; to quantify these specific effects relative to background 
variation due to the aggregate influence of still-anonymous genes and 
environments; to conceptualize and examine non-linear and dynamic 
processes such as epistasis, gene-environment interaction, gene-
environment correlation, and behaviorally or environmentally induced 
genetic expression; to investigate how social worlds and behavioral 
factors modulate gene expression; to characterize population 
differences according to sequence (SNP) and haplotype diversity; to 
detail the structure of behavioral domains; to measure phenotypic 
change; and to assess age-related changes in influence of both specific 
and aggregate genetic and environmental domains.

A wide range of designs is relevant to the objectives of this program 
announcement, including augmented family studies with combinations of 
twins, parents, siblings, children and adoptees; sibling studies using 
highly selected samples for phenotypic indices of 
similarity/dissimilarity; extended pedigrees; special populations (i.e. 
inbred groups, cultural and genetic isolates); sub-populations such as 
the oldest-old; studies that utilize the extensive genome databases and 
genetic analyses resources that are becoming available; and animal 
model studies using cross-fostering, selective breeding, inbred 
strains, recombinant inbred strains or specific genotypic manipulations 
(e.g. transgenic, knock-outs, knock-ins).  Research is also encouraged 
that builds upon ongoing studies of aging cohorts whereby supplemental 
data collection would allow new hypotheses to be addressed at the 
intersection of genetics, behavioral and social science and research. 

Major methodological considerations should be well articulated, 
including the implications for aging of the behavioral phenotypes being 
studied, documentation of solid measurement characteristics, 
presentation of power analyses to reveal that sample sizes suffice for 
analyzing the genetic effects being studied, and clear descriptions of 
the analytical procedures to be employed must be provided.  The research 
team should be multidisciplinary and, at a minimum, reflect expertise in 
genetics (molecular and/or quantitative), and the social/behavioral 

Among the many research avenues pertinent to studying the behaviors of 
relevance to this PA are: 

o Studies that explore the genetics of behavioral interventions and 
address how genetic differences moderate responses among the elderly to 
health promoting behaviors (e.g. exercise, social connectedness, 
cognitive training). 

o Studies to elucidate behavior-gene (i.e. individuate loci and QTLs) 
relationships for behaviors affecting quality of life with aging.  
Novel, hypothesis-driven research is needed to:  1) investigate how 
genes or QTLs implicated in aging processes (e.g. oxidative stress) 
affect behavioral function and change, and 2) explore age effects in 
the genes or QTLs implicated in behavioral functioning (e.g. DRD4 and 
novelty-seeking, APOE and cognitive function). 

o Behavioral genetic designs (using human or animal models) that 
combine quantitative and molecular techniques to resolve variance and 
covariance structures more finely than has previously been accomplished 
by quantifying the influences of specific genes, QTLs and specific 
measured environments. 

o Behavioral genetic studies (using human or animal models) that 
investigate genetic variation and QTLs affecting rates and shapes of 
change in behavioral functioning. 

o Studies of specific environmental influences in genetically 
informative research on aging. Despite the importance of dynamic 
processes involving gene-environment interaction and covariation, 
measured environments are rarely included in human studies. Research is 
needed that incorporates critical features of diverse environments 
(i.e. social, economic, physical and cultural environments) into 
behavioral genetic studies of aging for the purpose of analyzing gene-
environment dynamics. 

o Studies (using human or animal models) to investigate gene by 
environment interaction. Examples include research exploring whether 
and how social environments or enriched experiences (quality of 
education, etc.) mediate progression to disease among those with 
genetic predispositions to disease; studies investigating the effects 
of socially or experientially enriched or restricted environments on 
genetic expression; research testing whether protective health effects 
conferred by education prevail in the presence of genetic risk, and 
genetic research that builds upon and bridges findings from established 
fields of environmental inquiry (e.g. health disparities) to explore 
gene by environment interactions. 

o Studies elucidating the genetic regulation of neural mechanisms, and 
their modulation by environmental circumstances, that impact upon 
cognitive function, cognitive reserve and flexibility, learning, and 

o Studies to investigate gene by environmental covariation. Individuals 
shape and select their environments throughout development, and these 
processes are affected by many factors including age, and aging 
transitions such as retirement, chronic care giving, bereavement, 
isolation and functional loss. Research is needed that develops 
analytical models by which to study gene-environment covariation in the 
context of these age-related changes in abilities to define and select 
one's environment. 


This PA will use the NIH R01 award mechanism.  As an applicant, you 
will be solely responsible for planning, directing, and executing the 
proposed project. 

This PA uses just-in-time concepts.  It also uses the modular as well 
as the non-modular budgeting formats (see  
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.

The NIA intends to commit at least $2 million for an initial round of 
funding of applications of high scientific merit in FY 2004. An 
applicant may request a project period of up to 5 years. Because the 
nature and scope of the proposed research will vary from application to 
application, it is anticipated that the size and duration of each award 
will also vary. Although the financial plans of the NIA provides 
support for this program, awards pursuant to this PA are contingent 
upon the availability of funds and the receipt of a sufficient number 
of meritorious applications. 


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


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.


An overarching goal of this PA is to encourage innovative research 
integrating knowledge and methodologies from genetics, gerontology, and 
the behavioral and social sciences. Applications should articulate the 
interdisciplinary dimensions and components of the proposed research, 
and explain how the collective expertise of the research team meets 
these interdisciplinary requirements with regards to the specific aims 
to be investigated. 

The sharing of unique resources such as phenotypic data, DNA, and 
genome scans in a timely manner contributes greatly to progress in 
understanding the genetics of complex phenotypes. The NIH encourages 
data sharing (
03-032.html) and requires all applications from October 1, 2003 that 
request $500,000 or more in direct costs in any single year to address 
data sharing. For this program announcement, investigators are 
encouraged to submit a data-sharing plan regardless of the size of the 
requested budget. The NIH data sharing and implementation guidelines 
policies can be found at
data_sharing_guidance.htm. NIH staff will evaluate the adequacy of 
the proposed data sharing and access plan, and consider it in making award 
decisions. Staff will also consider waivers as appropriate to the conditions 
of data collection. Also, except under circumstances where the data are 
likely to be of unique value and importance to other investigators, staff 
will accept requested costs under $500,000 a year as sufficient reason for 
a waiver. The sharing plan approved by NIH staff, after negotiation with 
the applicant when necessary, will become part of the terms and 
conditions of the award. NIH staff will also evaluate compliance with 
the sharing plan and scientific progress in the non-competing 
continuation of the grant award application.


We encourage your inquiries concerning this PA and welcome the 
opportunity to answer questions from potential applicants.  Inquiries 
may fall into two areas:  scientific/research, and financial or grants 
management issues:

o Direct your questions about scientific/research issues with primary 
emphasis on behavioral and social research on aging to: 

Angie Chon-Lee, MPH
Behavioral and Social Research Program 
National Institute on Aging 
Gateway Building, Room 533
Bethesda, MD  20892-9205
Telephone:  (301) 594 5943 
FAX:  (301) 402-0051

o Direct your questions about scientific/research issues related to the 
nervous system as well as mechanisms underlying cognitive functioning to:

Marilyn M. Miller, Ph.D.
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
Gateway Building, Suite 350
7201 Wisconsin Avenue
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494

o Direct your questions about financial or grants management matters to:

Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
Gateway Building, Room 2N212
Bethesda, MD  20892
Telephone:  (301) 496-1472
FAX:  (301) 402-3672


Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email:

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

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 includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at

YEAR: Applications requesting $500,000 or more in direct costs for any 
year must include a cover letter identifying the NIH staff member 
within one of the NIH institutes or centers who has agreed to accept 
assignment of the application.   

Applicants requesting more than $500,000 must carry out the following 

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 

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 received by or mailed on 
or before the receipt dates described at  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.


Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review 
group convened in accordance with the standard NIH peer review 
procedures ( 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 the appropriate national advisory 
council or board.


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 your 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 your application's overall score, weighting them 
as appropriate for each application.  Your 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, 
you 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 your study address an important problem? If the 
aims of your application are achieved, how do they advance scientific 
knowledge?  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?  Do you acknowledge potential problem areas and 
consider alternative tactics?

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

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

(5) ENVIRONMENT:  Does the scientific environment in which your 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?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

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).
of plans to include subjects from both 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).


BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.


Applications submitted in response to a 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 (including adequacy of plans to share data).


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 AMENDMENT 
"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 (
guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated 
Guidelines are available at
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 

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 

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

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

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.

The Department of Health and Human Services (DHHS) issued final 
modification to the "Standards for Privacy of Individually Identifiable 
Health Information", the "Privacy Rule," on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as "covered entities") must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
( provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on "Am 
I a covered entity?"  Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at

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 

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

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.866, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.  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 described at and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and to 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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