The Application of
Genetic and Genomic
Research to Nursing Science
Yvette P. Conley, PhD
Associate Professor of Nursing and
Human Genetics
University of Pittsburgh
Discussion Today…

Some background
 Genetic/Genomic research approaches
and tips for integration into your research
 Resources of interest
 There is support
The field of genetics has
changed…
In the past … Our primary concern was
determining what gene and mutations
caused single gene disorders that had
predictable inheritance patterns (eg CF,
SCA, PKU)
The field of genetics has
changed…
Now… Much of our focus is on more
common, complex conditions, those of
great public health concern, variability in
patient experiences including symptoms,
and patient outcome related phenotypes
Now… Much more complex way of looking at
genetics/genomics, for example:
– Gene  Gene interactions
– Gene  Environment interactions
– Individualized therapies
Genetic…Genomic?
Genetics is used when referring to a single
gene
Genomics is used when referring to the
whole genome, multiple genes, gene-gene
interaction
Genomic Translational Research
Khoury MJ et al (2007) Genetics in Medicine, 9(10):665-674
Khoury MJ et al (2012) Am J Public Health 102(1):34-37
Frequently Utilized
Approaches to Genetic and
Genomic Research

Association
– Case/control
– Family
– Genome wide association studies (GWAS)
 Gene Expression
 Epigentics/Epigenomics
Candidate Gene Association
Studies

A candidate gene association study is used when
you have an educated guess about a genes
involvement in the condition you’re investigating

Can use unrelated individuals or families 
advantage is ability to use unrelated individuals
particularly if studying a complex or age-related
condition, as well as phenotypes within the
context of an external event – such as recovery
after injury, symptoms within the context of an
illness, etc.
Association studies

Usually uses a case/control design and the cases
are compared to the controls to determine if genetic
variability differs significantly between them,
potentially indicating that the gene that houses that
variability is involved with that condition
 Requires some knowledge of the biology of the
condition in order to select appropriate genes to
investigate – potential disadvantage  what if we
don’t know much…or think we know but are not on
right track
 Can take confounding data, such as environmental
exposures, into consideration
 Selection of appropriate control group very
important
Genome Wide Association Studies
A Genome Wide Association Study (GWAS) is
used when you want to investigate the entire
genome to determine what polymorphisms
are associated with the condition you’re
studying
One advantage is the biology of the condition
does not need to be well understood. You
investigate the entire genome and see where
the data takes you
One disadvantage is the large number of
subjects required
Genome Wide Association Studies

The usefulness of GWAS has sparked a call
for GWAS data to be placed into large
databanks for investigators to mine for
association with a variety of characteristics
(NIH data sharing plan)

Visit http://www.ncbi.nlm.nih.gov/WGA for
updates on what cohorts have agreed to
have their data made available
Genome Wide Association Studies

archive and distribute the results of studies
that have investigated the interaction of
genotype and phenotype
dbGaP: Framingham Heart Study
Study
Participants
Entire study
14276
Cancer
3373
Diabetes
6071
MMSE
6256
Menopause data
5360
CRP
8287
Inflammatory
Markers
>7000 for most
dbGaP: Framingham Heart Study
Study
Participants
Pulmonary
function test
9007
SF-36
2952
Hormone data
3925
Abdominal fat
study
3384
Brain MRI
2727
Cardiac CT
scans
3518
dbGaP: Framingham Heart Study
Study
Participants
Dementia
2715
Digital ECG
11828
Echocardiography
4079
Bone density
4728
Plasma Renin
3352
Osteoarthritis
study
1333
dbGaP: Other studies in db
Study
Collaborative study
of psoriasis
Multicenter ADHD
project
GWAS of
Schizophrenia
Major Depression
Diabetic
Nephropathy in
type I diabetes
Participants
2875
2835
5066
3741
1825
dbGaP: Other studies in db
Study
Participants
WGAS of Bipolar
Disorder
2160
Whole Genome
Association Study of
Visceral Adiposity in
the HABC Study
2802
LEAPS study*
1550
AREDS
Multiple releases 4757
* Linked Efforts to Accelerate Parkinson’s Solutions collaboration
dbGaP: Other studies in db
Study
Participants
NINDS Parkinsonism
study
1283
NINDS Parkinson’s
535
NINDS repository of
neurologically normal
control collection
2723
Dental Caries GWAS
5291
High Density SNP
Association Analysis
of Melanoma
3115
dbGaP: Other studies in db
Study
Participants
FUSION study*
1283
GENEVA Diabetes
Study (NHS/HPFS)
6033
Women's Health
Initiative SHARe
12,008
Preterm birth
1029
Health and Retirement
Study
12,507
* Finland-United States Investigation of NIDDM
Expression Analysis

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Expression analysis is used when you suspect
that variable amounts or variable forms
(alternative splicing/isoform) of a gene product is
playing a role in the condition you’re studying
remember genemRNAprotein
Gene expression can be assessed at the protein
or mRNA level
Potential disadvantages  usually need to
extract from tissue of interest and stability of
sample may be an issue
Frequently uses “microarray” technology to
assess all known genes simultaneously
If using relative gene expression changes then
how you’ll compare subjects/groups is important
Epigenetic/Epigenomic

Epigenetic/Epigenomic analysis is used when you
suspect that gene regulation may be implicated in a
condition of interest
– Candidate gene/gene region  epigenetic
– Multiple genes/whole genome  epigenomic
 involves looking at modifications that do not involve the
nucleotide bases of DNA but instead look at things like
chemical modifications (such as DNA methylation) or
packaging of the DNA
 Epigenetic/epigenomic modifications are dynamic and
responsive to environment (endogenous and
exogenous)
 Advantage  uses DNA as template and DNA is stable,
so may be more amenable approach for stored samples
 Disadvantage  tissue specificity
Strategies to incorporate
genomics into your research
trajectories




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Collect samples and bank them for future use
– Broadly written informed consent to cover future
investigations
Tap into existing samples/data to investigate your
research questions  be mindful of how samples
stored and how that may impact utility for a particular
approach
Collaborate – you may be interested in a phenotype
that someone with samples may not have considered
Visit and Exploit online resources as much as possible
The techniques to collect and analyze genetic/genomic
data advances rapidly – keep yourself informed
Funding is favorable, often viewed as innovative to add
a genetic/genomic component
NINR Strategic Plan
To advance the science of health, NINR will
invest in research to:

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
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Enhance health promotion and disease prevention
Improving Quality of Life by managing symptoms
of acute and chronic illness
Improve palliative and end-of-life care
Enhance innovation in science and practice
Develop the next generation of nurse scientists
www.ninr.nih.gov/AboutNINR
Enhance health promotion and
disease prevention

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Biology and Behavior are important factors
– Biology often impacts behavior and behavior often
impacts biology  incorporating both into research
trajectories focusing on health promotion and disease
prevention makes sense
“…evaluate health risks in diverse communities by
exploring the multiple factors that underlie susceptibility and
mediate risk for developing disease and illness …”
“…the development of innovative interventions tailored to
the individual will improve health behaviors, decrease the
incidence of acute and chronic illness, and advance health
outcomes while reducing health care costs…”
Improve Quality of Life by
Managing Symptoms of Acute
and Chronic Illness

Not all patients will experience symptoms or
experience them to the same extent  this variability
may at least in part be due to genetic variability, this
is also true of their caregivers
 Variability in response and adherence to
interventions (including behavioral) may at least in
part be due to genetic variability
 “NINR will invest in basic, clinical, and translational
research that: Improves knowledge of biological and
genomic mechanisms associated with symptoms and
symptom clusters”
 “NINR will invest in basic, clinical, and translational
research that: Studies the multiple factors that influence
the management of symptoms and applies this
knowledge to the design of personalized interventions”
Improve Palliative and End-ofLife Care

Adequate management of pain, fatigue
and depression require understanding
mechanisms and variability in response
 End-of-Life experiences of patients with
genetic conditions
 End-of-Life issues confronted by family
members of people with genetic
conditions  keeping in mind that genetic
conditions are different, family members
might face same disease or have been
spared
Enhance Innovation in Science
and Practice


“Rapid advances in technology and genomic
science, as well as significant changes in
demographics and health care policies and practice,
have placed pressing demands on nursing to find
fresh approaches and interventions that improve
health outcomes”
“The frontier of technology holds great promise for
advances in health care. For example, NINR will
continue to develop and refine the application of
genetic and genomic science to improve risk
assessment and identify potential interventions”
Develop the Next Generation of
Nurse Scientists

Summer Genetics Institute
– Summer 2013 will be 14th year of training
– over 240 alumni
– SGI “express”
 Individual Training Grants (mostly F31s)
with “genetic” as a key word: n=49
separate grants funded as of April 9, 2013
Funding for Genetics/Genomics
by the NINR

As of April 2013, the NINR has funded 111
extramural research grants (R’s, K’s, P’s)
that have a genetic or genomic theme to
the objectives of the projects based on
data obtained from NIH RePORTER
 Compared to May 2010, when the NINR
had funded 73 extramural grants that had
a genetic or genomic theme to their
objectives (38 in past 3 years)
Funding for Genetics/Genomics
by the NINR

Since 1/1/2000 the NINR has participated in
271 Request for Applications (RFA) or
Parent Announcements (PA) that have
genetics or genomics listed within the
purpose, objectives, or potential
approaches
 Since 1/1/2000 the NINR has been the
issuing organization for 89 Request for
Applications (RFA) or Parent
Announcements (PA) that have genetics or
genomics listed within the purpose,
objectives, or potential approaches
Funding for Genetics/Genomics
by the NINR
Exemplars of recent RFAs:
 2010: RFA-NR-10-004 (R01) and RFA-NR-10005 (R21) focused on “Epigenetic Factors
Associated with Symptoms and Complications
of Chronic Disorders”
 2011:RFA-NR-11-003 (R01) and RFA-NR-11-004
(R21) focused on “Personalized Genomics for
Symptom Management: Bridging the Gaps
from Genomic Discovery to Improved Health
Outcomes”
 2012: RFA-NR-12-002 (R01) and RFA-NR-12003 (R21) focused on “Application of Genomic
Advances to Wound Repair”
Funding for Genetics/Genomics
by the NINR
Exemplars of recent RFAs:
 RFA-NR-12-010 focuses on “Early Detection and
Prevention of Mild Cognitive Impairment
(R01)”…”Utilization of biomarker or genetic
information to examine similarities and
differences in MCI and its sequelae among those
diagnosed with LLI and appropriate controls”
 RFA-NR-12-006 (P30) and RFA-NR-12-009 (P20)
focuses on “Centers of Excellence in Symptom
Science”…”increase the quantity and quality of
research projects utilizing, genetics/genomics,
and biobehavioral methods”
Funding for Genetics/Genomics
by the NINR
Exemplar current RFA: due May 9, 2013
 RFA-NR-13-002 (R01) and RFA-NR-13-003 (R21)
focuses on “The Influence of the Microbiome on
Preterm Labor and Delivery”…”Genomic and
epigenomic variants that potentially interact or
associate with the microbiome in predisposing
women to preterm labor and delivery”
Useful Web Sites
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www.ncbi.nlm.nih.gov
– Has pull down menu that includes OMIM – Online
Mendelian Inheritance in Man, databases on
genomic variations (eg. SNP), dbGaP, and much
more
www.isong.org
– International Society of Nurses in Genetics
www.ons.org
– Oncology Nursing Society – has many tools
including online modules for nurses to learn more
about genetics
www.cdc.gov/genomics
– National Office of Public Health Genomics
– Can sign up for weekly updates via email
Useful Current/Upcoming
Literature
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Most recent issue (March 2013) of Journal of
Nursing Scholarship focused on
genetics/genomics particularly where we are with
evidence and translation to practice
2012 issue of Annual Review of Nursing Research
was focused on genetics/genomics
Throughout 2011 the Journal of Nursing
Scholarship had a series of articles that focused
on Genetics and Genomics in Nursing with
particular focus on educating nursing faculty,
nursing students, and patients
In Summary

Focus has shifted from rare single gene conditions to
common, complex disorders of major public health
concern and towards understanding patient
experiences/outcomes
 Mainstreaming of genetics/genomics
 Like many disciplines, translation of research is an
issue
 Nurses are well poised to address many of these
transitional arenas and many nurses ARE addressing
these arenas
 Incorporating genetics/genomics using suitable
approaches is appropriate for most programs of
research
 The next generation of Nurse Scientists will have
excellent representation of genetics/genomics
 The NINR supports genetic/genomic research/training