48x36 Poster Template

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The application of genome-wide association
studies of aging in a patient-driven clinical
trial outline Melanie Swan, Aaron Vollrath, Cindy
Chen Raymond McCauley, DIYgenomics, Palo Alto,
CA USA melanie_at_DIYgenomics.org 1.415.505.4426
www.DIYgenomics.org/aging_poster.ppt
5. Cancer
Background
1. Aging-specific GWAS
3. Catabolism (waste break-down) and other
The rapidly decreasing cost of whole genome
sequencing could soon make the Personal Genome a
reality for large numbers of individuals wanting
access to and interpretation of their genomic
information. Already the accessibility of this
information is providing an impetus for
patient-driven research. Though the advent of the
truly personal genome, whereby everyone has
access to their entire genomic data at an
affordable price is not yet here, a number of
options exist for individuals to obtain
genotyping data from consumer genomic services.
Costs range from 400-2,000 for genotyping
services to 20,000 for whole human genome
sequencing for consumers. As proof of principle
of a patient-driven clinical trial using personal
genomic data in the form of identified variants,
this study utilizes published data from
genome-wide association studies (GWAS) to link
genes and variants to a variety of biomarkers
associated with human aging. The study outline
takes into consideration GWAS results for
critical aspects of aging including the inability
to adequately regulate glucose levels, the
decline of the immune system, ineffective
catabolism, shortening of telomeres, and defects
in lipoprotein metabolism. Genotyping data for a
group of twenty citizen scientists is reviewed
and can be further integrated with phenotypic
measures of aging (including blood pressure,
cholesterol, BMI, VO2 max, erythrocyte
glycosylation, LDL particle size, telomere
length, and lymphocyte growth rate), and used as
the basis for proposed personalized
interventions. Citizen-science contributed
biobanks and databases are examined as a resource
for the immediate, cost-effective, and
large-scale application of research studies.
Figure 1
Figure 5
Figure 3
Discussion
These thousand variants associated with aging
and their corresponding phenotypic measures
provide the start of a comprehensive program for
personal aging measurement and intervention.
There are two kinds of intervention, traditional
solutions and novel solutions. Traditional
solutions consist of the usual condition
management through diet, exercise, vitamins, and
pharmaceuticals. Novel interventions consist of a
variety of emerging solutions, many of which are
speculative. Some of these include a crosslink
breakers supplement to improve systolic
hypertension (Zieman Journal of Hypertension
2007), brain fitness programs and mid-life
cholesterol management for Alzheimers disease,
TA-65 telomerase activation (TA Sciences) for
telomere length management, resistance weight
lifting for sarcopenia, interval training and
aerobic exercise for VO2 max improvement, and
blood-based assays for early detection and
response to rheumatoid arthritis (Swanson Nat Rev
Rheumatol 2009), macular degeneration
(MacuCLEAR), and kidney and liver disease.
2. Diabetes, lipids, and metabolic disease
Figure 2
4. Heart disease and blood operations
Methodology
The DIYgenomics study design methodology has
three steps identify strongly associated genomic
variants for specific conditions, find
corresponding phenotypic biomarkers, and
establish corresponding interventions to the
extent possible. Direct-to-consumer (DTC) genomic
services cover some aging conditions. These data
were included and supplemented with a more recent
and exhaustive self-curation of GWAS.
Self-curated GWAS references are cited DTC
references are available at DIYgenomics.org under
Health Risk. Approximately half of the SNPs
identified in DTC and DIYgenomics curation are
available for analysis in 23andme genotyping
files. The five categories of aging-related
GWAS are presented in Figures 1-5 aging-specific
GWAS, diabetes, lipids, and metabolic disease,
catabolism (waste break-down) and other, heart
disease and blood operations, and cancer. As
illustrated in Figure 1, the best-known processes
of aging are not yet extensively covered in human
GWAS, for example insulin/IGF-1 signaling
pathways, inflammation, mitochondrial
dysfunction, reactive oxygen species generation,
cell cycle, stem cell generation, and immune
response. Other areas such as diabetes and
adiposity (Figure 2) have broader coverage and
continue to be the focus of recent significant
findings of novel loci. New cancer studies
(Figure 5) have been more rare, and it is not
necessary to supplement DTC curation.
Figure 4
Conclusion
An urgent contemporary objective in public health
is to implement preventive medicine. Tools are
needed for personalized genome interpretation,
and the meaningful integration of multiple health
data streams various levels of genomic and
phenotypic data, and as they become available,
environmental, microbiome, and other data. The
large-scale open platforms of citizen science
biobanks could be ideal for crowdsourced
longitudinal data collection, targeted patient
recruitment, and the conduct of a new generation
of health research studies.
Acknowledgements
We would like to acknowledge review feedback from
Lorenzo Albanello, Mark Hamalainen, and Anne and
Gary Hudson. DIYgenomics is a non-profit
research organization coordinating patient-driven
clinical trials and providing personal genome
data applications for 20 health conditions and
250 pharmaceutical drugs at http//www.DIYgenomics
.org.