Genomic self-hacking: citizen science and the realization of personalized medicine
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Genomic self-hacking: citizen science and the realization of
personalized medicine
Melanie SwanGenome Geek 650-681-9482
@DIYgenomics www.DIYgenomics.org
Quantified Self Meetup Group
NASA AMES - July 19, 2011
Slides: http://slideshare.net/LaBlogga
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2July 19, 2011DIYgenomics.org
Future health: layers of preventive medicine
Individual
2. Preventive CareHealth Social NetworksCitizen Science Studies
Health Advisors
3. Traditional health care system and physicians
1. Automated digital health monitoring
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3July 19, 2011DIYgenomics.org
New concept of health self-management
Source: Extended from Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525, Figure 1.
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4July 19, 2011DIYgenomics.org
Genome hacking philosophy
Goal: preventive medicine Realize preventive medicine by establishing baseline markers
of wellness and pre-clinical interventions
Generalized hypothesis One or more polymorphisms may result in out-of-bounds
baseline levels of phenotypic markers. These levels may be improved through personalized intervention.
Source: http://diygenomics.pbworks.com/MTHFR
Genotype Phenotype Intervention Outcome+ + =
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5July 19, 2011DIYgenomics.org
DTC genomics – interpretation variance
Private data upload: Marat Nepomnyashy; https://addons.mozilla.org/en-US/firefox/addon/156946
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6July 19, 2011DIYgenomics.org
Open-source mobile apps (5,000+ downloads)
Health condition, drug response, athletic performance
23andMe data upload
Android
iPhone
Android development: Michael Kolb, Lawrence S. Wong, Laura Klemme, Melanie SwaniPhone development: Ted Odet, Greg Smith, Laura Klemme, Melanie Swan
“genomics”
“genomics”
T T T
T T T
T C C
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7July 19, 2011DIYgenomics.org
Vitamin B deficiency / MTHFR mutation
Do common mutations in the MTHFR gene prevent vitamin B from working correctly?
Test whether 2 variations in the MTHFR gene keep vitamin B9 (folic acid) from being metabolized into its active form (folate) rs1801133/C677T rs1801131/A1298C
Without this form of vitamin B, homocysteine may accumulate (risk of cardiovascular disease, etc.)
50% or more of the population may have some form of MTHFR polymorphism
Source: http://diygenomics.pbworks.com/MTHFR
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8July 19, 2011DIYgenomics.org
Homocysteine metabolism pathway
Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med. 2010 Dec 23; 2:e20.
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9July 19, 2011DIYgenomics.org
Vitamin B / MTHFR study protocol
1. Genotype
MTHFR gene SNPs:
rs1801133 (A/G)
rs1801131 (A/G)
2. Phenotype
Blood tests:
B-12 and
Homocysteine
3. Intervention
(2 week periods)
1. B-complex
2. L-methylfolate
3. B-complex + L-methylfolate
Investigate genotype-phenotype linkage and apply interventions to improve phenotypic outcomes
Protocol confirmed with two separate experts in the field
Source: http://diygenomics.pbworks.com/MTHFR
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10July 19, 2011DIYgenomics.org
Vitamin B / MTHFR pilot study results
Drug store vitamin (Centrum) reduced homocysteine levels for 6/7 participants
Blood Test #
2. Homocysteine levels
DIYgenomics MTHFR Vitamin B deficiency study1
1. Genotype profiles
Baseline LMF
Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med. 2010 Dec 23; 2:e20.
1Results are not statistically significant and are intended as a pilot demonstration of citizen science genomic studies
Baseline+ LMF
Centrum
Homocysteine umol/l
Centrum
LMF = L-methylfolate
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11July 19, 2011DIYgenomics.org
Athletic performanceCategory Genes V % S
Endurance, power, and energy
Endurance ACE, ACTN3, ADRB2/ ADRB3, BDKRB2, COL5A1, GNB3 7 50 22
Power ACE, ACTN3, AGT 3 50 8
Energy HIF1A, PPARGC1A 3 25 9
Musculature, and heart and lung capacity
Muscle fatigue and repair HNF4A, NAT2 and IL-1B 5 40 4
Strength HFE, HIF1A, IGF1, MSTN GDF8 5 17 15
Heart and lung capacity CREB1, KIF5B, NOS3, NPY and ADRB1, APOE, NRF1 9 36 11
Metabolism, recovery, and other
Metabolism AMPD1, APOA1, PPARA, PPARD 5 50 9
Recovery CKMM/CKM, IL6 2 50 5
Ligament and tendon strength
Ligament strength COL1A1, COL5A1, CILP 3 50 4
Tendon strength COL1A1, COL5A1, GDF5, MMP3 7 63 5
Image credit: http://www.istockphoto.com
V = number of variants; % = ratio of favorable polymorphisms to total alleles for a sample individual; S = number of studies
Source: Swan, M. Applied genomics: personalized interpretation of athletic performance GWAS. Jan 2011.
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12July 19, 2011DIYgenomics.org
Preventive wellness
Personal uses of the personal genome Ancestry Carrier status Disease risk profiling Drug response Athletic performance capability Product response
Wellness profiling Cancer Immune system Aging
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13July 19, 2011DIYgenomics.org
Predictive wellness profiling: cancer
Proto-oncogene/tumor suppressor gene polymorphisms
Source: DIYgenomics
Image credit: http://utmb.edu
Alleles 23andMe alleles
Gene RSID Poss Unf Fav Poss Fav Ex p-value OR Case Ctrl Citation
TP531 rs1042522 CG C G CG G CG 0.77 1.23 685 778 Joshi 2010
TP53 rs1860746 GT T G n/a n/a n/a 0.04 1.47 6,127 5,197 Liu 2009
MDM22 rs2279744 GT G T GT T GT 0.91 1.27 685 778 Joshi 2010
MDM41 rs1380576 CG G C n/a n/a n/a 0.95 1.03 4,073 n/a Sun 2010
HAUSP1 rs1529916 AG G A n/a n/a n/a 0.07 1.05 4,073 n/a Sun 2010
PTEN1 rs701848 CT C T CT T CT 0.00 0.12 53 107 Hosgood 2010
PTEN1 rs1903858 AG G A AG A AA 0.01 0.13 53 107 Hosgood 2010
BCL22 938C>A AC A C n/a n/a n/a 0.05 n/a 40 40 Fingas 2010
GNB32 rs5443 CT T C CT C CC 0.05 n/a 40 40 Fingas 2010
MYC2 rs6983267 GT G T GT T TT 0.00 1.21 930 960 Tomlinson 2007
MYC rs1050477 AC A C GT G GG 0.00 1.17 7,480 7,779 Zanke 2007 MYC rs7014346 AG A G AG G GG 0.00 1.19 14,500 13,294 Tenesa 2008
1Tumor Suppressor, 2Proto-oncogene
TP53: cell cycle arrest, PTEN: cell cycle progression modulator, MYC: cell cycle regulator
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14July 19, 2011DIYgenomics.org
Lung cancer risk and drug response
Risk and drug response for specific cancers
Source: Swan, M. Review of cancer risk prediction in direct-to-consumer genomic services. (poster) Canary Foundation Early Detection Symposium, May 25-27, 2010, Stanford University, Stanford CA.
Image credit: http://www.xianet.net
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15July 19, 2011DIYgenomics.org
Wellness profiling: immune system
Immune system genomic wellness profiling Immune response: T-cell activation
CTLA4, CD226, CD86, IL3
Source: DIYgenomics
Alleles 23andMe alleles
Gene RSID Poss Unf Fav Poss Fav Ex p-value OR Case Ctrl Citation CTLA4 rs231775 A/G A G AG G AA 0.007 0.642 172 145 Duan 2010 CTLA4 rs5742909 C/T C T CT T CC 0.098 0.67 172 145 Duan 2010 CTLA4 rs733618 C/T C T CT T TT 0.041 4.62 269 395 DallaCosta 2010 CD226 rs763361 C/T T C CT C CC 0.000 1.22 1,990 1,642 Dieudé 2010 CD86 rs1129055 A/G G A AG A GG 0.006 0.51 269 395 DallaCosta 2010 IL3 rs181781 A/G A G AG G GG 0.041 0.55 60 270 Lee 2010 IL3 rs2073506 A/G A G CT C CC 0.009 0.32 60 270 Lee 2010 IL3 rs40401 C/T T C CT C CC 0.014 2.18 60 270 Lee 2010
Image credit: http://www.iayork.com
CTLA4: T-cell inhibition; IL3: growth-promoting cytokine
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16July 19, 2011DIYgenomics.org
Aging: TA-65, telomere length & TERC mutation
Herbal supplement TA-65 (astragalus root) taken by 1000 people worldwide. Telomere and immune system benefits in humans published Mar 2011.1
TERC (RNA gene that extends telomeres) SNPs: rs10511887, rs12696304, rs16847897, rs2293607,
rs610160
1Source: Harley CB, et al. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Res. 2011 Feb;14(1):45-56.
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17July 19, 2011DIYgenomics.org
Aging: applied healthspan engineering
Representative Rational Healthspan Interventions Target=process Intervention
1 Blood pressure Multiple; exercise, dietary, sodium restriction, see RAS (below)2 Heart rate Exercise, vagal nerve stimulation3 Dyslipidemia Fish oil; flaxseed oil, olive oil niacin, statins 4 Renin–angiotensin system (RAS) Exercise, dietary, sodium restriction, ACE inhibitors, ARBs, renin inhibitors5 Medial elastocalcinosis Vitamin K2 6 Glucose homeostasis Exercise, metformin, dietary-caloric restriction 7 mTOR pathway Resveratrol, rapamycin, dietary-caloric restriction 8 Inflammation Aspirin, NF-kB inhibitors (e.g., EGCG, quercetin, etc.) 9 Autophagy Verapamil, trephalose, others
10 Extracellular matrix cross-link Alagebrium, ALT-71111 Chemopreventive Aspirin, bioflavonoids
Source: Larrick JW, Mendelsohn A. Applied Healthspan engineering. Rejuvenation Res. 2010 Apr-Jun;13(2-3):265-80, Table 2.
Legend: ACE, angiotensin converting enzyme; ARBs, angiotensin receptor blockers; EGCG, epigallocatechin 3-gallate; mTOR, mammalian target of rapamycin.
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18July 19, 2011DIYgenomics.org
Personal health collaboration studies
More information: www.DIYgenomics.org www.DIYgenomics.org/DIYgenomics_poster.ppt
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19July 19, 2011DIYgenomics.org
Study design template: MTHFR example
Source: http://diygenomics.pbworks.com/http://diygenomics.pbworks.com/w/file/36469280/DIYgenomics+study+design+template+blank.doc
CyanocobalaminImage credit: http://wikimedia.org
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20July 19, 2011DIYgenomics.org
Health hackers need Blood Tests 2.0
Low-cost home-administered self-read finger-stick blood, urine, saliva tests:
Traditional blood tests (Homocysteine, Vitamin B-12, Folate, Vitamin D, Creatinine, eGFR, Cortisol, Calcium, Iron, Aldosterone)
Hormones (Estrogen, Progesterone, Testosterone, Estradiol)
Immune system: CD4, CD8/CD28 ratio, IL-1, IL-6 Chemical / heavy metal burden: mercury, cadmium,
lead, tin
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21July 19, 2011DIYgenomics.org
Towards an epistemology of citizen science
Provide a structure and context for self-derived health knowledge
Q1: Are new kinds of knowledge are being formed through group collaborations such as wikipedia and health social networks?
Q2: Are there differences in the types of knowledge generated by traditional medicine, self-experimentation, and health collaboration communities?