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Quantified self ignite talk. Redesigning biology may be man's ultimate artistic and scientific exploit. The first steps are reading and writing genetic data with DNA sequencing and synthetic biology. Already human genome sequencing costs have declined such that individuals worldwide are accessing their own genomic data, and can explore it through open-source science communities such as DIYgenomics.
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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
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
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.
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+ + =
5July 19, 2011DIYgenomics.org
DTC genomics – interpretation variance
Private data upload: Marat Nepomnyashy; https://addons.mozilla.org/en-US/firefox/addon/156946
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
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
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.
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
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
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.
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
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
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
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
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.
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.
18July 19, 2011DIYgenomics.org
Personal health collaboration studies
More information: www.DIYgenomics.org www.DIYgenomics.org/DIYgenomics_poster.ppt
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
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
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?