DNA Testing: Living Longer Via Personal Genomics

DNA Testing: Living Longer Via Personal Genomics

Melanie Swan+1-650-681-9482

@DIYgenomics www.DIYgenomics.org

[email protected]

October 10, 2010

Slides: http://slideshare.net/LaBlogga

2October 10, 2010DIYgenomics.org

Numerous useful applications of genomics

Ancestry

Pregnancy screening

Identity (paternity, forensics)

Health conditions

Pharmaceutical response

Athletic performance

Aging profile

Image credit: http://www.uchsc.edu/vivat/2006/September2006/images/DNA_strand.jpg


Example: what to do with your data

Check if you have the risk allele for the BDNF gene Determine related SNP/rsID#, rs6265 (neuroplasticity) Search genomic data for rs6265 genotype (e.g., CC) Determine the risk allele (which letter?) (e.g.; G1) Opportunity: genomic database with three minimal fields:

gene, rsid# and risk allele Current genomics search resources

PharmGKB, dbSNP, GWAS catalog, SNPedia

Source: http://www.wired.com/wiredscience/2009/10/genetically-bad-driving1Ribeiro, L. et. Al., The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in

Mexican-Americans. Cellular, Molecular and Developmental Neuroscience. May 8, 2007.


Finding your BDNF data, variant rs6265

Consumer genomic services genotype 600,000-1m variants but only map a few up to the annotation browser


Conflicting consumer genomic test results

Source: http://dnasnips.com/dnaSnips/Heart.html


DIYgenomics: genomic service comparison

Companies use Different genes/variants Different population averages Different quantitative scoring methodologies

Risk for top 20 Health Conditions

Response to 250 Drugs

Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, May;12(5):279-8. http://www.diygenomics.org/webapp/gen_data.php

Private data upload: Marat Nepomnyashy; https://addons.mozilla.org/en-US/firefox/addon/156946/


DIYgenomics app - Android

Side-by-side comparison of consumer genomic services by loci and variants for top 20 conditions

Application developed by: Michael Kolb, Lawrence S. Wong, Melanie Swan


DIYgenomics app - iPhone

Side-by-side comparison of consumer genomic services by loci and variants for top 20 conditions

Application developed by: Ted Odet, Greg Smith (ManyFriends.com)


Drug response


Athletic performance

Power/endurance (sprinter or marathoner) ACTN3 rs1815739 CC (power), TT

(endurance); ACE rs1799752 DD (power), II (endurance)

Ligament injury Favorable genotype: COL5A1 rs12722 CC

and GDF5 rs143383 GG Head injury

Two copies of ApoE ε4 (rs429358, rs7412) suggest slower recovery from head injuries

Strength Favorable genotype: H1F1A rs11549465 TT,

HFE rs1799945 GG, and HFE rs1800562 AA

Increased HDL in response to exercise Favorable genotype: IL-6 rs1800795 GG

http://www.genome.duke.edu/education/seminars/journal-club/documents/Assael_2009.pdf

More information: DIYgenomics.org Athletic Performance


DIYgenomics study #1: MTHFR

Do common mutations in the MTHFR gene prevent vitamin B from working correctly?

Test whether 2 variations in the MTHFR gene (methylenetetrahydrofolate reductase) 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: nutritional deficiencies and symptoms associated with diabetes

complications, including vascular damage and nerve damage 50% or more of the population may have some form of MTHFR

polymorphism

Source: http://diygenomics.pbworks.com/MTHFR


MTHFR pathway diagram

Aaron Vollrath; http://bit.ly/cHRzS8

Legend: where interventions impact the pathway1 = Regular B-vitamin2 = Active form of B9 (folate)


DIYgenomics 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


MTHFR pilot study results

Average drug store vitamin (Centrum multivitamin) reduced homocysteine levels for 4/5 participants

Blood Test #

2. Homocysteine levels

DIYgenomics MTHFR citizen science study1

1. Genotype profiles

Baseline LMF

Source: http://diygenomics.pbworks.com/MTHFR_Results

1Results are not statistically significant and are intended as a pilot demonstration of citizen science as a model

Baseline+ LMF

Centrum

Homocysteine umol/l

Centrum


Boston University: Genetic Signatures of Exceptional Longevity in Humans

Source: Sebastiani P et al. Genetic Signatures of Exceptional Longevity in Humans. Science. 2010 Jul 21. http://diygenomics.org/citizengenomics/bu_longevity.php


DIYgenomics aging study

Genomics + physical biomarkers + intervention Top twenty genomic mechanisms of aging

1. Aging-specific genetics

2. Diabetes and metabolic disease

3. Catabolism (waste removal) and other

4. Heart disease and blood operations

5. Cancer

Top twenty phenotypic biomarkers of aging Interventions

Traditional Novel

More information: http://diygenomics.pbworks.com/Aging

Image credit: http://www-nmr.cabm.rutgers.edu


DNA sequencing: 10x/yr improvement

April 1, 2010 Image credit: http://pubs.acs.org/cen/_img/87/i50/8750cover2_law.gif Dec. 14, 2009


Direct-to-Consumer genomics landscape

Single/few condition Multiple condition Whole genome

Cost

1Medical condition $9,500 Service Breadth

Public studies MatchmakingScientificMatch $1,995GenePartner $10-$99

PaternityGenelex $200-$475Identigene $149-$399

Pregnancy ScreeningCounsyl $349

NutrigenomicsAPO E Gene Diet $389Inherent Health $99

Coriell15 conditions

Scripps (Navigenics)28 conditions

Pers. Genome Proj.Conditions undisclosed

Harvard Med. Sch.

Genetic disorders,

PredispositionDNA Direct $200-$3,500Matrix Genomics $199-$799

Drug sensitivity,

$

Exome

23andme174 conditions

Navigenics*40 conditions

deCODEme49 conditions

$1,000

$429$299

Genomics71 conditions

Pathway*

$2,500

$999 $2,000

$985 *Must be physician-ordered

Knome

EdgeBio$6,000

$19,500

Knome

Illumina$48,000

$350,000

$99,500

$68,500

$20,0001

$39,500


Genomics comparison scorecard

Consumer genomic service

# Cond-itions

Cost Report Data access

Visible research quality1

Updates

deCODEme 49 $2,000 + + +23andme 174 $429 Navigenics 40 $999 Pathway Genomics 71 $299 Coriell 7-15 public

study

PGP (Personal Genome Project)

n/a public study

1Conditions, genes, variants, underlying research references, and methodology white paper(s) available on public website

Which service to buy?

Melanie Swan+1-650-681-9482

@DIYgenomicswww.DIYgenomics.org

[email protected]

Slides: http://slideshare.net/LaBlogga

Creative Commons 3.0 license

Thank you! Questions?

DNA Testing: Living Longer Via Personal Genomics

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