Need for systems approaches to dissect environment and genetics in disease

1. P = G + EType 2 Diabetes
Cancer
Alzheimer’s
Gene expression
Phenotype Genome
Variants
Environment
Infectious agents
Diet + Nutrients
Pollutants
Drugs
Chirag Patel
@chiragjp
3/1/19
NCI Systems Epidemiology workshop

2. Lakhani et al, Nature Genetics 2019http://apps.chiragjpgroup.org/catch/
56K twins and 700K siblings in a massive health insurance cohort
point to complex and elusive variation in 560 phenotypes
https://rdcu.be/boZeV
Chirag Patel
@chiragjp
3/1/19
NCI Systems Epidemiology workshop

3. 56K twins and 700K siblings in a massive health insurance cohort
point to complex and elusive variation in 560 phenotypes
560phenotypes
Nature Genetics 2019http://apps.chiragjpgroup.org/catch/
h2=0.3 (🧬)
c2=0.1 (🏠)
?
https://rdcu.be/boZeV
Chirag Patel
@chiragjp
3/1/19
NCI Systems Epidemiology workshop

4. 🐘
Chirag Patel
@chiragjp
3/1/19
NCI Systems Epidemiology workshop

5. Elephant in the room (full of system epidemiologists):
Is all cancer risk random?
Tomasetti and Vogelstein Science 2015
Chirag Patel
@chiragjp
3/1/19
NCI Systems Epidemiology workshop

6. • What techniques, cohorts, and data
measurement modalities to capture non-genetic
variation in populations?
• Does it matter?
• Is it possible to develop approaches to partition
genetic vs non-genetic vs random chance in
disease variation?
• What is “error” vs. true non-genetic signal?
Chirag Patel
@chiragjp
3/1/19
NCI Systems Epidemiology workshop