1. P3G: an international consortium in Human Genome Epidemiology
Ultimate Goals: For the understanding of gene-environment causes of chronic diseases For better public health strategies

2. The Causal Complexity of
Chronic Diseases
Diabetes
Asthma
Heart Disease
Schizophrenia
Cancer
Multiple Sclerosis
Obesity
Arthritis
Genetics
Environment
Diet & Lifestyle
Social
Structure
Most common disease in technologically advanced societies are multifactorial in origin. They are the product of interaction between our genetic endowment and the world around us acting over a human lifetime.
“webs of causation”

3. Why Study Gene-Environment Interactions?
Obtain a better estimate of the population attributable risk for genetic and environmental risk factors by accounting for their joint interactions
Strengthen the associations between environmental factors and diseases by examining these in genetically susceptible individuals
Help dissect disease mechanisms by focusing on biological pathways most relevant to that disease, and environmental factors most relevant to the pathway.
Determine which specific compounds in a complex mixture of chemicals (from pollution, diet, etc.) cause disease.
Use the information to design new preventative and therapeutic strategies
Offer tailored preventive advice that is based on the knowledge of the genetic profile of an individual.
Hunter, Nature Reviews/Genetics 2005

4. Resources needed for identifying genetic risk factors and gene-environment interactions affecting the predisposition to chronic diseases
Comprehensive knowledge of genetic variation
Genotyping Technologies
Cohorts - Phenotypes
- Exposures
- Large Size
Analytical Tools
HapMap
P3G

5. Example of Sample Size Issue for detecting ONE interaction for a dichotomous trait and a 10% exposure
Hunter, Nature Reviews/Genetics 2005

6. What 10,000 incident cases in a gene-environment study can provide:
(with power calculations that that take into account considerations of misclassification of exposure and outcome data, and realistic data collection scenarios)
For genotypic and environmental prevalences of 10% and above, 10,000 cases will provide adequate power for interaction effects with an MDOR greater than 2.
(MDORs; defined as the smallest odds ratio that can be detected at p=10-4 and power=80%).
Paul Burton, UK BioBank Technical Report 2005

7. What 10,000 incident cases in a gene-environment study can provide:
(with power calculations that that take into account considerations of misclassification of exposure and outcome data, and realistic data collection scenarios)
2. For a genotypic prevalence as low as 1% there will be adequate power to detect substantial (OR between 2 and 3) direct genetic effects. For this low genotype prevalence, gene-environment interactions will only be detectable for very large interaction effects (e.g. OR > 7).
3. 10,000 cases will provide a powerful platform for genome-wide indirect association studies (requiring rigorous definition of statistical significance of p<10-7).
Paul Burton, UK BioBank Technical Report 2005

8. How long does it take to reach 10,000 cases in a cohort with 500,000 cases?
Breast cancer (F)
17 yrs
Colorectal cancer
22 yrs
Prostate cancer (M)
Lung cancer
34 yrs
Stroke
18 yrs
MI and coronary death
8 yrs
Diabetes mellitus
6 yrs
COPD
13 yrs
Hip fracture
21 yrs
Alzheimer’s disease
Parkinson’s disease
23 yrs
Paul Burton, UK BioBank Technical Report 2005

9. Public Population Project in Genomics
A consortium dedicated to fostering international collaboration between researchers and projects in the field of population genomics

10. P3G: History and Launching Phase (2003-2005)
International meetings leading to the creation of P3G:
2003: London, Montreal, Manchester
2004: Helsinki, Tallinn, Toronto
Supported by: Wellcome Trust, European Union
Genome Canada and Genome Quebec
Non-for-profit organization incorporated in 2004
Secretariat and Observatory created February 2005
Seed money from Genome Quebec and Genome Canada for the launching phase
Incorporated in 2004… but the project goes back to 2002
A small secretariat offers adminsitrative support and lead some of the work required to fulfill the need of P3G members. It also houses the P3G Observatory.

11. P3G mandate
create a network in population genomics that will comprise over 3 million participants for epidemiological studies
provide statistical power for analysing complex genetic and environmental determinants of health and disease
leverage the combined expertise of hundreds of researchers around the world
promote communication among national and international organizations
increase the ability to share and generate new knowledge dedicated to improve public health and welfare.

12. P3G Consortium Model
An international resource for the coordination and exchange of ideas and data that will be generated by the various population biobanks
Kora-Gen
LifeGene
(Sweden)
(Germany)
Generations
NHLBI
(Scotland)
(USA)
(Europe)
(Canada)
Genoma Espana
NIGM
(Mexico)
(Spain)
Danubian Biobank Foundation
CIGMR
WAGHP
(Australia)
(UK)
(Europe)
LifeLines
ALSPAC
(Netherlands)
(UK)

13. P3G Membership 3 3
Regular Member
Associate Member
Individual Member

14. NEED FOR HARMONIZATION
Analogie: Bill Ollier

15. HARMONIZATION IS NOT REGIMENTATION

16. P3G Operational Chart Funders Auditors P3G General Assembly
P3G Board of Directors
P3G
Secretariat
P3G Steering Committee
IWG 1
(Social/Clinical/
Environmental)
IWG 2
Informatics
IWG 3
Ethics and
Governance
IWG 4
Epidemiology/
Biostatistics
Core
Core
Core
Core
Here is the operational chart of P3G’s
P3G is a membership –based organization
It should be noted that population biobanks who become regular members keep their own governance structure and their administrative and scientific independence. However, they join a network where they will find and develop common scientific and ethics research resources, with an aim to foster harmonization. Each biobank is free to include these tools in their strategy.
Core
Core
Core
Core
Core
Core
Core
Core
P3G OBSERVATORY

17. International Working Groups (IWGs), leaders and early outcomes
Social, Environmental and Biochemical Investigations
Leader:
H. Erich Wichmann (KORA-Gen, Germany)
-Common Core Variables for Population Based Studies
-Common DNA Quality and Quantity Control
-Conceptual model for harmonization of physiologic and biochemical measures
Knowledge Curation And Information Technology
Jan-Eric Litton (LifeGene, Sweden)
-Nomenclature Working Group
-Protocols for Data Sharing
-Biobank lexicon
Ethics, Governance and Public Engagement
Alastair Kent (Genetic Interest Group, UK)
-Intellectual Property Policy
-Consent form Inter-operability
Epidemiology and Biostatistics
Muin Khoury and Julian Little (CDC)
-Leader was just appointed: first meeting in September
IWG are composed of 1 expert from of each of our regular members (i.e. population based biobanks) and P3G members who are experts in the field
There are four IWG covering 4 key topics
EACH IWG is t

18. P3G Cores Principal work units of P3G, Self-funded,
Focused on specific issues related to biobanks,
Cores activities are reported to IWG regularly
2006 goals to create cores in areas such as:
Questionnaires and
Clinical Measures
Population Genetics
And Policymaking
DNA/SNPs and
Genotyping
Nomenclature
Laboratory
Phenotypes
Impact of
Commercialization
Environmental
Assessment
Federated Databases
Statistics and
Epidemiology
Participation: Gender
Age, Ethnic Differences

19. McGill University and Genome Quebec,
The P3G Observatory: a web-site describing Biobanks and Population Genetic Studies
Isabel Fortier, Ph.D.
Vincent Ferretti, Ph.D.
Denis Legault, MPA
McGill University and Genome Quebec,
Innovation Center
740 Dr. Penfield Avenue
Montreal (Qc) H3A 1A4

20. The P3G Observatory The Observatory contains:
a description of studies (57 as of May 29, 2006)
a catalog of questionnaires, consent forms, etc.
a search tool using key words for common variables used in genetic epidemiology
a companion tool for questionnaire development and harmonization between studies

21. 57 large population-based studies
Catalogue of Studies
A standard way to describe population studies in genomics
General Information
Background
Objectives
Methods
Status
Ethics and Governance
Available Documents
Publications
57 large population-based studies
(P3G members and non-members)
22 studies with complete information
35 studies with summary information

22. General Tools in Development
DESIGN OF STUDIES
BioBank lexicon
Ethics and governance “good practices” guidance documents
ETHICS AND GOVERNANCE
General reference procedures for:
Questionnaires development/collection;
Physiological measures collection;
Samples collection, manipulation, storage or analysis
INFORMATION COLLECTION/ TREATMENT
INFORMATION TECHNOLOGY
Open source information management system for Biobanks
Reference tools for statistical analysis and power calculation
DATA ANALYSIS

23. How do we get from here to there? Meta-studies enabled by P3G
From Biobanks to improving health and preventing disease:
How do we get from here to there?
Meta-studies enabled by P3G

24. P3G Future Research

25. P3G 2020 With the synergy of P3G:
The scientific community will benefit from having a powerful international resource for gene-environment studies of complex diseases
Return of investment will be quicker, more efficient and of higher quality through international harmonization
Health Care Systems will benefit from accurate information for designing and implementing population health strategies

26. MERCI Bartha Knoppers, Leena Peltonen, Andres Metspalu, Bill Ollier,
Eric Wichmann, Jan-Eric Litton, Julian Little, Muin Khoury, Alistair Kent, Lyle Palmer, Thomas Hudson, Paul Burton,
Claude Laberge, Isabel Fortier and Mylene Deschenes,