1. General considerations on genetic collaborations in PSC
Immunochip project
&
General considerations
on genetic collaborations in PSC
Tom Hemming Karlsen, MD PhD
Clinic for Specialized Medicine and Surgery
Oslo University Hospital, Rikshospitalet
Oslo, Norway
Vienna, EASL 2010, April 16th

2. Shared and unique genetic risk
Zhernakova et al., Nat Rev Genet 2009

3. Interpretation and translation
GeneA
GeneB
Drug?
GeneC
GeneD
Disease e.g. PBC or PSC
GeneE

4. Detection and translation of genetic risks
Shared genetic risk:
Association studies
Large study populations
General mechanisms & general therapeutics
Disease-specific genetic risk:
Deep sequencing / mutational characterisation
Extremely well-characterized populations/families
Disease specific mechanisms & specific therapy

5. Detection and translation of genetic risks
Shared genetic risk:
Association studies
Large study populations
General mechanisms & general therapeutics
Disease-specific genetic risk:
Deep sequencing / mutational characterisation
Extremely well-characterized populations/families
Disease specific mechanisms & specific therapy

6. Immunochip Dedicated Illumina array (Jeffrey Barrett)
Wellcome Trust / Sanger Centre initiative
200,000 SNPs at genes already found to associate with different inflammatory conditions
10-15 inflammatory disease phenotypes
175, ,000 DNA samples
Purpose: define overlap in genetic risks between inflammatory diseases
Benefit for PSC: low hopes for PSC specific pharmaceutical initiatives

7. Challenging the genetics collaboration…
Sample size ~4000 within reach – but don’t stop!
- Nordic countries
- US/Canada
- UK
- Germany/BeNe
Funded by Norwegian PSC research center
Technical group - analysis group - writing group
PSC paper + participation in Sanger meta-analysis
Authorships: banner vs. semi-banner vs. individual
Data-management / return of data to contributors