1. EMGO Institute for Health and Care Research Quality of Care Martina Cornel Professor of Community Genetics & Public Health Genomics Genomics in health care: state of the art in 2013 Community Genetics, Dept Clinical Genetics CSG symposium: Exploring dilemmas of genomic health information in private life insurance Utrecht, NL 28 March 2013

2. 2000: genome sequence published Without a doubt, this is the most important, most wondrous map ever produced by humankind. With this profound new knowledge, humankind is on the verge of gaining immense, new power to heal. Genome science will have a real impact on all our lives -- and even more, on the lives of our children. It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases. Human genome project 2000

3. Genetics: “bench” or “bedside”? Science or health care? Left: Watson and Crick describe the structure of DNA Above: Breuning explains the consequences

4. >10 years after … Results in health care modest Genetic variants (SNPs) explain only minority of interindividual risk differences The human molecular system is more complex than anticipated.

5. FS Collins, 2010, Nature: we invariably overestimate the short-term impacts of new technologies and underestimate their longer-term effects

6. Finding the missing heritability.. Manolio, Nature 2009

7. Genomics has not revolutionized medicine Promises too optimistic –GWAS, SNPs predict less than expected Complexity of human biological system Lack of translational studies

8. Prevention advice in 2020?

9. Premature translation??

11. Professional policy development in genetic health care: the challenge of discerning hopes from hypes

12. Genetic risk related to life insurance Risk of (sudden or early) death –Monogenic subtypes of common disorders –Multifactorial etiology of disease –Whole genome/exome sequencing Interventions possible –After test & intervention reduction of premium? Fear for consequences of genetic testing for insurance

13. Long QT syndrome

14. Guidelines in cardiogenetics www.youtube.com/watch?v=52RJWyjogY0&feature=related www.youtube.com/watch?v=DU_i0ZzIV5U&feature=related

15. Cancer & genetics Familial cancer FAP, HNPCC BRCA1 & 2

16. Burn J, Lancet, 2011 Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19-0·86, p=0·02) and an IRR of 0·37 (0·18-0·78, p=0·008). INTERPRETATION: 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment.

17. Family history and DNA in cascade screening? Extend programs aiming to diagnose monogenic subtypes (as cascadescreening FH)? HNPCC FAP BRCA HCM LQTS ARVD MODY hemochromatosis

18. High vs. lower predictive value Janssens 2006

19. Genetic risk related to life insurance Risk of (sudden or early) death –Monogenic subtypes of common disorders –Multifactorial etiology of disease –Whole genome/exome sequencing Interventions possible –After test & intervention reduction of premium? Fear for consequences of genetic testing for insurance

20. Improvement of Risk Prediction by Genomic Profiling Mihaescu 2010 Am J Epidemiology, Modelling study, multiplicative interaction many gene variants. Classical risk model: age, blood pressure, cholesterol, smoking etc.

21. Whole genome/exome sequencing March 2013

22. Minimum list ACMG

23. Mainly autosomal dominant conditions 50% risk for first degree family members Oncogenetics, cardiogenetics “opportunistic screening” (if for any reason WGS is performed, also seek and report these variants) In all subjects, irrespective of age, excl fetal samples We recognize that there are insufficient data on clinical utility to fully support these recommendations…

24. Genetic risk related to life insurance Risk of (sudden or early) death –Monogenic subtypes of common disorders –Multifactorial etiology of disease –Whole genome/exome sequencing Interventions possible –After test & intervention reduction of premium? Fear for consequences of genetic testing for insurance

25. Predicting genetic risk Increasingly possible for rare monogenic conditions where interventions are possible (e.g. colonoscopy and aspirin to prevent cancer mortality in Lynch syndrome) If prognosis is better – no reason do differentiate for life insurance? For common multifactorial disorders: no news

26. Genetic risk related to life insurance Risk of (sudden or early) death –Monogenic subtypes of common disorders –Multifactorial etiology of disease –Whole genome/exome sequencing Interventions possible –After test & intervention reduction of premium? Fear for consequences of genetic testing for insurance

27. Fear for insurance AOP Henneman et al. EJHG 2013

28. Conclusion New possibilities to identify rare monogenic variants associated with oncogenetic & cardiogenetic risks, and are actionable Identification of these will an average lead to risk reduction, therefore no need to ask before life insurance For common disorders with multifactorial etiology: no news But “the public” fear is that solidarity is at stake

29. THANK YOU FOR YOUR ATTENTION