1. Dr. Layla Jader Consultant in Public Health Genomics 6 & 7 November 2014 Cardiff The Second Annual Course on The Impact of Genomics on Public Health Epigenetics should be shaping our public health policy

2. The main determinants of health (Dahlgren and Whitehead, 1991)

3. General socioeconomic conditions The wider environment Individual life style factors Genomics We & our genes are more flexible than we ever thought before

4. A study evaluated methylation in healthy men exercising 1.8 hours /week for 6 months Waist-hip ratio ↓ with ↑methylation of a gene previously associated with waist-hip ratio, Significant methylation changes were also observed in 18 candidate genes previously associated with obesity & 21 genes associated with Type II Diabetes Examples- Exercise, obesity & Diabetes

5. Meta analysis of data on 240,000 people from 54 studies in adults & children on FTO gene Carriers of 2 FTO ‘fattening’ gene variants had a 23% higher risk of obesity But if they were physically active their risk is lowered by 30%. Our genes are not our destiny!

6. Smoking & obesity A study has assessed paternal smoking & obesity on markers of DNA damage or instability in cord blood of their offspring. They tested blood cells, spermatozoa & cord blood from 39 family trios & identified transgenerational DNA changes in offspring of smoking fathers. Hypomethylation at IGF2 (Insulin like growth factor 2) gene in umbilical cord blood has been found to be associated with paternal obesity.

7. Pregnancy At embryological development, epigenetics controls how & when certain genes are turned on & off to help the body grow & develop into various tissues forming different organs

8. Epigenetics in normal human development 3 generations at once are exposed to the same environmental conditions (diet, toxins, hormones, etc.). University of Utah Genetics Science Learning Centre Website

9. Diethylstilbestrol (DES) exposure in the uterus Given to pregnant women to reduce risk of miscarriage 1930s-1970s Women exposed prenatally developed structural anomalies of reproductive tract, menstrual irregularity, infertility, miscarriages & increased risk of Gynae cancers especially vaginal cancer. These abnormalities have been replicated in mouse model.

10. The granddaughters also showed menstrual irregularities & infertility Similar studies in mice have shown the same outcomes in female descendants. DES is a teratogen & carcinogen in humans Possible transgenerational effects were proposed by the researchers

11. Transgenerational inheritance to 4 th & 5 th generations has been directly observed in rats. Cambridge researchers have also found that some rare methylation can ‘escape’ the reprogramming process & can thus be passed on to offspring revealing how epigenetic inheritance could occur.

12. So, what are the epigenetics implications to Public Health Policy?

13. 1.We now have evidence at the molecular level confirming that positive life style & environmental changes lead to epigenetic modifications that can lead to improved health outcomes. 2.Research findings in this area are increasing in an exponential manner & public health professionals need to catch up with their important significance to their practice.

14. 3. These advances are shedding light as to where our public health priorities should lie. 5. Health of mothers during pregnancy is hugely important, not only for her own future health & the health of her foetus & his future health as a child & as an adult but also for the future health of her grandchildren (reproductive cells) (3 generations)

15. 6. The health of growing children especially in mid childhood & pre-puberty is of paramount importance for the child & as he/she become an adult & for their future pregnancies & children. 7. Early embryonic development & mid childhood are the epigenetics plasticity period when the body is very susceptible to outside environmental factors 8. There is a total scientific agreement that support the above statements.

16. Although we cannot change our genome, we can change our epigenome through life style changes & through ameliorating environmental factors

17. Health outcome First Intervention Effect of same 1 st intervention The Health economic argument is strong Continuous Favourable Environment

18. Child development is the most important & cost effective time to intervene & prevent diseases Timely intervention produces substantial risk reduction Life course Risk of chronic diseases Impact of adult intervention is small Fixed genetics contribution to risk + Environmental influence in utero Birth

19. Inequality in early cognitive development of children in the 1970 British Cohort Study, at ages 22 months to 10 years IQ heritability 50-80%

20. Transgenerational research findings in mammals suggest that the impact is more than just 3 generations There are disagreements on this among scientists  As to how often it does happen & for some, if at all  Whether epigenetics is the basis or another genetic mechanism. Environmental, social & economic factors not only influence the health of the present generation but if adverse they can blight future generations

21. A downward spiral may continue through genome alterations, perpetuating the ill health cycle This gives inequalities in health a new challenge, a new dimension & an added urgency to change our policy

22. It emphasises the need for a public health policy that prioritises early life from before pregnancy up to puberty. This should cover ALL children & ALL aspects of their lives (physical, emotional, material, social & cultural) Maternal & child health programmes have to be annually accepted as number 1 priority.

23. Improve foetal health & Childhood health Healthier children & grandchildren Improve health of the whole nation Improve education of parents & education of children Improve employment & chances of social mobility Improve the economy & prosperity Reduce inequalities in health

24. Public services like health & education have direct access to the ‘theatres of actions’ (antenatal services, social services, nurseries & schools), Also direct access to a captive audience (mothers, babies, toddlers & school children). Adhering to the principle of ‘Sustained Synergy of Intertwined Actions on Both Children’s Health & Education’. The total outcome will be more than the sum of health plus education as one strengthens & magnifies the other.

25. Develop an integrated & comprehensive strategy Antenatal clinics MidwivesPre-schoolSchool A captive audience Health Visitors School Nurses Safe Havens Public Health & Wellbeing Agents Sustainable synergistic actions on both health & education

26. We should raise the bar in all quality aspects of health & educational systems

27. This means raising the bar  When assessing the quality threshold of standards of health & education systems  In selection of students entering professional career training programmes Such a government policy prioritising health & education have to be the centre stage of government priorities for many years, irrespective of which political party is in power

28. Only a sustained & consistent approach will ensure better outcomes It has implications to other policies & employment laws concerning maternity, child care & child protection as it reinforce their values. Future policies in these areas must reflect the new knowledge that considers  pregnancy as an incubator of future generations &  children as the guardian of our future genome.

29. Improve health Reduce inequalities in health Improve social mobility Improve the economy The new Strategy will Will take a decade or two to be achieved

30. ‘Children’s Prioritisation Act for Wales’ Advocate for the establishment of a new ‘Children’s Prioritisation Act for Wales’ To complement existing laws & measures concerning children & the rights of the child, but going further To create new duties for public bodies (& where possible voluntary & private bodies) to prioritise meeting maternal & childhood needs.

31. Only such a Bill will fully achieve our aims in improving the nation’s health & prosperity It shows that strong convincing evidence have been sought & found. It shows unity of purpose for the whole country It obliges ministers, organisations, groups & individuals to give it its rightful place. It will raise the society’s awareness, changing the culture & attitudes which are pre-requisite of any big societal change that is required to give children their rightful place in society.

32. Will ensure wide coverage of this important area Gives it the gravitas it deserves It will strengthen other child laws A bill that follows the example of Scandinavian countries in being broad in nature that create conditions for children’s health & education to be at the forefront of policies in every governmental department & every public, private & voluntary organisation will reduce inequalities in health in Wales.

33. Sustainable Future Generations Bill now renamed ‘Well Being Future Generations Bill’ Royal Ascent in April-May 2015 A new policy based on cutting edge science will be the best sustainability initiative we can device for our ‘Future Generations’ What is the use of ensuring a sustainable planet around us if we are unable to live healthily & long enough to enjoy it?

35. Our children are our future