Assessing Biological and Genetic Risk for Policy Priorities: A Community Perspective

1. Using assessments of biological and genetic risk to inform policy priorities: A community perspective Dr Pritti Mehta Programme Manager (Equity and Access) Genetic Interest Group

2. Key questions? • What factors cause ethnic inequalities in health? • To what extent do genetic risk factors contribute to population or ethnic differences in health? • Do concepts of race or ethnicity have any biological meaning? • How to use this information to inform policy priorities that will achieve beneficial societal outcome?

3. Understanding and tackling ethnic inequalities in health • Differential access to services • Quality of services • Social and cultural influences • Genetic/biological variation • Foetal programming • Migration • Life events • Socio-economic factors • Racial discrimination • Insufficient research to identify and address the underlying causes of variation

4. To what extent do genetic risk factors contribute to population or ethnic differences in health? • Mendelian disorders: such Sickle Cell Disease and Tay Sachs which have a clear genetic basis and show variation in prevalence across population or ethnic groups due to unequal distribution of the disease causing alleles • Multi-factorial common conditions: Although minority ethnic groups are often disproportionately affected - the genetic basis is still unclear and therefore need for further research to investigate gene –environment interactions in multiple populations in order to answer these questions

5. Do concepts of race or ethnicity have any biological meaning? • Meeting convened at the National Human Genome Centre at Howard University in Washington, D.C. on 15th May 2003 titled “Human Genome Variation and Race: The State of the Science”. Brought together experts in sociology, anthropology, history and genetics

6. Background • Advent of molecular genetics and sequencing of the human genome • Recent common genetic origin in Africa • Greater genetic variation within populations that between populations • These findings have lead to many well-intentioned statements by geneticists suggesting there is no connection between race/ethnicity and human genetic variation

7. Where the consensus lies? • Increasing scientific evidence that human genetic variation is geographically structured – most individuals form the same geographic region will be more similar to one another than to individuals form a distant region. • Genetic variation is continuous and overlapping and therefore populations are never pure with definite boundaries between individuals or populations (e.g. normally ascribed to races). • Rainbows within rainbows….. Groups identified by ethnic or geographic labels maybe genetically highly internally structured. • Worldwide patterns of genetic variation not well understood.

8. Where the dispute lies? • How to represent that portion of variation that does correlate with geography? • Because there is some correlation between geographical origin and ethnicity/race it would be misleading to say that there is no connection between ethnicity and genetic variation • However the connection is quite blurry because of multiple other non-genetic components of ethnicity, the lack of defined boundaries between populations and the fact that many individuals have mixed ancestry.

9. Francis Collins: US Director of the US National Human Genome Research Institute (NHGRI) • True understanding of disease risk requires us to go well beyond these weak imperfect proxy relationships; and • If we are not satisfied with imperfect surrogates in trying to understand hereditary causes, then we should not be satisfied with them as measures of environmental causation either.

10. Conclusions • Assessment of geographical origin, ancestry, or even race/ethnicity to determine genetic risk may in some cases prove biomedically useful. • However direct assessment of the underlying genetic variation will ultimately yield more useful information.

11. How to use this information to inform policy priorities • Translating these finding into policy principles will not be easy or straight-forward • Risk assessments based on population differences or ethnicity should be properly assessed, with attempts made to remedy situations in which the use of such information is misleading or couter-productive • Population affiliations alone maybe crude indicators e.g. failure to diagnose sickle cell disease in a European or cystic fibrosis in an Asian individual

12. How to use this information to inform policy priorities • Proper consultation with community groups to assess acceptability and the psychosocial impact of these risk assessments • However these debates should not hamper progress towards identifying new genetic knowledge that might benefit vulnerable groups: Such as the need to carry out well-designed, large scale studies in multiple populations to identify underlying disease risk factors

13. UK Biobank • UK Biobank: large scale prospective cohort study that aims to identify genetic and environmental influences on common disease • Planning to sample minorities in proportion to the total UK population • Will effectively exclude minorities because the numbers collected will not be sufficient to provide information about gene–environment interactions specific to those groups

14. UK Biobank • Ultimately this will prejudice our knowledge of the genetic and environmental determinants of disease and may lead to greater inequalities in health. • We strongly support Francis Collins view that over-recruitment of minorities is an essential component of any prospective cohort study of genes and environment. (Collins 2004).

15. Concerns • The inability to effectively inform policy and practice towards research and service delivery - • May indeed widen ethnic health inequalities that arise from biological/genetic variation, due to knowledge gaps and resulting differential access to diagnosis and treatment options

16. Responding to community specific needs • A recent study in a UK child development centre in Bradford found that the prevalence of many non-malignant life threatening conditions was almost double the national average. • Here 42% of births are of Pakistani origin

17. Communication of risk • Need to develop linguistically and culturally appropriate and accessible forms of communication to inform and raise awareness about different risk assessment programmes • Develop these through consultation with target groups • Note that concepts of risk can vary from individual to individual

18. Community consultation comments On cousin marriage: • ‘Make it clear, very sensitively so as to not sound like you are attacking individuals, cultures, religious beliefs, etc…, that inter-family marriage increases risk of recessive genetic diseases, but not dominant genetic diseases., But don’t exaggerate the risk.. Explain that it depends on the specific disease/ individual/ relationship between 2 specific people’ • ‘Must be very careful, as one misunderstanding can lead to the whole thing being misinterpreted, i.e., communities feeling as though you are attacking their particular culture’

19. Community consultation comments On pre-implantation diagnosis:  • ‘pregnancy termination is unthinkable for many people of different cultures and may be religions.  For Somalis in Somalia and of course many in here it is not an option.  The leaflet should clearly state that if you are carrying a foetus with genetic disorder, termination is not compulsory nor the only option’

20. Thank you