The role of genetic and environmental effects over the life-course

1. The role of genetic and environmental effects over the life-course Andrew Pickles University of Manchester Interdisciplinary approaches to studying inequalities in health and quality of life A joint meeting organised by the Wolfson Research Institute, the University of Durham and the ESRC Research Methods Programme

2. Ground-clearing Preconceptions and prejudices

3. Preconceptions and Prejudices • Social critiques still often anti-genetic diatribes using quotations from early 20th century ‘eugenicists’ • Assumptions that social explanations are benevolent while genetic explanations are intrinsically malignant. • but social explanations can be harmful • e.g. inadequate parenting as an explanation of childhood disorders such as autism

4. Preconceptions and Prejudices • We assume that our own judgements about genetics are neither time-bound nor in conflict with those most affected • the ‘gene’ for homosexuality

5. Preconceptions and Prejudices • There is nothing intrinsically racist about genetical explanations. Indeed if genetics tells us anything it is that races are genetically amazingly similar.

6. Genetic and Social Research However, this is not to say that all genetics research is good or should be believed. There is much poor quality work and naïve genetic determinism in the thinking of bio-medical researchers – they need the help of social scientists!

7. Genetics versus Social Explanations How can genetics be all important when: (1) Genetic differences between populations are tiny compared to the many mean differences in most measures. (2) Biometrical variance decompositions show little shared environment but we witness large social gradients. (3) Development is dynamic but DNA is static. (4) There are clear changes in population means over time (5) Development is socially responsive.

8. Genes versus Environment Limitations of ‘Main Effects’ Science: - both social and genetic Theoretical perspectives - interactionist perspective - life-course perspective - developmental perspective

9. Summary of Population Genetics Selection acts such that: • Any variant that reduces ‘fitness’ will tend to die out • High genetic variation to ‘new’ toxins e.g. drugs, BSE • Heterozygous advantage may maintain ‘risk’ alleles

10. Basic genetics • New Mutations - rare, often severe and thus frequently not passed on to the next generation. Not the focus of this talk • heritable ‘normal’ variation • Each child has ‘exactly’ 50% of the genes of each parent • Ordinary sibs on average share 50% of their genes • MZ twins share 100%

11. Standard Twin Analysis MZ=1,DZ=0.5 E A C C A E T1 T2 If A,C and E are equal for MZ’s and DZ’s then rmz-rdz=A/2 Difference in twin correlation reflects half the genetic variance

12. Adoption and Genetic Mediation sib, adoptee=0 sib,sib==0.5 E A C C A E A C E S1 S2 S3 sib sib adoptee X Putative environmental cause If dashed effect smaller than solid - effect of X reflects genes not environment

13. Summary of Twin/Adoption Findings • The overall effects of all shared environmental/between family differences are frequently non-significant (i.e. sociology not important) • Apparent effect of measured social variables can be largely genetically mediated i.e parental interest in education merely reflects parental genes and itself has no direct ‘effect’ on the child. • Non-shared environmental variance large (but often mostly measurement error)

14. Biometrical Genetics • Analytical Assumptions • Sophisticated models but non-normality can lead to bias • Shared environment assumption frequently thought suspect but actual evidence against is often modest • Analytical Practice Testing of implausible ‘null-hypothesis’ of c-squared=0 Inadequate use of confidence intervals Failure to pursue gene-environment interactions

15. Summary of Developmental Behavioural Genetics • There is little evidence for social processes acting over the course of development so as to become the dominant source of variation • There is considerable evidence for genes having an ongoing, sometimes increasing effect over time. ‘The genes will out’

16. A False Dichotomy • Effects of genes involve environmental processes • PKU and phenylalanine • genes influence smoking behaviour (through variations in addictive response) and the smoke exposure leads to lung cancer i.e. environmental mediation of genetic effects • genes determine ‘race’ but implications in terms of most racial inequalities largely depend on social processes

17. A False Dichotomy • Gene by Environment Interaction • genes code for biochemical processes quite distal to the outcomes of interest - there are many intermediate stages at which the environment and the social will modulate that effect • early puberty and poor educational outcomes among girls (Pickles, Magnusson, Cairns etc)

18. Rate of Depression by 5-HTTPR Genotype and Life-Events(847 26-year-olds from Dunedin study:Caspi, Mofitt et al 2003, Science)

19. MAOA and Antisocial behaviour • Environmentally contingent expression • Dunedin Cohort Study (Caspi, Moffitt et al. 2002 Science) In the absence of parenting adversity those boys with the genotype for low MAOA activity had no higher rate of violent crime but those who had experienced parenting adversity had 4 times the rate of violent crime

20. Twin Analysis of Two Measures Y & Z MZ=1,DZ=0.5 E A C C A E Z2 Y1 Z1 Y2 E A C C A E

21. Multivariate Twin Models • Use of cross-twin cross-measure information • The correlation of Twin 1’s hyperactivity with Twin 2 ‘s conduct disorder is higher for MZ’s than for DZ’s. • the genes that predispose to hyperactivity also predispose to conduct disorder (Silberg et al 1996)

22. Twin Analysis of Repeated Measures:response to stress Combining natural experiments and constructed experiments: Twins on exercise bikes. • Heart rate at rest substantially ‘genetic’ • Heart rate under stress somewhat more ‘genetic’ • Heart rate under stress related to substantially different genes to heart rate at rest • Are the effects of these genes purely biological? • While some may be ‘God-given constitution’ others will reflect much longer term processes e.g. genes that predispose to enjoying exercise and thus being ‘fit, genes that predispose to obesity and vascular deterioration etc • These are effects that can be moderated by social policy

23. Genetics of Language Development (SLI Consortium) • Expressive language development heritable (twin studies and molecular linkage studies) • Linkage results for children in middle-childhood show: - Strong linkage to non-word repetition task (Chr 16) - Strong linkage to expressive language (CELF) (Chr 19) - limitations in word acquisition (with genes on Chr16) may constrain early speech development but by middle childhood it is not vocabulary but (say) grammatical complexity that may be constraining (with genes on Chr 19)

24. What is the effect of a gene? Depends on who you are (other genes and proximal social factors) • Depends where you are (social context) • Depends on your developmental stage • Depends on what has happened to you in the past

25. Genetic Research Designs • In principle genetic designs offer researchers interested in social processes opportunities for ’control’ as great as those offered by longitudinal studies

26. MZ (Identical) co-twin controls • In longitudinal studies we might control for omitted variables by examining how change in outcome (difference between time 1 and time 2) is associated with change in environmental exposure • MZ differences in outcome can be similarly compared with differences in exposure

27. Adoptee Designs • Differences in outcome means and outcome-exposure correlations for children • Maughan et al. found substantial improved outcomes for adoptees and, at least for girls, that parental interest in education was a strong predictor of education attainment

28. Gene by Environment Correlation • Passive GrE • home environment and educational attainment • Active GrE • choosing an antisocial peer-group/gang • Reactive or evocative GrE • antisocial children provoking negative responses

29. Evocative GrE correlationsColarado adoption study O’Connor et al. 1998 Age 7 Age 9 Age 10 Negative parenting Negative parenting Negative parenting Genetic risk from bio-mum Child behaviour Child behaviour Child behaviour

30. Genetics and the Life-course • Barkers fetal programming may merely represent heterotypic continuity of a common set of genes • Genes for acquiring health capital (peak bone mass) protect into old age (osteoporosis)

31. Genetics and the Life-course • Overall percent genetic variance generally uninteresting but identifying which steps along a chain are more or less susceptible to environmental manipulation may be helpful

32. Variance, averages, propensities and targetting • Geographical variation not due to genes • Means, variances and thresholds • a high prevalence can be due to a high mean or high variance • for social outcomes genes largely contribute to variance • Universal or targetted policy • targetting by propensity, by phenotype, by family or by area

33. Conclusions • For social and many health outcomes effects of genes are socially mediated - that the genetic advantage/disadvantage of some may be persistent and unresponsive to typical policy does not refute this. • Genetic designs provide another tool for unravelling social processes • We need sociologically informed genetics and genetically informed sociology