Genetics and behaviour: do we have a choice? Dr Helen Wallace GeneWatch UK

Overview Why behavioural genetics is (mostly) wrong Important (possible) exceptions Is it (mostly) harmless? What should be done?

Two types of evidence Twin and family studies Genetic association studies

What do twin studies tell us? Twin and family data does not tell us how important genetic differences are in determining behaviour (but can show when genetic differences are not important). All measures of familial aggregation (including heritability) can be significant even in the absence of any genetic component of disease (Guo, 2000). If lots of different genes interact, genetic differences are (much) less important than if only one or two genes do. Analysis is deterministic (removes choice).

Genetic association studies are mostly wrong Hirschhorn et al (2002). Of 600 positive associations between common gene variants and disease, 166 had been studied 3 or more times and only 6 have been consistently replicated. Munafò et al (2003) combined 46 studies of common genetic variants and personality in health adults. Only one (5HTT LPR and avoidance) was statistically significant and this significance disappeared with a stricter test.

How do genes influence complex traits? Despite decades of research few genes have been found that play anything but a minor role in complex traits like heart disease, autism, schizophrenia or intelligence. The reason may be that such genes simply dont exist. Rather than being caused by single genes these traits may represent a network perturbation generated by small, almost imperceptible, changes in lots of genes. (Prof Johnjoe McFadden)

Gene-environment interactions One study (MAOA gene + maltreatment in childhood = antisocial behaviour). Major scientific dispute: is UK Biobank (500,000 people) big enough to estimate gene- environment interactions in disease? Targeting the genetically susceptible may not be a rational or acceptable way to ration resources. Most cases probably do not occur in high risk group. Those at high genetic risk may not have most to gain. People may not accept genetic rationing (Scott et al, 2005).

Population impacts of genetic personalisation

Important (possible) exceptions Most behaviours in most people are (extremely) unlikely to be predictable from their genes. There may be some exceptions if some behaviours are dominated by mutations in a single gene and/or involve relatively simple biological pathways (c.f. single-gene disorders). Examples of research: appetite and nicotine addiction.

Appetite A few (rare) genes are known where mutations cause uncontrollable appetite leading to obesity in childhood, e.g. the leptin (ob) gene. Of 200+ genes linked with common obesity, none are statistically significant. The food industry (ILSI) are funding research into functional foods to alter appetite and mood. The BioPsychology group at Leeds are researching genes which influence food choices. Are psycho foods the solution to obesity?

Nicotine addiction G-Nostics NicoTest. Nicotine addiction gene claim now removed from website. Pharmacogenetic claim (choosing Zyban or nicotine patches) continues (based on the first week of an 8 year study). University of Oxford has decided to transfer its shareholding back. Cancer Research Technology share [our] concerns and plans to have no ongoing involvement with G- Nostics. Lack of regulation and scientific diligence by investors.

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(Mostly) harmless? Some predictive genetic tests may be useful for some people, but market is unregulated. People should be able to take (rare) useful tests on medical grounds alone, without worrying about insurance/employment. Genetic research may help to understand mechanisms even if it cant quantify risk. But possible new products (such as anti-obesity drugs and psycho foods) also raise ethical issues. The myth that genes (plus environment) determine behaviour is itself dangerous...

Lessons for policy makers Most behavioural genetics is based on false assumptions: choice does exist (or IPPR would vanish in a puff of smoke). False solutions are costly (especially for diet and smoking). Most genetic information is genetic misinformation: genetic tests need regulation. Legislation to prevent genetic discrimination and protect privacy is also needed.