IJE vol.33 no.5 © International Epidemiological Association 2004; all rights reserved.
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Genetic epidemiology: an ‘enlightened narrative’?
Genetic epidemiology—the theme of this issue of the International Journal of Epidemiology—has been viewed as almost the antithesis of behavioural, environmental, or social epidemiology. This line of reasoning sees genetic epidemiology as primarily investigating nonmodifiable biological factors, which must lead to a purely biological notion of disease causation, prevention, and treatment.1 This critique can be expanded to cover two features of findings from genetic association studies: that the population-attributable risk of the genetic variants is low and that in any case the influence of genetic factors is not reversible. Illustrating both of these criticisms, Terwilliger and Weiss2 suggest, as reasons for considering that many of the current claims regarding genetic epidemiology are hype, first, that alleles identified as increasing the risk of common diseases ‘tend to be involved in only a small subset of all cases of such diseases’ and, second, that in any case ‘while the concept of attributable risk is an important one for evaluating the impact of removable environmental factors, for non-removable genetic risk factors, it is a moot point’.
Social scientists have identified a ‘narrative of enlightened geneticization’3 through which researchers present an apparently reasonable and nonextremist view of disease causation that clearly accepts a role for nongenetic factors. However, this narrative ultimately prioritizes genetic explanations, subtly undermining the role of environmental influences. As epidemiologists with a public health perspective we surely want to resist this mode of discourse and produce work that has relevance for improving population health. Thus Paulo Vineis4 points out how standard methodologies in genetic epidemiology lead to an underestimation of the role of the environment in research aimed at examining gene–environment interaction. One form of reasoning, touched on by several of the contributors including Vineis,4 Khoury et al.,5 and Palmer,6 puts the environmental factors centre-stage by explicitly utilizing studies in which genetic variant–disease outcome associations can provide robust evidence regarding the causal nature of environmental factors influencing health.7–14 This approach intends to inform behavioural, environmental, or social approaches to disease control by helping to establish those causal factors for which intervention will influence disease rates. The approach does not inform strategies for genetic screening for disease risk or targeting of therapy. In this light the criticisms of Terwilliger and Weiss regarding the small subset of diseases that can be said to be ‘caused’ by the genetic variants, and the low population-attributable risk for the genetic variants, do not apply.
In the current issue of the International Journal of Epidemiology, for example, McKeown-Eyssen et al.15 explore genetic variant associations with multiple chemical sensitivity, a syndrome of for which the basis has been contested. Is it influenced by environmental exposures, or is it essentially a psychiatric condition? Associations between genetic variants that would be involved in detoxification of environmental agents and the syndrome provide some evidence of its basis in environmental exposures since there is little reason to believe that these variants influence psychiatric state. A similar approach has been taken by Cherry and colleagues with respect to the medical consequences of sheep dip exposure,16 through identification of an association between symptom reporting and a genetic variant related to impaired detoxification of organophosphates, which are present in sheep dip and could cause these symptoms. If psychological factors or a desire to obtain compensation generated the syndrome, it is unlikely that such associations would be found. Both studies require replication in larger sample sizes, however, since effect sizes are generally small for genetic variant–disease associations and many misidentifications have occurred.17 Keavney and colleagues18 demonstrate another potential problem with this approach when they show that some genotypes related to adverse blood lipid concentrations are not associated with the elevated risks of coronary heart disease that would be predicted by the lipid differences. Their discussion demonstrates the need to have considerable understanding of the function of genetic variants to make robust interpretations, as Vineis4 and Khoury et al.5 discuss.
Much contemporary genetic epidemiology—as illustrated by the articles by Keavney et al.,18 McKeown-Eyssen et al.,15 Morita et al.,19 Morrison,20 Sparks et al.,21 and Lewis and Brunner22 in this issue—is concerned with relating genetic variants to disease outcomes. However, as Jablonka elegantly demonstrates, there are other exciting possibilities that have arisen with the increased ability to study epigenetic inheritance systems.23 Iliadou and colleagues24 extend the classic twin studies method to provide more robust evidence on whether birthweight and fetal growth are related to type 2 diabetes, providing evidence that nongenetic contributions to fetal growth are indeed of importance, although the interpretation is not unambiguous, as both the authors and Phillips25 discuss. The interpretation of twin studies of birthweight and blood pressure is more problematic, as McNeill and colleagues show in their meta-analysis of this issue.26
The importance of the environment for health is discussed in other articles in this issue. At the international level this is covered by Pearce and others in the symposium on globalization and health.27–30 Other environmental factors receiving attention include ionizing radiation and cancer,31 smoking in China,32 violence in Iceland,33 air conditioning in France,34 parasite infections in the Côte d'Ivoire,35 unintentional drowning in Finland,36 Hepatitis C virus infection and non-Hodgkin's lymphoma in Egypt,37 and lifetime socioeconomic circumstances in Britain.38 All in all, there should be enough in this issue to keep Anne Stevenson's apothecary happy.39
References
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2 Terwilliger JD, Weiss WM. Confounding, ascertainment bias, and the blind quest for a genetic ‘fountain of youth’. Ann Med 2003; 35:532–44.[CrossRef][ISI][Medline]
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4 Vineis P. A self-fulfilling prophecy: are we underestimating the role of the environment in gene–environment interaction research? Int J Epidemiol 2004; 33:945–46.
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19 Morita A, Masayuki I, Dohi Y et al. Vitamin D receptor polymorphisms are not good predictors of the bone mineral density in representative samples of Japanese women. Int J Epidemiol 2004; 33:979–88.
20 Morrison N. Commentary: Vitamin D receptor polymorphism and bone mineral density; effect size in Caucasians means detection is uncertain in small studies. Int J Epidemiol 2004; 33:989–94.
21 Sparks R, Bigler J, Sibert JG, Potter JD, Yasui Y, Ulrich CM. TGFß1 polymorphism (L10P) and risk of colorectal adenomatous and hyperplastic polyps. Int J Epidemiol 2004; 33:955–61.
22 Lewis SJ, Brunner EJ. Methodological issues in genetic association studies of longevity—the apolipoprotein E gene as an example? Int J Epidemiol 2004; 33:962–70.
23 Jablonka E. Epigenetic epidemiology. Int J Epidemiol 2004; 33:929–35.
24 Iliadou A, Cnattingius S, Lichtenstein P. Low birthweight and type 2 diabetes: a study on 11162 Swedish twins. Int J Epidemiol 2004; 33: 948–53.
25 Phillips D. Commentary: Twins, low birthweight and type 2 diabetes. Int J Epidemiol 2004; 33:953–54.
26 McNeill G, Tuya C, Smith WCS. The role of genetic and environmental factors in the association between birthweight and blood pressure: evidence from meta-analysis of twin studies. Int J Epidemiol 2004; 33:995–1001.
27 Pearce N. The globalization of epidemiology: introductory remarks. Int J Epidemiol 2004; 33:1127–31.
28 Durie M. Understanding health and illness: research at the interface between science and indigenous knowledge. Int J Epidemiol 2004; 33:1138–43.
29 Barreto ML. The globalization of epidemiology: critical thoughts from Latin America. Int J Epidemiol 2004; 33:1132–37.
30 Loewenson R. Epidemiology in the era of globalization: skills transfer or new skills? Int J Epidemiol 2004; 33:1144–50.
31 Mahoney MC, Lawvere S, Falkner KL et al. Thyroid cancer incidence trends in Belarus: examining the impact of Chernobyl. Int J Epidemiol 2004; 33:1025–33.
32 Yang G, Ma J, Chen AP, Brown S, Taylor CE, Samet JM. Smoking among adolescents in China: 1998 survey findings. Int J Epidemiol 2004; 33:1103–10.
33 Gudlaugsdottir GR, Vilhjalmsson, Kristjansdottir, Jacobsen R, Meyrowitsch D. Violent behaviour among adolescents in Iceland: a national survey. Int J Epidemiol 2004; 33:1046–51.
34 Preziosi P, Czernichow S, Gehanno P, Hercberg S. Workplace air-conditioning and health services attendance among French middle-aged women: a prospective cohort study. Int J Epidemiol 2004; 33:1120–23.
35 Raso G, Luginbühl A, Adjoua CA et al. Multiple parasite infections and their relationship to self-reported morbidity in a community of rural Côte d'Ivoire. Int J Epidemiol 2004; 33:1092–1102.
36 Lunetta. Unintentional drowning in Finland 1970–2000. Int J Epidemiol 2004; 33:1053–63.
37 Cowgill KD, Loffredo CA, Eissa SA-L et al. A case–control study on non-Hodgkin's lymphoma and hepatitis C virus infection in Egypt. Int J Epidemiol 2004; 33:1034–39.
38 Singh-Manoux A, Ferrie JE, Chandola T, Marmot M. Socioeconomic trajectories across the lifecourse and health outcomes in late midlife. Int J Epidemiol 2004; 33:1065–71.
39 Stevenson A. A ballad for apothecaries. In Granny Scarecrow. Tarset, Northumberland Bloodaxe, 2000. (Reprinted Int J Epidemiol 2004; 33:947.)
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