Genetic Screening for Susceptibility to Disease


Claims of current and future benefits from genetic susceptibility screening are misleading because genetic variants are poor predictors of most diseases in most people and biology is complex. To date, the single and combined effects of common genetic variants on disease risk do not meet medical screening criteria for the general population.

Nevertheless, numerous commercial companies are attempting to establish a market in such tests, often combined with the personalized marketing of associated products or services. Significant political and financial commitments have been made to implementing genetic susceptibility screening in whole populations. These commitments reflect the historical promotion of genetic ‘prediction and prevention’ of disease by vested interests, and rest on a number of implausible biological assumptions. An independent assessment of the likely costs and benefits of this health strategy is long overdue. Regulation of the clinical validity and utility of genetic susceptibility tests is also needed.

Key concepts

  • Strategies for preventive health are influenced by commercial and political considerations.

  • The single or combined effects of common genetic variants on disease risk do not meet medical screening criteria for the general population.

  • Claims of future improvements in prediction depend on oversimplified models and implausible assumptions.

  • Heritability calculations assume that the effects of interactions, chance, society and choice on the variance of a trait are negligible or nonexistent.

  • There are always limits to the predictability of complex systems, particularly when the underlying physics or biology is poorly understood.

  • It is normal for highly parameterized models to give poor predictions.

  • Data‐mining tends to lead to well‐calibrated models with little or no predictive value.

  • Successful personalized marketing is not the same as delivering benefits to health.

  • The lack of a premarket assessment of clinical validity and utility means that most genetic susceptibility tests currently on sale are misleading to consumers.

Keywords: polygenic; susceptibility; screening; heritability; prediction


Beven KJ (2006) A manifesto for the equifinality thesis. Journal of Hydrology 320(1–2): 8–36.

Bolnick DA, Fulwilley D, Duster T et al. (2007) The science and business of genetic ancestry testing. Science 318: 399–400.

Buchanan AV, Sholtis S, Richtsmeier J and Weiss KM (2009) What are genes “for” or where are traits “from”? What is the question? BioEssays 31: 198–208.

Carter JN, Ballester PJ, Tavassoli Z and King PR (2006) Our calibrated model has no predictive value: an example from the petroleum industry. Reliability Engineering & System Safety 91(10–11): 1373–1381.

Collins FS (1999) Shattuck lecture – medical and societal consequences of the Human Genome Project. New England Journal of Medicine 341: 28–37.

Council of Europe (2008) Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Genetic Testing for Health Purposes. Brussels, Belgium. Available at

Dyson F (2004) A meeting with Enrico Fermi. Nature 427: 297.

Eddington AS (1957) The decline of determinism. In: Gardner M (ed.) Great Essays in Science. New York: Pocket Books.

Elliot R and Ong TJ (2002) Nutritional genomics. British Medical Journal 321: 1438–1441.

Fisher RA (1918) The correlation between relatives on the supposition of Mendelian inheritance. Transactions of the Royal Society of Edinburgh 52: 399–433.

Fleming N (2008) Rival genetic tests leave buyers confused. The Sunday Times, 7 September.

Frayling TM, Timpson NJ, Weedon MN et al. (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316(5826): 889–894.

Gartner CE, Barendregt JJ and Hall WD (2009) Multiple genetic tests for susceptibility to smoking do not outperform simple family history. Addiction 104: 118–126.

Gilham I and Rowland T (2001) Predictive medicine: potential benefits from the integration of diagnostics and pharmaceuticals. International Journal of Medical Marketing 2: 18–22.

Guo S‐W (2000) Gene‐environment interaction and the mapping of complex traits: some statistical models and their interpretation. Human Heredity 50: 286–303.

Henderson M (2009) Genetic mapping of babies by 2019 will transform preventive medicine. The Times. 9 February.

Hogarth S, Javitt G and Melzer D (2008) The current landscape for direct‐to‐consumer genetic testing: legal, ethical, and policy issues. Annual Review of Genomics and Human Genetics 9: 161–182.

Hopper JL (2000) Why ‘common environmental effects’ are so uncommon in the literature. In: Spector TD, Sneider H and MacGregor AJ (eds) Advances in Twin and Sib‐Pair Analysis. London: Greenwich Medical Media Ltd.

Jakobsdottir J, Gorin MB, Conley YP, Ferrell RE and Weeks DE (2009) Interpretation of genetic association studies: markers with replicated highly significant odds ratios may be poor classifiers. PLoS Genetics 5(2): e1000337.

Janssens ACJW and van Duijn CM (2008) Genome‐based prediction of common diseases: advances and prospects. Human Molecular Genetics 17(R2): R166–R173.

Janssens ACJW, Gwinn M, Bradley LA et al. (2008) A critical appraisal of the scientific basis of commercial genomic profiles used to assess health risks and personalize health interventions. The American Journal of Human Genetics 82: 593–599.‐6.

Jonas J and Harper J (2006) Effective counterterrorism and the limited role of predictive data mining. Policy Analysis, 584. Cato Institute, 11 December.

Kevles DJ (1995) In the name of eugenics. Cambridge, MA: Harvard University Press.

Khoury MJ and Wagener DK (1995) Epidemiological evaluation of the use of genetics to improve the predictive value of disease risk factors. American Journal of Human Genetics 56: 835–844.

Kraft P (2008) Curses – winner's and otherwise – in genetic epidemiology. Epidemiology 19(5): 649–651.

Layzer D (1974) Heritability analyses of IQ scores: science or numerology? Science 183: 1259–1266.

Lee SH, van der Werf JHJ, Hayes BJ, Goddard ME and Visscher PM (2008) Predicting unobserved phenotypes for complex traits from whole‐genome SNP data. PloS Genetics 4(1): e1000231.

Lehoux P, Williams‐Jones B, Miller F, Urbach D and Tailliez S (2008) What leads to better health care innovation? Arguments for an integrated policy‐orientated research agenda. Journal of Health Services Research and Policy 13(4): 251–254.

Lewis SJ and Brunner EJ (2004) Methodological problems in genetic association studies of longevity – the apolipoprotein E gene as an example. International Journal of Epidemiology 33: 962–970.

Liu W, Zhao W and Chase GA (2004) Genome scan meta‐analysis for hypertension. American Journal of Hypertension 17: 1100–1106.

Maher B (2008) The case of the missing heritability. Nature 456(6): 18–21.

Meigs JB, Shrader P, Sullivan LM et al. (2008) Genotype score in addition to common risk factors for prediction of Type 2 Diabetes. New England Journal of Medicine 359: 2208–2219.

Munafò MR (2009) The clinical utility of genetic tests. Addiction 104: 127–128.

Porteous JW (2004) A rational treatment of Mendelian genetics. Theoretical Biology and Medical Modelling 1(6) DOI: 10.1186/1742‐4682‐1‐6.

Reuters (1958) Genetic basis suggested. The New York Times, 13 July. Bates No. 10030982/0982. Council for Tobacco Research. Available at

Risch N (1990) Linkage strategies for genetically complex traits. I. Multilocus models. American Journal of Human Genetics 46: 222–228.

Rose G (1985) Sick individuals and sick populations. International Journal of Epidemiology 14(1): 32–38.

Rose H (1994) Love, power and knowledge. Cambridge: Polity Press.

Rose SPR (2006) Heritability estimates – long past their sell‐by date. International Journal of Epidemiology 35: 525–527

Sabatti C, Service SK, Hartikainen A‐L et al. (2009) Genome‐wide association analysis of metabolic traits in a birth cohort from a founder population. Nature Genetics 41(1): 35–701.

SACGHS (2008) US system of oversight of genetic testing: a response to the charge of the Secretary of Health and Human Services. Report of the Secretary's Advisory Committee on Genetics, Health and Society, April.

Sarkar S (1998) Genetics and reductionism. Cambridge, UK: Cambridge University Press.

Slatkin M (2008a) Exchangeable models of complex inherited diseases. Genetics 179: 2253–2261.

Slatkin M (2008b) Genotype‐specific recurrence risks and indicators of the genetic architecture of complex diseases. The American Journal of Human Genetics 83: 120–126.

Sykes R (2000) New medicines, the practice of medicine, and public policy. Nuffield Trust. The Stationary Office, London.

Taioli E and Garte S (2002) Covariates and confounding in epidemiologic studies using metabolic gene polymorphisms. International Journal of Cancer 100: 97–100.

Terwilliger JD and Weiss KM (2003) Confounding, ascertainment bias, and the blind quest for a genetic ‘fountain of youth’. Annals of Medicine 35: 532–544.

Tryggvadottir L, Sigvaldason H, Olafsdottir GH et al. (2006) Population‐based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920–2000. Journal of the National Cancer Institute 92(2): 116–122.

Walker W (1999) Nuclear entrapment: THORP and the politics of commitment. London: IPPR.

Wallace HM (forthcoming) Big Tobacco and the human genome: driving the scientific bandwagon? Genomics, Society and Policy.

Wallace HM (2006) A model of gene–gene and gene–environment interactions and its implications for targeting environmental interventions by genotype. Theoretical Biology and Medical Modelling 3(35): doi: 10.1186/1742‐4682‐3‐35.

Wallace HM (2008a) 23 and Me: Enough to make you spit? [Poem]

Wallace HM (2008b) Most gene test sales are misleading. Nature Biotechnology 26(11): 1221.

Weiss KM (2008) Tilting at Quixotic Trait Loci (QTL): an evolutionary perspective on disease causation. Genetics 179: 1741–1756.

WHO (2008) Closing the gap in a generation. Commission on Social Determinants of Health.

Wray NR, Goddard ME and Visscher PM (2008) Prediction of individual risk of complex disease. Current Opinion in Genetics & Development 18: 257–263.

Wu X, Kumar V, Quinlan JR et al. (2008) Top 10 algorithms in data‐mining. Knowledge Information Systems 14: 1–37.

Further Reading

Fox Keller E (2000) The century of the gene. Cambridge, MA: Harvard University Press.

Lewontin RC (1991) The doctrine of DNA. London: Penguin.

Moss L (2003) What genes can't do. Cambridge, MA: MIT Press.

Proctor RN (1995) Cancer wars: How politics shapes what we know and don't know about cancer. New York: Basic Books.

Rose G (1992) The strategy of preventive medicine. Oxford: Oxford University Press.

Wallace HM (2006) Your diet tailored to your genes: Preventing diseases or misleading marketing? GeneWatch, UK: Buxton. Available on:

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Wallace, Helen M(Sep 2009) Genetic Screening for Susceptibility to Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021790]