Genome-based prediction of common diseases: advances and prospects

Abstract

Common diseases such as type 2 diabetes and coronary heart disease result from a complex interplay of genetic and environmental factors. Recent developments in genomics research have boosted progress in the discovery of susceptibility genes and fueled expectations about opportunities of genetic profiling for personalizing medicine. Personalized medicine requires a test that fairly accurately predicts disease risk, particularly when interventions are invasive, expensive or have major side effects. Recent studies on the prediction of common diseases based on multiple genetic variants alone or in addition to traditional disease risk factors showed limited predictive value so far, but all have investigated only a limited number of susceptibility variants. New gene discoveries from genome-wide association studies will certainly further improve the prediction of common diseases, but the question is whether this improvement is sufficient to enable personalized medicine. In this paper, we argue that new gene discoveries may not evidently improve the prediction of common diseases to a degree that it will change the management of individuals at increased risk. Substantial improvements may only be expected if we manage to understand the complete causal mechanisms of common diseases to a similar extent as we understand those of monogenic disorders. Genomics research will contribute to this understanding, but it is likely that the complexity of complex diseases may ultimately limit the opportunities for accurate prediction of disease in asymptomatic individuals as unraveling their complete causal pathways may be impossible.

Gene–gene interactions contribute to eye colour variation in humans

“…4 Prediction of phenotypes from genetic data is considered to be important in both medical and forensic examinations. In particular, it can improve medical care by more accurate prognosis and prevention 5,6 and speed up forensic investigations by providing information concerning externally visible traits in criminal non-suspect cases or cases concerning identification of human remains. 7,8 Variation in pigmentation phenotype is particularly high in humans, especially in populations of European descent, and thus prediction of this phenotype would seem to provide information of particular importance for forensic examinations.…”

Points to consider in assessing and appraising predictive genetic tests

“…Instead, gene-environment interaction appears to play an important role, and genetic tests should undergo the same analysis of predictive power as phenotype-based tests. In most cases, a brief look at a patient's body weight as well as a brief family history of disease may tell a doctor much more about his or her risk for diabetes or myocardial infarction than a predictive genetic test (van der Net et al 2009;van Hoek et al 2008;Janssens and van Duijn 2008). Consequently, the additional value of predictive genetic testing may be quite limited, even if the genotype is significantly associated with the risk of the disease outcome.…”

Biomarker discovery, high performance and cloud computing: A comprehensive review

“…Biomarkers have improved identification, treatment and prevention of complex common diseases including cancer, diabetes and cardiovascular disease [4]. Moreover, they have been applied to identify diseases such as alzheimer's [5], breast cancer [6] and kidney disease [7] playing a central role in the identification of novel targeted and effective therapeutics.…”