Trends in Molecular Medicine
Research FocusGenetic associations: false or true?
Section snippets
Empirical evidence, bias and heterogeneity
Lohmueller et al. have recently shown that these problems are not just theory [6]. In a large-scale empirical evaluation of 25 postulated genetic associations, they showed that the results of the first statistically significant (‘positive’) study were inflated when compared with the results of other published research on the same question. This is consistent with prior large-scale observations [7]. Omitting the first ‘positive’ study, is there still an association when only the remaining
A big picture of small effects
It is likely that most genuine genetic associations represent modest effects with odds ratios of 1.1–1.5 (i.e. a 10–50% relative increase in the likelihood of getting a disease). Any one polymorphism usually explains only 1–8% of the overall disease risk in the population. This might sound quite small, but the additive effect of several such risk factors could make up the 20–70% of the overall disease risk that is attributed to genetic factors in most common diseases. An adequately powered
Acknowledgements
J.P.A.I is also an Adjunct Professor of Medicine at the Division of Clinical Care Research, Department of Medicine, Tufts–New England Medical Center, Boston, MA, USA.
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