Genome-wide association studies may be misinterpreted: genes versus heritability

摘要

Much of the literature on genome-wide association studies (GWAS) is based on the premise that an important proportion of common diseases is heritable and that this proportion is likely to be due to genetic variants detectable with extensive scans of the DNA. Heritability is estimated from family studies, including twin studies and is based on the comparison of the variation in disease among different members of particular families. Since there is a wide gap between the population variation in disease explained by the results of GWAS (usually 50%), the question arises as to how to explain these differences. However, the premise for this question is based on two sources of misunderstanding: (i) confusion between variation and causation and (ii) confusion between heritability and genetic determination. As we show with a number of examples, variation is not causation and heritability is not genetic determination. Therefore, heritability studies do not provide valid estimates of the proportion of disease cases that are attributable to genetic factors. Such estimates in turn cannot be used to estimate the proportion of cases that are due to environmental factors.