Thwart your destiny; effect of NAFLD genes on steatosis, liver injury and cirrhosis varies by body mass index
Abstract
Most common human diseases develop because of a combination of endogenous risk combined with exposures. Said another way, these diseases are attributed to genetic risk combined with environmental triggers. Nonalcoholic fatty liver disease (NAFLD) is no exception. There have been both genetic and environmental variables that have been associated with NAFLD. One recent article, however, goes beyond these associations to understand how environmental exposures in the setting of genetic risk variants can exacerbate the development of NAFLD. Genetic associations studies usually assume an additive genetic model to assess for association with disease. This translates to a model where having 0, 1, or 2 alleles of a genetic variant increases the risk of the disease linearly. However, there are situations where those same alleles instead of increasing risk additively increase risk multiplicatively. That is, having 0, 1, or 2 alleles increases risk under one set of conditions (body mass index [BMI] 35 kg/m) from 1 to 8 to 16 (Fig. 1A). The condition under which the effects of the same genotype changes is called a modifier. Identifying environmental modifiers of genetic risk can be done by looking for gene environment interactions. It is important to identify modifiers of disease because if the modifier can be changed, the increased genetic risk for development of disease can be preferentially and dramatically mitigated. A recent article by Stender et al. examined the effect of adiposity…
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Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.
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