The threshold hypothesis: solving the equation of nurture vs nature in type 1 diabetes

Abstract

For more than 40 years, the contributions of nurture (i.e. the environment) and nature (i.e. genetics) have been touted for their aetiological importance in type 1 diabetes. Disappointingly, knowledge gains in these areas, while individually successful, have to a large extent occurred in isolation from each other. One reason underlying this divide is the lack of a testable model that simultaneously considers the contributions of genetic and environmental determinants in the formation of this and potentially other disorders that are subject to these variables. To address this void, we have designed a model based on the hypothesis that the aetiological influences of genetics and environment, when evaluated as intersecting and reciprocal trend lines based on odds ratios, result in a method of concurrently evaluating both facets and defining the attributable risk of clinical onset of type 1 diabetes. The model, which we have elected to term the 'threshold hypothesis', also provides a novel means of conceptualising the complex interactions of nurture with nature in type 1 diabetes across various geographical populations.

Fig. 1

The traditional model describing the relationship and interplay between genetics and environment in type 1 diabetes

Fig. 2

A novel, hypothetical model designed to describe the complex nature and interactions between genes and environment in type 1 diabetes. VNTR, variable number tandem repeat