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

• Published in: Diabetologia Vol. 54; no. 9; pp. 2232 - 2236
• Main Authors: Wasserfall, C., Nead, K., Mathews, C., Atkinson, M. A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.09.2011; Springer; Springer Nature B.V
• Subjects: Age Factors; Biological and medical sciences; Diabetes; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Environment; Etiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; For Debate; Genetic Predisposition to Disease - etiology; Genetic Predisposition to Disease - genetics; Genetics; Health risk assessment; Human Physiology; Humans; Hypotheses; Immune system; Incidence; Insulin; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Models, Biological; Risk Factors; Immunology; Aetiopathogenesis; Type 1 diabetes; Disease modelling; Environment; Genetics; Viruses; Endocrinopathy; Immunopathology; Autoimmune disease
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-011-2244-z

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.