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Type 1 diabetes (T1D) is a complex autoimmune disease characterised by an absolute deficiency of insulin. It affects more than 20 million people worldwide and imposes an enormous financial burden on patients. The underlying pathogenic mechanisms of T1D are still obscure, but it is widely accepted that genetics and the environment play an essential role in its onset and development. Many hypotheses have been proposed to explain the missing heritability, including variants remaining to be found (variants with small effect sizes, rare variants and structural variants) and interactions (gene–gene and gene–environment interactions; e.g. epigenetic effects). In the following review, the study introduces the possible sources of missing heritability and discusses the related knowledge in the context of T1D.
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