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Overlapping genetic association in type I and type II diabetes

Due to the potential shared aetiology between type I and type II diabetes, researchers recently aimed to identify any genetic regions associated between both diseases.

Diabetes

There is a genetic component to both type I and type II diabetes. Examining these regions could potentially uncover signals that simultaneously alter disease risk for both diseases (colocalisation). As a result, this could provide biological insights into shared disease mechanisms. This in turn could potentially reveal effective therapeutic targets for both diseases.

A recent study suggested that the same variant is altering risk of both diseases in five regions. This included near Centromere Protein W (CENPW), Chymotripsinogen B1 (CTRB1)/Breast Cancer Anti-Oestrogen Resistance Protein 1 (BCAR1), GLIS Family Zinc Finger Protein (GLIS3), B-cell Lymphoma 11A (BCL11A) and Thyroid Adenoma-Associated Protein (THADA).

Genetic analysis

In a study, published as preprint in bioRxiv, researchers used publicly available summary statistics from GWAS meta-analyses to identify colocalising regions. Specifically, they obtained summary statistics from a type I meta-analysis on individuals from UK and Sardinia (7,467 cases and 10,218 controls) and a type II meta-analysis from individuals of European ancestry (74,124 cases and 824,006 controls). The team identified all regions of 0.5 Mb that contained variants associated with both diseases.

They found 81 association signals from 42 genetic regions that associated with both type I and type II diabetes. Of these, four association signals colocalised between both diseases. These included:

  • Chromosome 16q23.1, near CTRB1/BCAR1 (which has been previously identified)
  • Chromosome 11p15.5, near the Insulin (INS) gene
  • Chromosome 4p16.3, near Transmembrane protein 129 (TMEM129)
  • Chromosome 1p31.3, near Phosphoglucomutase 1 (PGM1)

Interestingly, they found that in each of these regions, the effects of the variant on type I diabetes were in the opposite direction to the effect on type II. This effect suggests a complex genetic relationship between the two diseases.

Using additional datasets, the team also supported the previously identified colocalisation on chromosome 9p24.2, near the GLIS3 gene. In this case, the direction of effect was concordant.

The team noted that larger sample sizes are needed to identify the depth of genetically identified therapeutic targets to treat or prevent both diseases.

Image credit: By xb100 – www.freepik.com


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Diabetes / Genetic Variants