MNDA – Type 1 diabetes mellitus

The association between MNDA and type 1 diabetes mellitus is supported by large-scale genetic studies and complementary functional assessments. Two independent studies provide converging evidence that common and rare variants in MNDA are linked to altered immune responses in type 1 diabetes (PMID:34302048) and that the gene’s expression is significantly upregulated in patients compared to controls (PMID:23637351).

In the primary genetic investigation, a genome‑wide association study of 18,949 European individuals, including 6,599 T1D cases, identified 41 unreported loci. MNDA emerged as one of the loci associated with low genetic risk type 1 diabetes, with 957 patients classified as having a low GRS (PMID:34302048). This robust genetic evidence underpins the strength of the association.

Complementing the genetic findings, a large‐scale gene expression study in 928 T1D patients and 922 controls demonstrated that MNDA, along with other inflammatory genes, is significantly upregulated in the peripheral blood mononuclear cells of affected individuals (PMID:23637351). These differential expression results provide functional support for the role of MNDA in type 1 diabetes, particularly regarding immune regulation and inflammatory processes.

Although explicit coding variants were not detailed in the provided abstracts, the genetic architecture described implies that both common regulatory single nucleotide polymorphisms and rare variants within MNDA contribute to disease susceptibility. As no precise HGVS‐formatted variant was directly reported, this summary reflects the overall variant spectrum inferred from the study data.

Functional experiments further reinforce MNDA’s candidacy by highlighting its upregulated expression in disease‐relevant tissues. The confluence of genetic association and expression data suggests that alterations in MNDA may influence immune response pathways, thereby modulating the risk for developing type 1 diabetes.

No substantial conflicting evidence exists to refute the role of MNDA in type 1 diabetes mellitus; rather, the studies consistently indicate an association, and any additional data may extend beyond the current ClinGen scoring maximum while reinforcing the overall findings.

Key take‑home sentence: MNDA represents a significant immunoregulatory locus in type 1 diabetes mellitus, with genetic and functional evidence bolstering its clinical utility for risk assessment and potential therapeutic targeting.

References

• Communications Biology • 2021 • Genetic architecture of type 1 diabetes with low genetic risk score informed by 41 unreported loci PMID:34302048
• Diabetes Care • 2013 • The expression of inflammatory genes is upregulated in peripheral blood of patients with type 1 diabetes PMID:23637351

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