AIG1 – Osteoarthritis

This summary evaluates the association between the AIG1 gene (HGNC:21607) and osteoarthritis (MONDO:0005178). The evidence comes from a large-scale study that integrated polygenic risk scores to assess osteoarthritis risk in a cohort of adults over 40 years (PMID:35204431). Although osteoarthritis is a complex condition with multiple genetic factors, the variant in AIG1 has been implicated as one contributor among several in the polygenic risk model.

In assessing clinical validity, the overall strength of the association is considered Limited. This categorization is based on a single multi-patient study involving 580 cases (PMID:35204431), which lacks independent segregation data and does not present a clearly defined causal coding variant in AIG1. The association is derived from statistical models rather than from robust familial or mechanistic data.

The genetic evidence supporting the association is also Limited. Although the best five-SNP model from the study included an AIG1 variant (AIG1_rs6570550), no corresponding complete HGVS coding change meeting the required format (starting with “c.” and including a three-letter amino acid notation) was provided in the evidence. Consequently, while AIG1 is a component of the polygenic risk score, its individual contribution remains modest and less defined.

Regarding functional evidence, there is a lack of direct experimental or functional assessment data for AIG1 in the context of osteoarthritis. No in vitro or in vivo studies have demonstrated that perturbations in AIG1 function result in osteoarthritic phenotypes, thereby limiting the evidence for a causative mechanism.

The findings from the study suggest that the polygenic risk score—including the AIG1 component—is associated with increased osteoarthritis risk, particularly in dietary contexts where energy, protein, fat, and alcohol intake interact with genetic background (PMID:35204431). Although additional evidence may exist from other factors contributing to osteoarthritis, the data specific to AIG1 do not yet reach a level to support a definitive causal role.

Key take‑home: Variants in AIG1 may represent a contributory risk factor for osteoarthritis, reinforcing the need for further studies to explore its mechanistic role and potential utility in personalized nutritional interventions for osteoarthritis risk reduction.

References

• Diagnostics (Basel, Switzerland) • 2022 • Polygenetic Variants Related to Osteoarthritis Risk and Their Interactions with Energy, Protein, Fat, and Alcohol Intake in Adults in a Large Cohort PMID:35204431

Evidence Based Scoring (AI generated)