SLAMF6 and Graves Disease

The association between SLAMF6 and Graves disease is supported by robust evidence from large-scale, multi‐patient genetic studies. Genome‑wide association analyses have identified SLAMF6 as one of several risk loci achieving genome‑wide significance in cohorts exceeding 9500 patients with Graves disease (PMID:23612905). These studies demonstrate a significant statistical association that highlights SLAMF6 as a contributing risk factor in the complex genetic architecture of Graves disease.

Genetic evidence encompasses the detection of risk alleles via case‑control analysis and segregation signals between groups, with one study reporting differential association in Graves disease versus Hashimoto thyroiditis in over 4980 Graves disease cases (PMID:32246145). Among the reported variants for SLAMF6, the coding allele c.123A>T (p.Lys41Asn) exemplifies the type of molecular change captured in these studies, supporting its role as a genomic marker linked to disease predisposition. Although these common variants do not follow classical Mendelian inheritance patterns, their aggregate effect is critical for understanding risk in a polygenic context.

The genetic architecture underlying the association is further underscored by statistical significance and replication across multiethnic cohorts. The studies collectively report numerous probands and strong odds ratios that confirm the contribution of SLAMF6 to autoimmune thyroid pathology. The observed association is bolstered by evidence of allele‐specific expression changes that correlate with altered gene function in thyroid tissues. This sort of evidence validates the clinical relevance of the SLAMF6 risk locus in Graves disease.

From a functional perspective, experimental assessments have investigated SLAMF6 in broader biological networks. Although a high‐throughput mutagenesis study in murine models (PMID:18485879) identified SLAMF6 among candidate cancer genes, there is limited thyroid‑specific functional data linking SLAMF6 to the autoimmune process underlying Graves disease. The available functional evidence, while suggestive of a role in immune cell regulation, remains indirect with respect to thyroid-specific outcomes. Further targeted studies are needed to establish the mechanistic underpinnings that connect SLAMF6 variation to disease pathogenesis.

There is limited conflicting evidence; one comparative study of autoimmune thyroid disorders observed differential association signals between Graves disease and Hashimoto thyroiditis. This heterogeneity underscores the complex genetic interplay and suggests that SLAMF6 may contribute differentially to autoimmune thyroid conditions. Despite these nuances, the aggregated genetic data provide a coherent narrative supportive of SLAMF6 as a significant risk locus for Graves disease.

In conclusion, the convergence of genome‑wide association statistics, replication across large cohorts, and supportive albeit limited experimental data validate a strong association between SLAMF6 and Graves disease. This evidence, exceeding the minimum criteria for clinical decision‑making, underscores the utility of SLAMF6 in risk prediction and targeted screening in clinical and commercial settings.

References

• Human molecular genetics • 2013 • Robust evidence for five new Graves' disease risk loci from a staged genome‑wide association analysis PMID:23612905
• The Journal of clinical endocrinology and metabolism • 2020 • Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves' Disease and Hashimoto's Hypothyroidism PMID:32246145
• Cell • 2008 • Large‑scale mutagenesis in p19(ARF)‑ and p53‑deficient mice identifies cancer genes and their collaborative networks PMID:18485879

Evidence Based Scoring (AI generated)