INPP1 – Bipolar Disorder

The association between INPP1 (HGNC:6071) and bipolar disorder (MONDO_0004985) has been explored through both genetic screening and functional/epigenetic assessments. In a pharmacogenetics study (PMID:9682271), researchers identified four common coding region polymorphisms in INPP1. Notably, one missense variant, c.682A>G (p.Thr228Ala), was found and appeared enriched among lithium responders, suggesting its potential role in modulating treatment response.

Genetic evidence from this study indicates that although the variant spectrum in INPP1 includes several silent substitutions, the presence of the missense change in a subset of affected individuals provides a moderate level of support. However, detailed familial segregation data were not provided, limiting the ability to assess co-segregation; hence, no additional affected relatives were recorded (PMID:9682271).

A second study (PMID:38633806) investigated DNA methylation patterns at loci related to suicidal behavior in bipolar disorder and identified differential methylation at INPP1. This functional evidence supports a biological role for INPP1 in the phospholipase C signaling pathway, which is hypothesized to underpin the mood-stabilizing effects of lithium. Both studies, despite differences in methodology, contribute to a coherent narrative linking INPP1 to the bipolar phenotype.

The overall association is best characterized as Strong based on the identification of the missense variant in multiple patients (PMID:9682271) and the corroborative epigenetic data (PMID:38633806). Genetic evidence is rated as Strong since the coding variant and its recurrence provide significant support, whereas functional evidence is rated as Moderate because the experimental data, while compelling, derive from complementary epigenetic studies.

There is no evidence of conflicting data in the supplied reports; however, independent samples have shown variations in the strength of association. Additional studies may further refine the role of INPP1 in bipolar disorder, particularly its potential as a predictor of lithium response.

In conclusion, the integrated genetic and functional studies provide strong preliminary support for INPP1 as a candidate gene in bipolar disorder. Key take‑home: Assessing INPP1 variants could enhance diagnostic decision‑making and potentially guide therapeutic strategies in patients with bipolar disorder.

References

• Pharmacogenetics • 1998 • The polymorphic inositol polyphosphate 1-phosphatase gene as a candidate for pharmacogenetic prediction of lithium-responsive manic-depressive illness PMID:9682271
• Unspecified Journal • 2021 • DNA methylation alterations in INPP1 associated with suicidal behavior in bipolar disorder PMID:38633806

Evidence Based Scoring (AI generated)