rs113889867 (STMN2): SSRI Antidepressant Response
Key takeaways
- rs113889867 is a variant at the STMN2 locus, a gene encoding a neuronal microtubule-regulating protein
- It appears in a genome-wide pharmacogenomics study of SSRI antidepressant response in depression involving up to 2,394 participants
- No variant in that study reached genome-wide statistical significance after replication, making all findings preliminary
- GTEx data from 953 donors show the ALT allele is linked to reduced STMN2 expression in heart left ventricular tissue
Key takeaways
- rs113889867 is a variant at the STMN2 locus, a gene encoding Stathmin-2, a microtubule-regulating protein involved in neuronal growth
- It appears in the dataset of the International SSRI Pharmacogenomics Consortium (ISPC), a multi-center genome-wide study of antidepressant treatment response in major depressive disorder
- No variant in the ISPC study achieved genome-wide statistical significance after replication across a combined sample of 2,394 subjects, making findings preliminary
- GTEx data from 953 donors link this variant's ALT allele to reduced STMN2 expression specifically in heart left ventricular tissue
What the research says
rs113889867 sits at the STMN2 (Stathmin-2; a microtubule-destabilizing protein critical to axonal regeneration and neuronal maintenance) locus and is present in data from the International SSRI Pharmacogenomics Consortium (ISPC), a genome-wide association study (GWAS) measuring 4-week treatment outcomes - quantified with the 17-item Hamilton Rating Scale for Depression - among 865 patients with major depressive disorder (MDD) drawn from seven international sites across Europe, North America, and Asia; a subsequent meta-analysis incorporating the PGRN-AMPS and STAR*D replication cohorts reached N=2,394, yet no variant cleared the standard genome-wide significance threshold (P<5×10^-8) after replication, and the authors noted that the study had limited statistical power for such a complex pharmacogenomic trait. Separately, expression quantitative trait locus (eQTL) data from GTEx v11 (953 donors, cis-window, FDR<0.05) indicate that the ALT allele of rs113889867 is associated with reduced expression of STMN2 (ENSG00000296852) in the heart left ventricle, with a slope of −0.43 GTEx Portal.
Reported associations
- SSRI antidepressant treatment response (major depressive disorder): This variant is present in the ISPC GWAS dataset, which examined response to several different SSRIs; however, the study's reported top signals in the meta-analysis of response mapped to the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4) / VSTM5 (V-set and transmembrane domain containing 5) region (P=5.03×10^-8, approaching but not clearing genome-wide significance) and 5′ upstream of NRG1 (neuregulin-1; P=1.20×10^-6) - no specific association statistic for rs113889867 is documented in the provided study materials, and the authors explicitly stated that top findings were not replicated across cohorts.
- Heart left ventricular STMN2 expression (eQTL): The ALT allele is associated with reduced expression of this gene in heart left ventricle tissue, with a slope of −0.43 (FDR<0.05) GTEx Portal.
Evidence quality
Evidence bearing specifically on rs113889867 is preliminary and indirect. The ISPC GWAS - the sole clinical study in the provided materials - enrolled 865 subjects at discovery and reached N=2,394 in meta-analysis, sample sizes the authors themselves characterized as underpowered for this trait; the study failed to yield any genome-wide significant hit, and its top associations were not replicated in independent cohorts. No variant-specific association statistic for rs113889867 is reported in the provided text. The GTEx eQTL finding (heart left ventricle, slope −0.43, FDR<0.05, N=953 donors) provides mechanistic rather than clinical evidence - it describes how this variant relates to gene expression levels in a specific tissue, not to any disease or treatment outcome - and the biological significance of reduced STMN2 expression in cardiac tissue is not established by the available data GTEx Portal. Taken together, the evidence base for this variant is too limited to draw firm conclusions.
Tissue-specific expression effects
- STMN2 (ENSG00000296852): The ALT allele is associated with reduced expression in heart left ventricle tissue; no other tissues reached significance in the provided GTEx data GTEx Portal.
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What is the STMN2 gene?
STMN2 encodes Stathmin-2, a protein that regulates microtubules - the structural scaffolding inside cells - and plays a role in neuronal growth and axonal maintenance. The rs113889867 variant is located at this gene locus.
Is rs113889867 linked to antidepressant response?
This variant appears in data from the International SSRI Pharmacogenomics Consortium, a genome-wide study of SSRI treatment outcomes in major depressive disorder involving up to 2,394 participants. However, no specific significant association was documented for this variant in the available study results, and the study's top findings were not replicated.
What does the GTEx eQTL finding mean for rs113889867?
An eQTL is a variant that predicts how much a nearby gene is expressed in a particular tissue. GTEx data show the ALT allele of rs113889867 is associated with reduced STMN2 expression in heart left ventricular tissue. This is a mechanistic finding about gene regulation, not a direct clinical association with any disease.
How strong is the evidence for rs113889867?
Evidence is preliminary. The only clinical study in the available data did not achieve genome-wide statistical significance for any variant, and no specific result for rs113889867 was reported in the provided materials. The cardiac expression finding from GTEx is mechanistic and has not been linked to a health outcome in the provided data.
What was the ISPC pharmacogenomics study?
The International SSRI Pharmacogenomics Consortium (ISPC) was a collaboration across seven international sites that performed a genome-wide association study of 4-week treatment response to SSRI antidepressants in patients with major depressive disorder, using 865 discovery subjects and a meta-analysis reaching 2,394 total participants.