rs11743379 (LINC02899): Vaginal Microbiome Genetics

Key takeaways

• This variant was identified in a genome-wide association study linking host genetics to vaginal bacterial community composition in pregnant women.
• The study found 72 genome-wide significant associations between genetic variants and vaginal bacterial traits in 359 pregnant women.
• The alternate allele reduces LINC02899 gene expression in spleen, tibial nerve, and visceral fat tissue.
• Evidence comes from a single study in a Chinese pregnancy cohort and should be considered preliminary.

What the research says A genome-wide association study (GWAS, a large-scale scan linking genetic variants across the entire genome to measurable traits) of 359 pregnant Chinese women identified 72 associations between host genetic variants and vaginal bacterial traits (VBTs) at genome-wide significance (P < 5 x 10-8), with rs11743379 near the TRPC6P9-LINC02899 locus among the identified variants. Participants were grouped into five community state types (CSTs) based on vaginal bacterial composition, with CST-I (dominated by Lactobacillus crispatus) being the most prevalent at 37.3% of participants; most genome-wide significant variants had minor allele frequencies (MAFs, a measure of how common the rarer form of a variant is in the population) below 0.05, with only seven exceeding that threshold. The authors suggested that interferon signaling (a cellular communication pathway central to immune defense) may play an important role in shaping vaginal bacterial communities during pregnancy.

Reported associations

• Vaginal bacterial community traits (pregnancy): rs11743379 was identified as one of 72 genetic variants significantly associated with vaginal bacterial community composition in 359 pregnant Chinese women at genome-wide significance (P < 5 x 10-8, n=359); the specific bacterial trait linked to this locus is not detailed in the available study excerpt.

Evidence quality The sole study providing evidence for this locus enrolled 359 pregnant Chinese women, a modest cohort size for a GWAS. The genomic inflation factor (a diagnostic statistic indicating whether false positives are inflated by population structure) was reported below 1.1, suggesting the findings are unlikely to be an artifact of population stratification. The cohort consisted exclusively of Chinese pregnant women, limiting generalizability to other ethnicities and to non-pregnant populations. No independent replication cohort is reported in the available evidence, and the specific vaginal bacterial trait linked to rs11743379 is not specified in the available study text. All findings for this variant should be treated as preliminary.

Tissue-specific expression effects

• LINC02899: The alternate allele is associated with reduced gene expression in spleen, tibial nerve, and visceral adipose tissue (the fat surrounding internal abdominal organs) according to GTEx v11 data across 953 donors GTEx Portal. These are expression quantitative trait locus (eQTL) associations, meaning this variant correlates with how much LINC02899 RNA is produced in those tissues, and do not directly indicate a clinical outcome.

Lifestyle considerations No lifestyle considerations on file for this variant.