rs117840759 (GOPC-NEPNP): Brain Connectivity Variant

Key takeaways

• This variant, in the GOPC-NEPNP region, was identified in a large genome-wide study of how the brain's myelinated nerve fibers connect different brain regions
• The study analyzed 206 measures of structural brain connectivity in over 26,000 UK Biobank participants using diffusion MRI brain scans
• A nearby gene, DCBLD1, shows increased expression in thyroid tissue and reduced expression in whole blood for carriers of this variant, based on independent tissue expression data
• Structural connectivity is highly polygenic: roughly 9 in 100 common genetic variants are estimated to influence each connectivity measure studied

What the research says A genome-wide association study (GWAS) -- a large-scale scan linking genetic variants to a measurable trait -- of 206 structural connectivity measures derived from diffusion magnetic resonance imaging (dMRI) tractography was conducted in 26,333 UK Biobank participants, and the GOPC-NEPNP region emerged among variants associated with white-matter structural connectivity, defined as the density of myelinated (insulated) axon bundles connecting pairs of brain regions. The study identified 30 independent variants surviving Bonferroni correction (a strict statistical threshold accounting for the 206 measures tested) and 96 more at nominal genome-wide significance; the provided text does not report a specific p-value or effect size for rs117840759 individually. Structural connectivity measures were found to be highly polygenic, with a median of 9.1% of common genetic variants estimated to have non-zero effects on each measure, and showed signatures of negative selection, suggesting evolutionary pressure against connectivity-altering mutations.

Reported associations

• White-matter structural connectivity: the GOPC-NEPNP region, containing rs117840759, was implicated in a GWAS of 206 dMRI-based structural connectivity measures in 26,333 UK Biobank participants; the provided study text does not report a specific effect size or named connectivity measure for this variant alone
• DCBLD1 gene expression - thyroid tissue: the alternate allele is associated with increased expression of the nearby DCBLD1 gene in thyroid tissue (slope +0.48, p=8.1e-5) GTEx Portal
• DCBLD1 gene expression - whole blood: the alternate allele is associated with reduced DCBLD1 expression in whole blood (slope -0.42, p=6.1e-6) GTEx Portal

Evidence quality The GWAS was conducted in 26,333 UK Biobank participants and applied Bonferroni correction across 206 connectivity measures; 30 variants reached that corrected threshold and 96 more reached nominal genome-wide significance. The provided study text does not state a specific p-value, odds ratio, or beta coefficient for rs117840759 individually, and independent external replication is not described in the supplied material. The study noted that structural connectivity traits are highly polygenic, which generally implies small per-variant effect sizes. The GTEx eQTL (expression quantitative trait locus -- a genetic variant correlated with how much of a gene is produced in a tissue) findings for DCBLD1 come from GTEx v11 (953 donors, FDR<0.05) and reflect tissue-level expression associations pointing toward a potential mechanism rather than clinical outcomes; the opposing directions in thyroid versus whole blood may reflect tissue-specific regulatory contexts and should not be overinterpreted without further study.

Tissue-specific expression effects

• DCBLD1: the alternate allele is associated with increased expression in thyroid tissue and reduced expression in whole blood, with the two tissues showing opposite directions of effect, suggesting tissue-specific regulatory roles for this locus GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.