rs10498441 (NID2): Brain and Thyroid Gene Expression

Key takeaways

• rs10498441 was studied in the VA Million Veteran Program, a genome-wide study covering 635,969 people and 2,068 health traits
• The alternate allele reduces NID2 (Nidogen-2, a basement membrane protein) expression in two cerebellar brain regions but increases it in thyroid and liver
• A gene catalogued as ENSG00000294890 in the LINC02319 region shows reduced expression in three brain areas: hippocampus, substantia nigra, and cervical spinal cord
• RTRAF expression in thyroid is modestly elevated with this variant
• Specific disease or trait associations for rs10498441 are not enumerated in the available study text

What the research says The VA Million Veteran Program (MVP), a longitudinal study of 635,969 US Veterans from four genetic ancestry groups (African, Admixed American, East Asian, and European), conducted genome-wide association studies (GWASs - population-level scans linking genetic variants to health traits) across 2,068 traits, identifying 26,049 variant-trait associations total, with 3,477 detectable only after including non-European participants. GTEx v11 eQTL (expression quantitative trait loci - data linking genetic variants to how much of a gene is produced in a given tissue) analysis of 953 donors shows that rs10498441 has tissue-specific effects on NID2 and nearby gene expression, including opposite direction effects between brain and thyroid tissue. GTEx Portal

Reported associations No specific trait or disease associations for rs10498441 are described in the available MVP study text. The study covered 2,068 traits in 635,969 participants and identified 26,049 variant-trait associations overall, but the specific phenotype(s) linked to this locus are not listed in the provided excerpt. Gene expression associations from GTEx are described in the Tissue-specific expression effects section below.

Evidence quality The MVP GWAS enrolled 635,969 participants across four genetic ancestry groups, making it one of the largest and most diverse genome-wide association studies conducted to date. Statistical fine-mapping was applied across 57,601 independent signals to identify high-confidence causal variants, with 15,045 signals resolved to a single variant. The GTEx v11 eQTL data for rs10498441 is derived from 953 donors, with findings meeting an FDR<0.05 threshold (a standard requiring fewer than 5% of reported findings to be false discoveries) across brain, thyroid, and liver tissues. Trait-level association data specific to rs10498441 is not available in the provided sources, leaving its clinical relevance uncertain from the evidence at hand.

Tissue-specific expression effects

• NID2: The alternate allele is associated with reduced expression in the cerebellar hemisphere (slope -0.33) and cerebellum (slope -0.31), but increased expression in thyroid (slope +0.30) and liver (slope +0.22). Slope values are log2-normalized effects from GTEx v11, where positive indicates increased gene output and negative indicates decreased. The opposite direction between brain and thyroid tissue is notable. GTEx Portal
• ENSG00000294890 (LINC02319 region): The alternate allele is associated with reduced expression in cervical spinal cord (slope -0.60), substantia nigra (slope -0.46), and hippocampus (slope -0.45). These effect sizes are larger than those seen for NID2. GTEx Portal
• RTRAF: The alternate allele is associated with increased expression in thyroid tissue (slope +0.18). GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.