rs10900325 (FMO5): Brain and testis expression variant
Key takeaways
- The alternate allele reduces FMO5 expression in testis but increases it in aortic artery tissue and immune cells
- The same variant reduces CHD1L expression across four brain regions including the caudate and putamen, and in thyroid tissue
- These are gene expression associations, not direct disease outcome findings
- Statistical significance is strong across tissues, with the thyroid CHD1L association reaching p=8.9e-14
- No GWAS-level phenotypic associations for this variant are reported in the provided research
Key takeaways
- The alternate allele of rs10900325 reduces FMO5 expression in testis but increases it in aortic artery tissue and immune cells
- This variant also reduces CHD1L expression across four brain regions (caudate, putamen, nucleus accumbens, hypothalamus) and in thyroid tissue
- These findings are gene expression associations (eQTL data), not direct disease outcome findings
- Statistical significance is strong in several tissues, with the thyroid CHD1L association reaching p=8.9e-14
- No GWAS-level phenotypic associations for this variant are reported in the provided research
What the research says GTEx v11 data (953 donors, FDR below 0.05) identifies rs10900325 as an expression quantitative trait locus (eQTL, a genetic variant that predicts how much of a gene is produced in a given tissue) for two genes: FMO5 (flavin-containing monooxygenase 5) and CHD1L (chromodomain helicase DNA binding protein 1-like); effect sizes are in log2-normalized expression units per alternate allele GTEx Portal. For FMO5, the alternate allele has opposite effects depending on tissue: reduced expression in testis (effect -0.36) versus increased expression in aortic artery (+0.28) and EBV-transformed lymphocytes (+0.34) GTEx Portal. For CHD1L, the alternate allele consistently reduces expression in the basal ganglia (a set of brain structures involved in motor control and learning), including the caudate (-0.42, p=1.2e-9), putamen (-0.36), nucleus accumbens (-0.32), and hypothalamus (-0.31), as well as thyroid tissue (-0.29, p=8.9e-14) GTEx Portal.
Reported associations
- FMO5 expression, testis: The alternate allele is associated with reduced expression (effect -0.36 log2 units, p=8.6e-7) GTEx Portal
- FMO5 expression, EBV-transformed lymphocytes: The alternate allele is associated with increased expression (effect +0.34 log2 units, p=1.2e-5) GTEx Portal
- FMO5 expression, aortic artery: The alternate allele is associated with increased expression (effect +0.28 log2 units, p=3.2e-7) GTEx Portal
- CHD1L expression, caudate (basal ganglia): The alternate allele is associated with reduced expression (effect -0.42 log2 units, p=1.2e-9) GTEx Portal
- CHD1L expression, putamen (basal ganglia): The alternate allele is associated with reduced expression (effect -0.36 log2 units, p=2.8e-7) GTEx Portal
- CHD1L expression, nucleus accumbens (basal ganglia): The alternate allele is associated with reduced expression (effect -0.32 log2 units, p=4.4e-6) GTEx Portal
- CHD1L expression, hypothalamus: The alternate allele is associated with reduced expression (effect -0.31 log2 units, p=3.0e-7) GTEx Portal
- CHD1L expression, thyroid: The alternate allele is associated with reduced expression (effect -0.29 log2 units, p=8.9e-14) GTEx Portal
Evidence quality The primary evidence for rs10900325 comes from eQTL data in GTEx v11 (953 donors, cis-window analysis, FDR below 0.05). Associations are statistically robust across tissues, with p-values ranging from 1.2e-5 (FMO5 in lymphocytes) to 8.9e-14 (CHD1L in thyroid). This evidence describes changes in gene expression levels rather than direct disease or trait outcomes; the functional and phenotypic consequences of these expression changes are not established from eQTL data alone. Two provided GWAS studies cover related territory but do not explicitly report rs10900325 among their findings: a longitudinal GWAS on late-life memory performance and decline (n=27,633 for performance; n=22,365 for decline) identified several novel loci without listing this variant, and a cross-population phenome-wide atlas of 220 traits across up to 628,000 participants (BioBank Japan, UK Biobank, FinnGen) reported approximately 5,000 new loci without explicitly identifying this variant in the provided materials. Direct phenotypic associations for rs10900325 therefore remain to be established.
Tissue-specific expression effects
- FMO5: The alternate allele reduces expression in testis and increases it in EBV-transformed lymphocytes and aortic artery tissue; effects run in opposite directions depending on tissue context GTEx Portal
- CHD1L: The alternate allele consistently reduces expression across four brain regions (caudate, putamen, nucleus accumbens, hypothalamus) and thyroid tissue, with the strongest effect in the caudate (effect -0.42) GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10900325?
rs10900325 is a genetic variant near the FMO5 gene whose alternate allele affects how much FMO5 and CHD1L are produced in various tissues. For FMO5, the effect differs by tissue: expression goes down in testis but up in blood vessels and immune cells.
What does the FMO5 gene do?
FMO5 encodes flavin-containing monooxygenase 5, an enzyme involved in metabolism. The available research focuses on how rs10900325 influences FMO5 expression levels across tissues rather than the full range of FMO5 functions.
Is rs10900325 linked to any diseases?
No direct disease associations for rs10900325 are reported in the provided studies. The available evidence is limited to gene expression (eQTL) data from GTEx, showing this variant alters FMO5 and CHD1L activity across tissues.
What brain regions are affected by rs10900325?
GTEx data shows the alternate allele reduces CHD1L expression in the caudate, putamen, nucleus accumbens, and hypothalamus. These structures are part of the basal ganglia network, involved in motor control and learning.
What is an eQTL and why does it matter here?
An eQTL (expression quantitative trait locus) is a genetic variant that predicts how much of a specific gene is produced in a tissue. rs10900325 acts as an eQTL for both FMO5 and CHD1L, meaning people with different alleles tend to show different gene expression levels in those tissues.