thyroxine to 8-methoxykynurenate

Numerator Metabolite

Structure of thyroxine
Metabolite Accession: GCST90200293
Name: thyroxine
Hmdb Id: HMDB0000248
Super Pathway: NA
Sub Pathway: NA
Inchikey: XUIIKFGFIJCVMT

Denominator Metabolite

Structure of 8-methoxykynurenate
Metabolite Accession: GCST90200186
Name: 8-methoxykynurenate
Hmdb Id: HMDB0060426
Super Pathway: NA
Sub Pathway: NA
Inchikey: BXZSKDOPGDPDEG

Associated Genomic Regions

Region: rs4148324

Click a 'Plot' button in the tables to the right to view a locus plot here.

Clumped rQTL variant

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SNP Summary

Chr:
2
Beta (Ratio):
-0.203
Position:
234672722
SE (Ratio):
0.024
Effect Allele:
G
Z-score (Ratio):
-8.481
Reference Allele:
T
-log10(P):
-38.341
MAF:
0.323
Beta (Num):
-0.096
Novel Locus:
Yes ✔️
SE (Num):
0.016
Beta (Den):
0.107
SE (Den):
0.018
No CNV overlap
rQTL cluster:
138
Reaction Distance:
NA
Closest Genes:
UGT1A10 UGT1A3 UGT1A5 UGT1A8 UGT1A1

LLM Analysis

Numerator Metabolite Explanation:

Thyroid hormone biosynthesis/metabolism.5[1], 6[2], 7[3], 8[4]

Denominator Metabolite Explanation:

Tryptophan metabolism (Kynurenine pathway).9[1], 10[2], 11[3], 12[4]

Ratio Explanation:

Decreased UGT1A1 function reduces thyroxine glucuronidation, potentially increasing thyroxine levels relative to metabolites from other pathways not primarily dependent on UGT1A1.13[1], 14[2], 15[3]

Ratio Evidence:

metabolites not in a pathway but enzyme catalyzes one metabolite

Gene Ratio Phenotype Relationship:

Reduced UGT1A1 activity, linked to cholelithiasis, impairs glucuronidation of both bilirubin and thyroxine.1[1], 13[2], 14[3] This impairment, along with thyroxine's known effects on cholesterol metabolism and bile flow, likely contributes to gallstone formation.16[4], 17[5], 18[6], 19[7]

Phenotype Driver:

Gene-centric:UGT1A1

Downloads

Download the full rQTL summary statistics file for this metabolite ratio. Data contains the loci listed here. For each SNP (chromosome, effect_allele, reference_allele, pos_name, position) these columns contain the summary statistics of the ratio (beta, pgain, pval, se, z), the numerator metabolite (beta_1, pval_1, n_iids_1, effect_allele_frequency_1, se_1, z_1) and the denominator metabolite (beta_2, pval_2, n_iids_2, effect_allele_frequency_2, se_2, z_2)

Download rQTL Data