rs116401702 (HEYL): Medication Use and BMI Variant

Key takeaways

• rs116401702 sits in the HEYL gene region and has been catalogued in genetic studies covering total medication use, body mass index, and blood or urine biomarkers
• The variant's alternate allele is linked to increased expression of OXCT2P1, a neighboring gene, across eight tissue types in GTEx v11 eQTL data
• The associated studies involved between 335,000 and over 1.1 million participants, providing large sample sizes for genome-wide discovery
• Specific clinical effect sizes for this variant are not available in the provided study excerpts, which limits precise interpretation

What the research says A genome-wide association study (GWAS, a method that scans large numbers of genetic variants across many individuals to find statistically significant associations) of total medication use in 335,744 unrelated UK Biobank participants found 59 independent genetic loci, with common variants together explaining approximately 18% of variation in medication burden; the largest share of that genetic variance came from variants with low-to-medium minor allele frequency. A separate BMI GWAS identified 906 loci reaching genome-wide significance in approximately 1.1 million European-ancestry participants and 41 loci in approximately 100,000 African-ancestry participants, and a genetic risk score combining 2,446 BMI-associated variants was linked to 316 clinical diagnoses in a large veterans health database, with 96.5% of those diagnoses showing elevated risk. A third study mapped the genetics of 35 clinical laboratory biomarkers in 363,228 UK Biobank participants, identifying 1,857 associated loci and 51 causal relationships via Mendelian randomization (a technique that uses genetic variants as proxies to test whether an exposure causally influences an outcome), with common variants explaining varying fractions of heritability across the 35 biomarkers.

Reported associations

• OXCT2P1 tissue expression: The alternate allele of rs116401702 is associated with increased OXCT2P1 expression in the esophagus (gastroesophageal junction and muscularis), sigmoid colon, tibial artery, cultured fibroblasts, breast mammary tissue, visceral adipose omentum, and lung; effect slopes range from approximately +0.57 to +0.75 on a log2-normalized scale GTEx Portal
• Medication use: This variant has been examined within the scope of a UK Biobank GWAS that identified 59 loci for total medication use (n=335,744); specific per-variant effect sizes for rs116401702 are not available in the provided study text
• Body mass index: This variant has been examined within a large multi-cohort BMI GWAS spanning approximately 1.1 million European-ancestry and 100,000 African-ancestry participants; specific per-variant effect sizes for rs116401702 are not available in the provided study text
• Blood and urine biomarkers: This variant has been examined within a UK Biobank analysis of 35 clinical laboratory measurements (n=363,228); specific biomarker associations for rs116401702 are not available in the provided study text

Evidence quality The three GWAS studies linked to this variant used large, well-powered samples ranging from 335,744 to over 1.1 million participants. The biomarker study applied a Bonferroni-corrected significance threshold (p < 5x10^-9 for imputed variants) and meta-analyzed results across five ancestry groups. The GTEx v11 eQTL data for OXCT2P1 used 953 donors at FDR < 0.05; the tibial artery signal reaches p=9.3x10^-10 and the esophageal muscularis signal reaches p=1.6x10^-7, indicating robust tissue-expression associations. No specific replication data for rs116401702 are reported in the provided study excerpts, and per-variant effect sizes for the clinical trait associations are absent, which limits the strength of clinical interpretation.

Tissue-specific expression effects

• OXCT2P1: The alternate allele is associated with increased expression in eight tissues: esophageal gastroesophageal junction, esophageal muscularis, sigmoid colon, tibial artery, cultured fibroblasts, breast mammary tissue, visceral adipose omentum, and lung; the statistically strongest signals are in the tibial artery (p=9.3x10^-10) and esophageal muscularis (p=1.6x10^-7) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.