rs11890236 (LINC01965): Childhood Obesity GWAS Locus

Key takeaways

• rs11890236 sits in the LINC01965 - AHCYP3 region, containing a long intergenic non-coding RNA (LINC01965) and an adenosylhomocysteinase pseudogene (AHCYP3).
• The locus was identified in a genome-wide association study (GWAS) of childhood obesity in 815 Hispanic children.
• The alternative allele at this variant is linked to increased gene expression in testis tissue in population-level data.
• Evidence for this variant's specific functional role is preliminary, and neither gene at the locus is well-characterized in obesity research.

What the research says The VIVA LA FAMILIA Study genotyped 1.1 million single nucleotide polymorphisms (SNPs) in 815 Hispanic children from 263 families in Houston, TX, searching for genetic loci linked to childhood obesity and related biological processes -- including anthropometry, body composition, metabolites, hormones, inflammation, diet, energy expenditure, and physical activity. That study identified several novel genetic loci, including genes described as having unknown function in obesity pathogenesis, expanding the catalog of candidate biological pathways in pediatric metabolic health. Separately, tissue-specific expression data from GTEx v11 (953 donors) shows the alternative allele at rs11890236 is associated with increased expression of a gene at this locus (ENSG00000298919) specifically in testis tissue (slope +0.41 on a log2 scale, p=5.3e-6) GTEx Portal.

Reported associations

• Childhood obesity and related traits: This locus was flagged in the VIVA LA FAMILIA GWAS examining obesity-related phenotypes in Hispanic children, including body composition, metabolic markers, inflammatory markers, energy expenditure, and physical activity; specific association statistics for rs11890236 are not reported in the available study excerpt.
• Testis gene expression (eQTL): The alternative allele is associated with increased expression of ENSG00000298919 in testis tissue (slope +0.41 on a log2 scale, p=5.3e-6) in GTEx v11 data GTEx Portal.

Evidence quality The VIVA LA FAMILIA Study enrolled 815 Hispanic children from 263 families ascertained on obese probands (BMI above the 95th percentile, ages 4-19), using Illumina Infinium technology across 1.1 million SNPs. The study is notable for its broad phenotyping and its focus on the Hispanic pediatric population, which has historically been underrepresented in GWAS research. However, the available study text does not include specific association statistics for rs11890236 itself, and neither LINC01965 nor AHCYP3 is named in the study abstract, limiting interpretation of the precise link between this variant and any specific trait. The GTEx expression quantitative trait locus (eQTL) signal in testis meets the study-wide false discovery rate threshold (FDR<0.05), with p=5.3e-6 and effect size +0.41 on log2-normalized expression GTEx Portal; no other tissue reached significance in GTEx v11, and the biological relevance of testis-specific expression for this locus has not been established. No replication data are available from the provided sources, and the overall evidence base for this variant is preliminary.

Tissue-specific expression effects

• ENSG00000298919: The alternative allele is associated with increased expression in testis tissue; no other tissues reached significance in GTEx v11 data (953 donors, FDR<0.05) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.