rs116741562 (LINC01823/LINC01826): lncRNA GWAS variant

Key takeaways

• rs116741562 sits inside LINC01823 and LINC01826, two long non-coding RNA genes that regulate nearby gene activity without producing protein
• A UK Biobank GWAS of 141,261 participants identified dozens of genes shaping bone mineral density over time, with WNT signaling as the key enriched pathway
• In about 500,000 UK Biobank participants, fat-free mass (lean body mass) was independently linked to post-menopausal breast cancer risk, separate from any fat mass effect
• Long non-coding RNA variants are emerging as candidate bridges between body composition phenotypes and cancer susceptibility in large genetic studies
• Specific effect sizes for this variant are not reported in available study data, placing current evidence in the preliminary category

What the research says A longitudinal GWAS (genome-wide association study) of heel bone mineral density (BMD) in 141,261 white UK Biobank participants identified 52 genes associated with BMD trajectory mean and 114 genes associated with BMD within-subject variability, with the WNT signaling pathway and skeletal development gene sets highlighted by enrichment analyses, and findings replicated in Asian participants. Separately, an analysis of approximately 500,000 UK Biobank participants found that both whole body fat mass and fat-free mass are independently associated with post-menopausal breast cancer risk, and that long non-coding RNA regions can act as genetic links between body composition phenotypes and cancer susceptibility, as demonstrated by genome-wide significant associations at the LINC01488 locus.

Reported associations

• Bone mineral density trajectory: A GWAS of 141,261 UK Biobank participants found 52 genes tied to the mean BMD trajectory, with CPED1, WNT16, and FAM3C among the most significantly associated; gene-set enrichment pointed to the WNT signaling pathway and skeletal system development, with independent replication in an Asian cohort
• Bone mineral density within-subject variability: The same study identified 114 candidate genes associated with how much BMD fluctuated over time within individuals, suggesting a genetically distinct component of bone stability beyond average BMD level
• Post-menopausal breast cancer and fat-free mass: In approximately 500,000 UK Biobank participants, increasing whole body fat-free mass was associated with higher post-menopausal breast cancer risk independently of fat mass, and long non-coding RNA loci were identified as candidate mediators of this body composition-cancer relationship
• Colorectal cancer and fat-free mass: In the same cohort, increasing fat-free mass was independently associated with colorectal cancer risk in men

Evidence quality Both source studies used large UK Biobank cohorts (141,261 and approximately 500,000 participants), providing strong statistical power for genome-wide discovery. The BMD GWAS used a longitudinal trajectory-based analytical tool (TrajGWAS) and independently replicated its top findings in Asian participants, adding credibility to the broader set of identified BMD loci. The cancer and body composition study used convergent regression, principal component, and GWAS approaches, finding genome-wide significant associations (for example, p = 1.56 x 10^-17 and p = 1.78 x 10^-11) at lncRNA variants in a separate but related long non-coding RNA locus, LINC01488. However, the study reports provided here do not include explicit association statistics, effect sizes, or p-values specifically for rs116741562 at the LINC01823-LINC01826 locus, so the magnitude and statistical confidence of any association for this particular variant cannot be precisely characterized from available data, and the current evidence should be regarded as preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.