rs11134531 (SLIT3): Aging and Physical Decline

Key takeaways

• rs11134531 in SLIT3 was flagged in a large genome-wide study of aging trajectories in UK Biobank participants.
• The genetics of physical decline are largely separate from those governing baseline physical fitness, with baseline function showing roughly ten times higher heritability.
• Physical decline was genetically linked to bone mineral density and telomere length, while cognitive decline was linked to Alzheimer's disease risk.
• Evidence for this specific variant is preliminary and comes from a single study with known limitations around longitudinal sample participation.

What the research says A 2025 genome-wide association study using UK Biobank longitudinal data (Schoeler, Pingault, and Kutalik, Nature Communications) identified rs11134531, located in or near the SLIT3 (Slit Guidance Ligand 3) gene, among loci associated with age-related decline. The study found that genetic contributors to baseline physical function and accelerated physical decline are largely distinct, with heritability estimates of approximately 31.38% for baseline physical function versus approximately 3.15% for the rate of physical decline. Mendelian Randomization analyses indicated that physical decline is partially influenced by genetic liability to reduced bone mineral density and shorter telomere length (standardized effects of gamma = -0.05 each), while cognitive decline was largely driven by Alzheimer's disease genetic liability (gamma = 0.17).

Reported associations

• Longitudinal aging phenotypes: rs11134531 in SLIT3 was identified in a genome-wide scan of physical and cognitive aging trajectories in UK Biobank participants (Schoeler et al., 2025); the specific associated trait, effect direction, and effect size for this locus are not detailed in the available study text.

Evidence quality The sole available study is a 2025 genome-wide effort by Schoeler, Pingault, and Kutalik (Nature Communications) using UK Biobank prospective two-wave data covering physical measures (grip strength, forced expiratory volume, fitness) and cognitive measures (reaction time, fluid intelligence). The longitudinal design is more informative than cross-sectional approaches, but the authors explicitly flag selective attrition as a potential source of bias, as healthier individuals are more likely to return for a second assessment. The study validated two-wave change models in simulations before applying them genome-wide, lending methodological credibility. The heritability of physical decline is notably low (approximately 3.15%), meaning individual variant effects are likely modest. The specific p-value, allele frequency, and effect size for rs11134531 are not available in the provided study excerpt, and independent replication has not been reported. Evidence for this variant should be considered preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.