MEIS1 rs12927866: What Your Genotype Means
The rs12927866 variant is a common genetic change located within the MEIS1 gene. It has been identified by researchers as a risk locus associated with restless legs syndrome (RLS), a condition characterized by an uncontrollable urge to move the legs.
What each genotype means
Typical RLS risk
You carry two copies of the common C allele at rs12927866 in the MEIS1 gene region. In population-based studies, this baseline genotype is not associated with the increased risk of restless legs syndrome (RLS) or periodic limb movements in sleep linked to the alternative allele. However, RLS is a complex trait influenced by overall genetics, iron levels, and lifestyle factors, so having this genotype does not rule out developing symptoms.
Carried by approximately 45% to 50% of individuals of European ancestry, and generally more common in East Asian and African populations.
Moderately increased RLS risk
You carry one copy of the T risk allele at rs12927866 in the MEIS1 gene. Large genome-wide association studies show that each copy of this allele is statistically associated with a higher likelihood of developing restless legs syndrome (RLS) and periodic limb movements in sleep. This genetic marker represents a statistical susceptibility factor rather than a direct diagnosis or certainty of experiencing symptoms.
Carried by roughly 40% to 45% of individuals in European ancestry cohorts.
Elevated RLS risk
You carry two copies of the T risk allele at rs12927866 in the MEIS1 locus. Research indicates that homozygous carriers have the strongest statistical association with restless legs syndrome (RLS) and increased periodic limb movements during sleep among genotypes at this marker. While this genotype confers a higher relative genetic risk, it does not diagnose RLS or guarantee you will develop sleep-related movement symptoms.
Present in approximately 8% to 10% of individuals of European ancestry; observed at lower frequencies in most other global ancestries.
Understanding the Variant
The rs12927866 variant is a single nucleotide polymorphism (SNP) located within the MEIS1 gene. Specifically, it is an intronic variant, meaning it resides in a non-coding region of the gene that does not provide instructions for making a protein. Instead, these regions often act as regulatory switches that control when and how much of a gene is expressed. Research indicates that this specific locus contains highly conserved non-coding regions that function as enhancers in the developing telencephalon, a part of the forebrain. By altering these regulatory elements, the variant may influence the expression levels of MEIS1 during critical periods of brain development, which is hypothesized to contribute to the underlying biology of restless legs syndrome.
The Role of the MEIS1 Gene
MEIS1 encodes a homeobox transcription factor, a type of protein that acts as a master regulator by binding to DNA and controlling the activity of many other genes. It plays a vital role in the development of the central nervous system, particularly in the specification of neuronal progenitors in the ganglionic eminences of the brain. Studies in animal models, such as mice and zebrafish, have shown that MEIS1 is essential for proper neurogenesis and the differentiation of inhibitory neurons. When MEIS1 function is disrupted or its expression is altered, it can lead to behavioral changes, such as hyperactivity in mice, which researchers use as a model to study the mechanisms of RLS. The gene is part of a complex regulatory network that remains a major focus of neurodevelopmental research.
Research and Evidence Strength
The association between MEIS1 variants and restless legs syndrome is considered one of the strongest genetic signals identified for the condition through genome-wide association studies (GWAS). However, the evidence for rs12927866 specifically is categorized as limited in terms of its individual clinical utility. While large-scale studies have consistently linked the MEIS1 locus to RLS, the condition is polygenic, meaning it is influenced by many different genetic variants, each contributing a small amount to the overall risk. Furthermore, the exact biological pathway connecting this specific intronic variant to the clinical symptoms of RLS is still being investigated. Current research emphasizes that while these genetic findings are significant for understanding the disease's architecture, they do not currently serve as a diagnostic tool for individuals.
Population Frequency
The rs12927866 variant is considered a common SNP in the general population. Because it is common, a large portion of the global population carries at least one copy of the variant. Its frequency does not necessarily indicate disease status, as many individuals who carry the variant do not develop restless legs syndrome. RLS itself is a complex condition with a prevalence estimated between 3.9% and 14.3% in adult populations, and it is known to be more common in women and to increase in frequency with age. The presence of this variant is just one of many factors, including environmental and other genetic influences, that determine an individual's susceptibility to the condition.
What This Information Means for You
It is important to understand that genetic variants like rs12927866 are markers of statistical association rather than direct causes of disease. Having this variant does not mean you will develop restless legs syndrome, and not having it does not guarantee you will not. This information is intended for educational purposes to help you understand the current state of genomic research. If you are experiencing symptoms such as uncomfortable sensations in your legs or an irresistible urge to move them, especially at night, you should consult a healthcare professional. They can provide a proper clinical evaluation, discuss your medical history, and determine if any treatment or lifestyle adjustments are appropriate for your specific situation. Never use genetic information to self-diagnose or alter any medical treatment plans.
How common is this variant?
The rs12927866 variant is a common SNP found across diverse ancestral populations, with its specific genotypes appearing at high frequencies in the general public.
Frequently asked questions
Does having the MEIS1 variant mean I have restless legs syndrome?
No. The variant is associated with an increased statistical risk of RLS, but it is not a diagnostic test. Many people carry this variant and never develop the condition.
Can I use this genetic information to prevent RLS?
Currently, there are no established preventative measures based on this specific genetic variant. RLS is a complex condition influenced by many factors, and you should discuss any health concerns with your doctor.
Is MEIS1 the only gene linked to restless legs syndrome?
No. RLS is a polygenic disorder, meaning it is associated with many different genetic loci. Other genes, such as BTBD9 and SKOR1, have also been identified in research studies.
Should I get tested for this variant?
Genetic testing for common variants like rs12927866 is not typically used in clinical practice for diagnosing RLS. Clinical diagnosis is based on symptoms and medical history evaluated by a healthcare provider.
Sources & further reading
Educational information only, last refreshed 10/24/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A fine-mapped regulatory variant within the MEIS1 locus associated with restless legs syndrome and periodic limb movements during sleep.
This intronic variant in the MEIS1 gene is one of the most robustly replicated genetic risk factors for restless legs syndrome (RLS) and periodic limb movements of sleep.
Intronic SNP strongly predisposing individuals to Restless Legs Syndrome and periodic limb movements during sleep.
Intronic regulatory variant within MEIS1 strongly implicated in periodic limb movements during sleep and restless legs syndrome etiology.
A 3' UTR variant in MEIS1 associated with periodic limb movement in sleep, restless legs syndrome, and insomnia symptoms.
Non-coding regulatory variant in MEIS1 that is strongly associated with periodic limb movements during sleep and symptom severity in restless legs syndrome.