rs10750025 is a single nucleotide polymorphism (a single-letter variation in DNA) located near the DRD2 and TMPRSS5 genes. It has been identified in large genetic studies examining self-reported walking pace and substance use behaviors.

What does the DRD2 gene do?

DRD2 encodes the dopamine D2 receptor, a protein central to dopaminergic neurotransmission - the signaling system involved in reward, motor control, and behavioral responses to substances like nicotine and alcohol.

Is rs10750025 linked to smoking or drinking?

A GWAS of up to 1.2 million individuals found that dopaminergic genes, the category that includes DRD2, are associated with smoking initiation, cigarettes per day, smoking cessation, and drinks per week. The specific contribution of rs10750025 to those findings is tied to its location near this receptor gene.

What is the connection between rs10750025 and walking pace?

A genome-wide association study of 450,967 UK Biobank participants identified rs10750025 as one of 70 loci associated with self-reported walking pace. The same study found that walking pace is genetically correlated with cardiometabolic health and all-cause mortality, and Mendelian randomization suggested faster pace may be causally linked to lower cardiometabolic risk.

How does rs10750025 affect DRD2 gene expression?

GTEx data show that the alternate allele of rs10750025 is associated with increased DRD2 expression in peripheral tissues including the esophagus, colon, subcutaneous adipose tissue, and skin. Whether these peripheral expression changes have meaningful functional consequences is not established in current research.

rs10750025 (DRD2): Walking Pace and Dopamine Variant

Key takeaways

rs10750025 sits near DRD2 (dopamine receptor D2) and TMPRSS5, genes implicated in dopaminergic signaling
This variant was identified among 70 genome-wide significant loci in a GWAS of self-reported walking pace across 450,967 UK Biobank participants
A large GWAS of tobacco and alcohol use in up to 1.2 million individuals found dopaminergic pathway genes linked to smoking initiation and drinks per week
The alternate allele is associated with increased DRD2 expression in peripheral tissues including the esophagus, colon, adipose tissue, and skin
Walking pace heritability was estimated at only 13.2%, indicating that most variation in this trait is shaped by environment and lifestyle rather than genetics

What the research says A genome-wide association study of self-reported walking pace in 450,967 European-ancestry UK Biobank participants identified 70 independent loci at genome-wide significance (P < 5 x 10^-8), with SNP-based heritability estimated at 13.2% (standard error 0.21%), decreasing to 8.9% after adjustment for body mass index (BMI, a measure of weight relative to height). Genetic correlations were observed between the trait and cardiometabolic, respiratory, psychiatric, and mortality-related phenotypes, and Mendelian randomization analyses - a method for inferring causal effects using genetic variants as proxies - provided evidence for a potential causal link between faster walking pace and a lower cardiometabolic risk profile. A separate large-scale GWAS of tobacco and alcohol use in up to 1.2 million individuals identified 566 variants across 406 loci tied to smoking and drinking behaviors, explicitly reporting the involvement of dopaminergic neurotransmission - the signaling system in which the receptor gene is a key component.

Reported associations

Self-reported walking pace: rs10750025 was identified as one of 70 genome-wide significant loci in a GWAS of 450,967 European-ancestry adults; this phenotype shows genetic correlations with cardiometabolic, respiratory, and psychiatric traits and with all-cause mortality
Tobacco and alcohol use (dopaminergic pathway): A GWAS of up to 1.2 million individuals found dopaminergic pathway genes, the category encompassing the receptor gene, associated with smoking initiation (N = 1,232,091), cigarettes per day (N = 337,334), smoking cessation (N = 547,219), and drinks per week (N = 941,280); variance in these traits explained by genome-wide significant variants ranged from 0.1% (smoking cessation) to 2.3% (smoking initiation)

Evidence quality The walking pace GWAS (n = 450,967) is well-powered and reached the standard genome-wide significance threshold. The sample was restricted to European-ancestry participants, limiting generalizability to other populations, and self-reported walking pace is a less precise phenotype than objective measurement. The tobacco and alcohol use GWAS is among the largest substance use genetic studies published (up to 1.2 million participants), offering strong statistical power; however, individual variants account for only 0.1% to 2.3% of phenotypic variance, consistent with high polygenicity. The two studies suggest convergent biology around the receptor gene but do not directly confirm a specific functional outcome for this locus in the provided text, and no replication data for rs10750025 specifically are described. GTEx expression data provide a plausible molecular mechanism through increased expression of the receptor gene in peripheral tissues, but the clinical significance of those peripheral effects is not established by the provided evidence.

Tissue-specific expression effects

DRD2: The alternate allele is associated with increased expression in the esophageal gastroesophageal junction, esophageal muscularis, sigmoid colon, subcutaneous adipose tissue, and both sun-exposed and non-sun-exposed skin; all effects represent increased expression of the receptor gene GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

rs10750025 (DRD2): Walking Pace and Dopamine Variant

Key takeaways

Frequently asked questions

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