What you carry at this position in your DNA and what research says about it.
Weight and Diabetes Risk: 9/10 evidence, 18 publications.
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Sample genotype (not yours): T/T
Lowest Genetic Risk of Obesity and Diabetes
Carrying two copies of the protective T allele is associated with a lower body mass index and reduced risk of metabolic conditions. This genotype helps support a naturally leaner body profile.
What this genotype means: Lower average body mass index; Reduced risk of type 2 diabetes; Smaller average waist circumference.
Sample genotype (not yours): C/C
Typical Genetic Risk of Obesity and Diabetes
Carrying two copies of the common C allele represents the standard genetic baseline for weight and metabolic traits. This genotype does not provide the protective weight-loss benefits seen with the rare variant.
What this genotype means: Typical baseline body mass index; Standard population risk for type 2 diabetes; Typical waist circumference measurements.
Sample genotype (not yours): T/C
Lower Genetic Risk of Obesity and Diabetes
Carrying one copy of the protective T allele offers moderate protection against elevated body weight and metabolic risks. This helps buffer against genetic predispositions to weight gain.
What this genotype means: Slightly lower average body mass index; Mildly decreased risk of type 2 diabetes; Slightly smaller average waist circumference.
Gene function and biological role
Gene Function: The TMEM18 gene encodes a highly conserved transmembrane protein that is widely expressed in the brain, particularly within the hypothalamus which controls appetite and energy balance. It stands as one of the most robustly replicated genes associated with body mass index and childhood obesity in genetic research. Although its precise molecular mechanisms are still being uncovered, studies indicate it may influence nuclear envelope structure and neural cell migration. Genetic variations in and around this gene are believed to alter the neural pathways that govern eating behavior and metabolic rate.
Variant Impact: The rs2867125 variant is an intergenic genetic marker located on chromosome 2 in close proximity to the TMEM18 gene. This physical closeness means it serves as a strong proxy for regulatory changes affecting TMEM18 expression. The common C allele is consistently linked to higher body mass index and increased waist circumference across diverse populations. In contrast, the less common T allele is associated with a protective effect, predisposing carriers to a lower body weight and reduced metabolic risk.
Key Insight: This genetic variant influences weight primarily through the brain's appetite control centers rather than direct fat tissue metabolism.
Location: TMEM18. Chromosome 2 · 2p25.3 · 0.6 Mb
Estimated prevalence by population
Global 2.4%; European 3.0%; African 1.3%; East Asian 0.7%; South Asian 3.9%; Americas 1.6%; Ashkenazi 6.5%; Finnish 2.3%; Middle Eastern 2.9%; Amish 3.2%.
Estimated TT genotype frequency.
Global 25.2%; European 28.5%; African 20.2%; East Asian 14.8%; South Asian 31.8%; Americas 22.3%; Ashkenazi 38.1%; Finnish 25.9%; Middle Eastern 28.2%; Amish 29.4%.
Estimated TC genotype frequency.
Global 72.4%; European 68.5%; African 78.5%; East Asian 84.5%; South Asian 64.3%; Americas 76.0%; Ashkenazi 55.4%; Finnish 71.8%; Middle Eastern 68.9%; Amish 67.5%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Obesity & Body Composition
Body Mass Index. Evidence: 9/10. Source: PMID 20935630. Lower BMI.
Waist Circumference. Evidence: 8/10. Source: PMID 36329257. Smaller Waist.
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 28869590. Lower Risk.
Neurology & Mental Health
Addiction & Reward
Nicotine Dependence. Evidence: 8/10. Source: PMID 36477530. Lower Risk.
Showing effects for C/C genotype
Body Mass Index. Evidence: 9/10. Source: PMID 20935630. Typical BMI.
Waist Circumference. Evidence: 8/10. Source: PMID 36329257. Typical Waist.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 28869590. Typical Risk.
Nicotine Dependence. Evidence: 8/10. Source: PMID 36477530. Typical Risk.
Showing effects for T/C genotype
Body Mass Index. Evidence: 9/10. Source: PMID 20935630. Slightly Lower BMI.
Waist Circumference. Evidence: 8/10. Source: PMID 36329257. Slightly Smaller.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 28869590. Slightly Lower Risk.
Nicotine Dependence. Evidence: 8/10. Source: PMID 36477530. Slightly Lower Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Having two copies of the T allele provides the strongest genetic protection at this locus against weight gain and metabolic dysfunction. Large-scale genetic analyses show that individuals with this genotype tend to have a lower average body mass index and smaller waist circumference. This protective effect also translates to a significantly reduced risk of developing type 2 diabetes. Because TMEM18 is highly active in the brain's appetite-regulating centers, this variant may help naturally moderate food cravings and support healthier energy expenditure. Additionally, some research links this protective genotype to a lower likelihood of smoking initiation and fewer cigarettes smoked per day. Overall, these genetic factors work together to support long-term metabolic health.
Lower average body mass index; Reduced risk of type 2 diabetes; Smaller average waist circumference.
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele is the most common genetic profile globally, representing the baseline for the general population. This genotype is associated with typical susceptibility to weight gain, with studies showing slightly higher average body mass index and waist circumference compared to T-allele carriers. It also carries the standard population risk for type 2 diabetes, with a modest increase in odds compared to protective genotypes. Because this variant is located near the appetite-influencing TMEM18 gene, individuals with this profile may experience typical central signaling for hunger and satiety. Research also notes a standard baseline pattern for smoking behaviors and nicotine exposure. Because this is the global norm, standard healthy dietary choices and regular physical activity are highly effective ways to manage metabolic health.
Typical baseline body mass index; Standard population risk for type 2 diabetes; Typical waist circumference measurements.
Sample genotype: TC (Heterozygous)
Inheriting one copy of the protective T allele provides a moderate benefit compared to the common genotype. Research indicates that carriers of this heterozygous genotype generally maintain a slightly lower body mass index and reduced waist measurements than those with two copies of the risk allele. The presence of the T allele also offers a mild protective buffer against developing type 2 diabetes. Because TMEM18 is involved in central appetite regulation, having one protective allele may subtly influence satiety signals and eating behaviors. Studies also suggest a slightly lower tendency toward nicotine use and smoking intensity. While lifestyle factors remain highly influential, this genetic profile provides a helpful baseline advantage for metabolic wellness.
Slightly lower average body mass index; Mildly decreased risk of type 2 diabetes; Slightly smaller average waist circumference.
Variants with shared genetic architecture
rs13021737 · TMEM18 Gene · Chr 2 · Obesity Risk
rs6548238 · TMEM18 Gene · Chr 2 · Obesity Risk
rs7561317 · TMEM18 Gene · Chr 2 · Body Weight and BMI
Content updated August 2026.
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