What you carry at this position in your DNA and what research says about it.
Weight and Diabetes Risk: 10/10 evidence, 36 publications.
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Sample genotype (not yours): G/G
Lower Risk of Weight Gain and Diabetes
Lower body mass index and a reduced risk of type 2 diabetes are associated with the G/G genotype. Slightly higher diastolic blood pressure may also be present as a minor trade-off.
What this genotype means: Lower predisposition to obesity; Reduced risk of type 2 diabetes; Slightly higher diastolic blood pressure.
Sample genotype (not yours): A/A
Higher Risk of Weight Gain and Diabetes
Higher body mass index and an increased risk of type 2 diabetes are linked to the A/A genotype. This metabolic predisposition is often accompanied by a tendency to accumulate more visceral fat.
What this genotype means: Higher predisposition to obesity; Increased risk of type 2 diabetes; Slightly lower diastolic blood pressure.
Sample genotype (not yours): G/A
Typical Risk of Weight Gain and Diabetes
Typical metabolic outcomes are expected with this heterozygous genotype. Predisposition for body mass index, blood sugar levels, and blood pressure remains close to the population average.
What this genotype means: Typical body mass index; Standard risk of type 2 diabetes; Average blood pressure levels.
Gene function and biological role
Gene Function: The ZC3H4 gene encodes a zinc finger protein that plays a key role in RNA processing and transcriptional regulation. It is highly expressed in metabolic tissues, including adipose tissue and the liver, where it helps modulate cellular responses to nutrient availability. Research suggests that ZC3H4 is involved in adipogenesis, the process by which cells develop into mature fat cells [1]. By regulating the expression of genes involved in lipid storage, it directly influences body fat distribution and overall metabolic health [1].
Variant Impact: The rs3810291 variant is located in the 3 prime untranslated region of the ZC3H4 gene. This specific location is crucial because untranslated regions contain binding sites for regulatory molecules that control gene expression levels. The G to A change at this position is thought to alter the stability or translation efficiency of the ZC3H4 transcript, thereby modifying its abundance in metabolic tissues. Consequently, this single-nucleotide change influences a wide array of downstream metabolic traits, ranging from body fat accumulation to glucose regulation [2].
Key Insight: The same genetic variant that increases the risk of weight gain and type 2 diabetes is also linked to higher self-reported physical activity levels and slightly lower diastolic blood pressure.
Location: ZC3H4. Chromosome 19 · 19q13.32 · 47.1 Mb
Estimated prevalence by population
Global 29.5%; European 10.5%; African 65.9%; East Asian 52.3%; South Asian 34.1%; Americas 22.1%; Ashkenazi 12.4%; Finnish 14.2%; Middle Eastern 18.3%; Amish 12.8%.
Estimated GG genotype frequency.
Global 41.1%; European 43.8%; African 30.6%; East Asian 40.0%; South Asian 48.6%; Americas 49.8%; Ashkenazi 45.6%; Finnish 47.0%; Middle Eastern 49.0%; Amish 46.0%.
Estimated GA genotype frequency.
Global 29.4%; European 45.6%; African 3.5%; East Asian 7.7%; South Asian 17.3%; Americas 28.1%; Ashkenazi 42.0%; Finnish 38.8%; Middle Eastern 32.7%; Amish 41.2%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Obesity & Body Composition
Body Mass Index. Evidence: 10/10. Source: PMID 20935630. Lower BMI.
Visceral Fat. Evidence: 7/10. Source: PMID 31501611. Lower Accumulation.
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 30297969. Lower Risk.
Hypertension
Diastolic Blood Pressure. Evidence: 8/10. Source: PMID 33230300. Slightly Higher.
Lipids & Cholesterol
HDL Cholesterol. Evidence: 10/10. Source: PMID 33980691. Slightly Higher.
Triglycerides. Evidence: 7/10. Source: PMID 33980691. Slightly Lower.
Neurology & Mental Health
Behavioral & Personality Traits
Physical Activity. Evidence: 6/10. Source: PMID 28448500. Slightly Lower.
Showing effects for A/A genotype
Body Mass Index. Evidence: 10/10. Source: PMID 20935630. Higher BMI.
Visceral Fat. Evidence: 7/10. Source: PMID 31501611. Higher Accumulation.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 30297969. ~1.1x Higher Risk.
Diastolic Blood Pressure. Evidence: 8/10. Source: PMID 33230300. Slightly Lower.
HDL Cholesterol. Evidence: 10/10. Source: PMID 33980691. Slightly Lower.
Triglycerides. Evidence: 7/10. Source: PMID 33980691. Slightly Higher.
Physical Activity. Evidence: 6/10. Source: PMID 28448500. Slightly Higher.
Showing effects for G/A genotype
Body Mass Index. Evidence: 10/10. Source: PMID 20935630. Typical BMI.
Visceral Fat. Evidence: 7/10. Source: PMID 31501611. Typical Accumulation.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 30297969. Typical Risk.
Diastolic Blood Pressure. Evidence: 8/10. Source: PMID 33230300. Typical.
HDL Cholesterol. Evidence: 10/10. Source: PMID 33980691. Typical.
Triglycerides. Evidence: 7/10. Source: PMID 33980691. Typical.
Physical Activity. Evidence: 6/10. Source: PMID 28448500. Typical.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
A highly favorable metabolic profile characterizes this genotype, which is linked to a lower body mass index and reduced risk of developing type 2 diabetes. Less visceral fat and lower overall body fat percentages are typical for this genetic makeup. Lipid profiles also tend to be healthier, showing lower circulating triglycerides and a lower triglyceride-to-HDL ratio. These metabolic benefits are accompanied by a tendency toward slightly higher diastolic blood pressure [1]. Additionally, studies have noted a minor association with lower self-reported physical activity levels [2]. Despite these minor trade-offs, the overall genetic influence points toward a lower risk of metabolic syndrome and related cardiovascular complications [3]. Adopting a balanced lifestyle can further enhance these natural metabolic advantages.
Lower predisposition to obesity; Reduced risk of type 2 diabetes; Slightly higher diastolic blood pressure.
Sample genotype: AA (Homozygous)
Elevated genetic predisposition for weight gain, higher body mass index, and type 2 diabetes characterizes this profile. Greater accumulation of visceral fat and higher overall body fat percentages are frequently observed. Less favorable lipid profiles, including higher triglycerides and a higher triglyceride-to-HDL ratio, are also common. Interestingly, this genotype is associated with higher self-reported physical activity levels, which may act as a natural compensatory mechanism [1]. Slightly lower diastolic blood pressure is another potential benefit, offering some cardiovascular protection [2]. Nevertheless, the dominant genetic signal points toward an increased risk of metabolic syndrome [3]. Proactive lifestyle habits, such as a balanced diet and regular exercise, are particularly important for managing these metabolic risks.
Higher predisposition to obesity; Increased risk of type 2 diabetes; Slightly lower diastolic blood pressure.
Sample genotype: GA (Heterozygous)
A balanced genetic influence places individuals with this heterozygous profile near the population average for most metabolic traits. No significantly elevated risk for high body mass index or type 2 diabetes is expected from this specific variant, as the single G allele helps mitigate the risk associated with the A allele. Similarly, diastolic blood pressure and lipid levels, including HDL cholesterol and triglycerides, tend to remain within typical ranges. While the A allele is linked to higher body fat and the G allele to higher blood pressure, having one of each generally results in intermediate, neutral effects. Maintaining a healthy lifestyle remains the primary driver of metabolic health for individuals with this genotype. Regular exercise and a balanced diet are highly effective in managing overall cardiovascular and metabolic wellness. Routine health screenings can help monitor these standard baseline levels over time.
Typical body mass index; Standard risk of type 2 diabetes; Average blood pressure levels.
Variants with shared genetic architecture
rs1128249 · COBLL1 Gene · Chr 2 · Metabolic Health Risk
rs1516725 · ETV5 Gene · Chr 3 · Weight and Body Fat
rs7132908 · FAIM2 Gene · Chr 12 · Obesity Risk
New genetic loci link adipose and insulin biology to body fat distribution.
Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.
Content updated August 2026.
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