rs964184

badMag 4.5

This is a intergenic variant variant in the APOA5 gene.

Key Literature Trait Associations

Triglyceride Levels

The rs964184 G allele is robustly associated with higher fasting plasma triglycerides across multiple independent cohorts and ancestries. In a prospective vascular disease cohort (n=5,547), each minor allele copy increased log-triglycerides by β=0.12 (95% CI 0.10–0.15, p=1.1×10⁻¹⁹), with the effect amplified at higher BMI. Fine-mapping in Mexican-ancestry samples confirmed rs964184 as the sole variant in the 99% credible set at the BUD13/ZNF259/APOA5 locus, indicating it likely drives the ancestral signal. The G allele frequency is 30–40% higher in Native American populations than in Europeans, contributing to elevated TG prevalence in admixed Latin American groups. In HIV patients on antiretroviral therapy, the GG genotype was associated with an OR of 3.2 (95% CI 1.7–5.8) for hypertrig...

van de Woestijne AP et al. “Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease.” Plos One (2014)
Allele G
OR —
β 0.120
p 1.1e-19
N 5,547
Large GWAS
European
Teslovich TM et al. “Biological, clinical and population relevance of 95 loci for blood lipids.” Nature 466(7307):707-713 (2010)
Allele G
OR —
p 5.0e-8
N 100,184
Small GWAS
European
Bautista-Martínez JS et al. “Contribution of APOA5, APOC3, CETP, ABCA1 and SIK3 genetic variants to hypertriglyceridemia development in Mexican HIV-patients receiving antiretroviral therapy.” Pharmacogenetics and Genomics (2022)
Allele G
OR 3.20
p 1.0e-4
N 602
Preliminary work
Mexican mestizo
Parra EJ et al. “Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal.” Plos One (2017)
Allele G
OR —
p —
Candidate gene study
Mexican (Native American admixed)

HDL cholesterol

Beyond its primary effect on triglycerides, rs964184 G also influences HDL cholesterol through the APOA5/APOC3/APOA1 cluster, reflecting tight metabolic coupling between VLDL catabolism and HDL biogenesis. GWAS Catalog data from large-scale meta-analyses reports a genome-wide significant association with HDL-C (β=0.3 SD, p=4×10⁻⁶²). The relationship is physiologically plausible: APOA5 promotes lipoprotein lipase activity, and the HDL-TG/HDL-C ratio (atherogenic index) is co-regulated at this locus. The triglyceride-to-HDL ratio was also significantly altered in pediatric sickle cell disease patients carrying the G allele (p=0.032).

Teslovich TM et al. “Biological, clinical and population relevance of 95 loci for blood lipids.” Nature 466(7307):707-713 (2010)
Allele G
OR —
β 0.300
p 4.0e-62
N 100,184
Large GWAS
European
Valente-Frossard TNS et al. “Polymorphisms in genes that affect the variation of lipid levels in a Brazilian pediatric population with sickle cell disease: rs662799 APOA5 and rs964184 ZPR1.” Blood Cells, Molecules & Diseases (2020)
Allele G
OR —
p 3.2e-2
Candidate gene study
Brazilian (sickle cell disease)
▶

GWAS Catalog Trait Associations (488)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

cholesterol in chylomicrons and extremely large VLDL measurement

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.21
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.22
p 1.0e-200
N 88,329
Large GWAS
European

cholesterol in large HDL measurement

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.12
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.12
p 9.0e-76
N 88,329
Large GWAS
European

cholesterol in large VLDL measurement

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.19
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.21
p 1.0e-200
N 88,329
Large GWAS
European

cholesterol in very large HDL measurement

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.12
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.11
p 9.0e-70
N 88,329
Large GWAS
European

cholesterol in very large VLDL measurement

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.18
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.20
p 1.0e-197
N 88,329
Large GWAS
European

cholesterol to total lipids in large HDL percentage

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.17
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.17
p 9.0e-141
N 88,329
Large GWAS
European

cholesterol to total lipids in medium HDL percentage

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.20
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.19
p 3.0e-185
N 88,329
Large GWAS
European

cholesterol to total lipids in medium VLDL percentage

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.17
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.18
p 4.0e-156
N 88,329
Large GWAS
European

cholesterol to total lipids in small HDL percentage

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.19
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.17
p 2.0e-139
N 88,329
Large GWAS
European

cholesterol to total lipids in very large VLDL percentage

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele C
OR 0.15
p —
N 450,015
Large GWAS
multi-ancestry
Davyson E et al. “Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.” Biological Psychiatry 94(8):630-639 (2023)
Allele C
OR 0.15
p 5.0e-106
N 87,620
Large GWAS
European
▶

Research that mentions this SNP (4)

▶
Genetic variation of FTO: rs1421085 T&gt;C, rs8057044 G&gt;A, rs9939609 T&gt;A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight
ReviewLizbeth González‐Herrera et al.(2019)· American Journal of Human Biology

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

Traits studied:AdiposityBlood pressureBody mass index (BMI)Cardiovascular risk factorsDyslipidemiaInsulin resistanceMetabolic syndromeObesityOverweightType 2 diabetes
PubMedDOIMetascience Observatory
▶
Association of TGFBR2 rs6785358 Polymorphism with Increased Risk of Congenital Ventricular Septal Defect in a Chinese Population
AssociationN=3,000Xiang-Ting Li et al.(2015)· Pediatric Cardiology

This association study examined 141 tag SNPs in 8 transforming growth factor-beta (TGFβ) signaling pathway genes (SMAD2, SMAD3, SMAD4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2) in 3,000 Taiwanese subjects (2,467 without metabolic syndrome, 533 with) to assess associations with metabolic syndrome (MetS). The study found significant associations with SMAD2 rs11082639 (OR=1.66, 95% CI=1.32-2.08, P=1.4×10⁻⁵ in additive model) and TGFBR2 rs3773651 (OR=1.50, 95% CI=1.04-2.15, P=0.0285 in additive model), which remained significant after Bonferroni correction. SMAD2 rs11082639 was specifically associated with high waist circumference. Gene-gene interaction analysis revealed a significant interaction between SMAD2 and TGFBR2 variants influencing MetS risk.

Traits studied:blood pressurefasting glucosehigh-density lipoprotein cholesterolmetabolic syndrometriglyceridewaist circumference
PubMedDOIMetascience Observatory
▶
Investigation of genetic risk factors for chronic adult diseases for association with preterm birth
AssociationN=1,792Nadia Falah et al.(2013)· Human Genetics

Case-control study of 673 preterm birth (PTB) cases vs 1,119 controls across four maternal cohorts testing 35 SNPs in cardiovascular, inflammatory, and metabolic disease genes. Found 13 statistically significant associations with PTB (P<0.05), more than expected by chance (binomial P=0.02). Most significant was HLA-DQA1 rs9272346 G allele protective effect in US White mothers (P=0.02, OR=0.65, 95% CI 0.46-0.94), which nominally replicated in Danish cohort (P=0.02, OR=0.85, 95% CI 0.75-0.97) but lost significance after correction for multiple testing.

Traits studied:Cardiovascular diseaseHeight and weightHemostasis and thrombosisHypertensionInflammatory and immunological diseaseLipids and glucose metabolismMyocardial infarctionObesityPreterm birth
PubMedDOIMetascience Observatory
▶
Common genetic variants associated with lipid profiles in a Chinese pediatric population
AssociationN=3,503Yue Shen et al.(2013)· Human Genetics

This study tested seven SNPs from European lipid-associated loci in 3,503 Chinese school-age children and found that six SNPs (rs2144300, rs1260333, rs1260326, rs10105606, rs1748195, rs964184) showed significant associations with triglyceride levels (p < 0.05 FDR-corrected), while three SNPs were associated with total cholesterol and four with LDL-cholesterol. Three SNPs (rs1260333 OR=0.82, rs1260326 OR=0.82, rs964184 OR=1.36) showed strong associations with dyslipidemia risk, demonstrating that lipid-susceptibility variants identified in European populations have similar effects in Chinese children.

Traits studied:DyslipidemiaHDL-cholesterolLDL-cholesterolTotal cholesterolTriglycerides
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

No community notes yet for this variant. Sign in to start one.

Comments

Sign in to join the discussion.

Loading comments…