rs11708067

This is a intron variant variant in the ADCY5 gene.

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GWAS Catalog Trait Associations (40)

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

HbA1c measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele G

OR 0.05

p 1.0e-118

N 394,642

Large GWAS

European

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)

Allele G

OR 0.05

p 7.0e-56

N 338,640

Major Consortium StudyLarge GWAS

European

Wheeler E et al. “Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.” Plos Medicine 14(9):e1002383 (2017)

Allele G

OR 0.01

p 1.0e-12

N 88,355

Meta-analysisLarge GWAS

European

type 2 diabetes mellitus

Suzuki K et al. “Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.” Nature 627(8003):347-357 (2024)

Allele A

OR —

p 2.0e-92

N 2,535,601

Large GWAS

multi-ancestry

Elashi AA et al. “Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus.” Bmc Medical Genomics 17(1):115 (2024)

Allele A

OR 0.10

p 1.0e-42

N 6,710,881

Meta-analysisLarge GWAS

multi-ancestry

Vujkovic M et al. “Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.” Nature Genetics 52(7):680-691 (2020)

Allele A

OR 0.08

p 2.0e-57

N 1,407,282

Meta-analysisLarge GWAS

multi-ancestry

Mahajan A et al. “Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.” Nature Genetics 50(11):1505-1513 (2018)

Allele A

OR 1.09

p 5.0e-32

N 898,130

Large GWAS

European

Xue A et al. “Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.” Nature Communications 9(1):2941 (2018)

Allele A

OR 0.10

p 6.0e-29

N 659,316

Large GWAS

multi-ancestry

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)

Allele A

OR 0.06

p 3.0e-40

N 432,648

Major Consortium StudyLarge GWAS

European

Huerta-Chagoya A et al. “Rare variant analyses in 51,256 type 2 diabetes cases and 370,487 controls reveal the pathogenicity spectrum of monogenic diabetes genes.” Nature Genetics 56(11):2370-2379 (2024)

Allele A

OR 0.14

p 2.0e-53

N 421,743

Large GWAS

multi-ancestry

Zhao W et al. “Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.” Nature Genetics 49(10):1450-1457 (2017)

Allele A

OR 0.10

p 5.0e-20

N 183,651

Large GWAS

multi-ancestry

Morris AP et al. “Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes” Nature Genetics (2012)

Allele A

OR 1.13

p 2.0e-10

N 69,033

Large GWAS

multi-ancestry

Mahajan A et al. “Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.” Nature Genetics 54(5):560-572 (2022)

Allele A

OR 0.12

p 4.0e-8

N 27,417

Large GWAS

Hispanic or Latin American

hemoglobin A1 measurement

Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)

Allele G

OR 0.05

p 1.0e-85

N 415,403

Large GWAS

multi-ancestry

glucose measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele G

OR 0.05

p 1.0e-81

N 394,642

Large GWAS

European

Lagou V et al. “GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.” Nature Genetics 55(9):1448-1461 (2023)

Allele G

OR 0.01

p 2.0e-80

N 475,416

Large GWAS

multi-ancestry

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)

Allele G

OR 0.05

p 1.0e-80

N 450,015

Large GWAS

multi-ancestry

Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)

Allele G

OR 0.05

p 8.0e-70

N 448,252

Large GWAS

multi-ancestry

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)

Allele G

OR 0.08

p 7.0e-36

N 118,233

Major Consortium StudyLarge GWAS

African American or Afro-Caribbean

Chen J et al. “The trans-ancestral genomic architecture of glycemic traits.” Nature Genetics 53(6):840-860 (2021)

Allele G

OR —

β 0.032

p 1.0e-8

N 19,247

Large GWAS

Hispanic or Latin American

body height

Yengo L et al. “A saturated map of common genetic variants associated with human height.” Nature 610(7933):704-712 (2022)

Allele G

OR 0.01

p 2.0e-80

N 5,314,291

Large GWAS

European, Hispanic or Latin American, East Asian, African unspecified, South Asian

blood glucose amount

Jee YH et al. “Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures.” Nature Communications 16(1):4935 (2025)

Allele A

OR 0.05

p 7.0e-75

N 928,679

Large GWAS

multi-ancestry

Lagou V et al. “Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.” Nature Communications 12(1):24 (2021)

Allele A

OR 0.02

p 5.0e-22

N 140,595

Large GWAS

European

Wessel J et al. “Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.” Nature Communications 6:5897 (2015)

Allele A

OR 0.03

p 4.0e-16

N 60,564

Large GWAS

multi-ancestry

Manning AK et al. “A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.” Nature Genetics 44(6):659-69 (2012)

Allele A

OR 0.02

p 7.0e-9

N 58,074

Large GWAS

European

Dupuis J et al. “New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.” Nature Genetics 42(2):105-116 (2010)

Allele A

OR 0.03

p 7.0e-22

N 46,186

Large GWAS

European

alanine measurement

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)

Allele G

OR 0.04

p 6.0e-60

N 450,015

Large GWAS

multi-ancestry

Abar L et al. “Unravelling genetic architecture of circulatory amino acid levels, and their effect on risk of complex disorders.” Nar Genomics and Bioinformatics 6(2):lqae046 (2024)

Allele G

OR 0.03

p 1.0e-9

N 117,944

Large GWAS

European

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 G

OR 0.03

p 1.0e-12

N 88,325

Large GWAS

European

birth weight

Warrington NM et al. “Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.” Nature Genetics 51(5):804-814 (2019)

Allele G

OR 0.04

p 2.0e-42

N 321,223

Large GWAS

multi-ancestry

Plotnikov D et al. “Association between birth weight and refractive error in adulthood: a Mendelian randomisation study.” The British Journal of Ophthalmology 104(2):214-219 (2020)

Allele G

OR 0.04

p 6.0e-24

N 188,039

Large GWAS

European

Yang XL et al. “Three Novel Loci for Infant Head Circumference Identified by a Joint Association Analysis.” Frontiers in Genetics 10:947 (2019)

Allele G

OR 0.05

p 4.0e-25

N 182,902

Large GWAS

European

glucose tolerance test

Chen J et al. “The trans-ancestral genomic architecture of glycemic traits.” Nature Genetics 53(6):840-860 (2021)

Allele A

OR —

β 0.087

p 2.0e-22

N 63,396

Large GWAS

European

body height at birth

Yang XL et al. “Three Novel Loci for Infant Head Circumference Identified by a Joint Association Analysis.” Frontiers in Genetics 10:947 (2019)

Allele A

OR 0.06

p 9.0e-20

N 182,902

Large GWAS

European

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Research that mentions this SNP (5)

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Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium

AssociationN=26,760Stephanie A. Bien et al.(2017)· Diabetologia

Transethnic fine-mapping study of glycaemic traits in 26,760 participants (Hispanic/Latino, African, Asian, and Native American) using the Metabochip. Replicated 31/39 fasting glucose and 14/17 fasting insulin loci from European GWAS. Identified two novel secondary signals at G6PC2-rs477224 and GCK-rs2908290, a population-specific signal at G6PC2-rs77719485 in African ancestry, and one novel locus at SLC17A2-rs75862513 for fasting insulin.

Traits studied:Fasting glucoseFasting insulinType 2 diabetes

PubMed DOI Metascience Observatory

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PROX1 Gene Variant is Associated with Fasting Glucose Change After Antihypertensive Treatment

AssociationN=456Yan Gong et al.(2014)· Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

A pharmacogenomics study of 456 hypertensive participants examining whether fasting glucose GWAS variants predict glucose response to antihypertensive medications. The primary finding was that PROX1 rs340874 (C allele) was significantly associated with greater glucose elevation after 9 weeks of atenolol monotherapy (p=0.0013, beta = +2.39 mg/dL per allele). Two additional SNPs showed nominal associations: ARAP1 rs11603334 with atenolol response and SLC2A2 rs11920090 with HCTZ response.

Traits studied:Atenolol-induced hyperglycemiaFasting glucoseGlucose response to antihypertensive drugsHydrochlorothiazide-induced hyperglycemiaHypertension

PubMed DOI Metascience Observatory

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Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets

AssociationN=84Dayeh TA et al.(2013)· Diabetologia

Of 40 SNPs previously associated with type 2 diabetes, 19 (48%) introduce or remove CpG sites. In 84 human pancreatic islet donors, all 16 analyzed CpG-SNPs showed statistically significant differential DNA methylation (p≤2.3×10⁻⁵). Several CpG-SNPs including rs391300 (SRR), rs5945326 (DUSP9), rs11708067 (ADCY5), rs5015480 (HHEX), rs13266634 (SLC30A8), rs1801214 (WFS1), rs564398 (CDKN2A), and rs2237895 (KCNQ1) were associated with differential gene expression, alternative splicing, or hormone secretion, suggesting DNA methylation-mediated mechanisms linking genetic variants to type 2 diabetes pathogenesis.

Traits studied:Glucagon secretionInsulin contentInsulin secretionType 2 diabetes

PubMed DOI Metascience Observatory

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Association of glycosylated hemoglobin with the gene encoding CDKAL1 in the Korean Association Resource (KARE) study

Meta-analysisN=159,940Jihye Ryu et al.(2012)· Human Mutation

Transethnic genome-wide meta-analysis in 159,940 individuals identified 60 common genetic variants associated with HbA1c levels. Variants were classified as glycemic (19), erythrocytic (22), or unclassified (19) based on their biological mechanisms. Glycemic variants were associated with higher type 2 diabetes risk (OR=1.05 per allele, p=3×10⁻²⁹), while erythrocytic variants were not. The X-linked G6PD G202A variant showed a large effect in African Americans (0.81% HbA1c reduction per allele) but minimal effects in other ancestries, potentially causing 2% of African American T2D cases to remain undiagnosed when using HbA1c screening.

Traits studied:2-hour glucoseErythrocytic traitsFasting glucoseGlycemic traitsHemoglobin A1c (HbA1c)Type 2 diabetes

PubMed DOI Metascience Observatory

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Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight

AssociationN=4,213Andersson EA et al.(2010)· Diabetologia

This association study of 4,213 Danish individuals examined 25 type 2 diabetes risk variants and their association with birthweight. The study found that type 2 diabetes risk alleles near ADCY5 (rs11708067, β = -33 g, p = 0.004), CDKAL1 (rs7756992, β = -22 g, p = 0.04), and HHEX-IDE (rs1111875, β = -16 g in meta-analysis, p = 8×10⁻⁵, n = 25,164) were associated with reduced birthweight, supporting the fetal insulin hypothesis. Meta-analyses confirmed these associations and showed no strong general effect on birthweight from the 25 common type 2 diabetes risk alleles combined.

Traits studied:Birth lengthBirthweightPonderal indexType 2 diabetes

PubMed DOI Metascience Observatory

About ADCY5

This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

rs11708067

GWAS Catalog Trait Associations (40)

HbA1c measurement

type 2 diabetes mellitus

hemoglobin A1 measurement

glucose measurement

body height

blood glucose amount

alanine measurement

birth weight

glucose tolerance test

body height at birth

Research that mentions this SNP (5)

About ADCY5

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