rs2237897

This is a regulatory region variant variant in the KCNQ1 gene.

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GWAS Catalog Trait Associations (16)

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

type 2 diabetes mellitus

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

Allele C

OR —

p —

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 C

OR 0.24

p 9.0e-191

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 C

OR 0.22

p 2.0e-226

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 C

OR 1.23

p 8.0e-32

N 898,130

Large GWAS

European

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

Allele C

OR 0.27

p 1.0e-196

N 667,504

Large GWAS

multi-ancestry

Spracklen CN et al. “Identification of type 2 diabetes loci in 433,540 East Asian individuals.” Nature 582(7811):240-245 (2020)

Allele C

OR 1.28

p 2.0e-245

N 433,540

Large GWAS

East Asian

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 C

OR 0.30

p 8.0e-53

N 421,743

Large GWAS

multi-ancestry

Ishigaki K et al. “Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.” Nature Genetics 52(7):669-679 (2020)

Allele C

OR 0.79

p 3.0e-168

N 210,865

Large GWAS

East Asian

Suzuki K et al. “Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.” Nature Genetics 51(3):379-386 (2019)

Allele C

OR 1.30

p 3.0e-168

N 191,764

Large GWAS

East Asian

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 C

OR 0.16

p 2.0e-24

N 116,014

Major Consortium StudyLarge GWAS

African American or Afro-Caribbean

Walters RG et al. “Genotyping and population characteristics of the China Kadoorie Biobank.” Cell Genomics 3(8):100361 (2023)

Allele C

OR 0.82

p 1.0e-14

N 77,178

Large GWAS

East Asian

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 C

OR 0.21

p 5.0e-39

N 27,417

Large GWAS

Hispanic or Latin American

Williams AL et al. “Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico.” Nature 506(7486):97-101 (2014)

Allele C

OR 1.31

p 9.0e-15

N 8,214

Large GWAS

multi-ancestry

Unoki H et al. “SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations.” Nature Genetics 40(9):1098-102 (2008)

Allele C

OR 1.33

p 1.0e-16

N 1,752

Large GWAS

multi-ancestry

Drugs used in diabetes use measurement

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

Allele T

OR 0.25

p 2.0e-127

N 178,726

Large GWAS

East Asian

body weight

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

Allele T

OR 0.04

p 2.0e-45

N 525,535

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 T

OR 0.04

p 6.0e-12

N 609,198

Major Consortium StudyLarge GWAS

multi-ancestry

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 T

OR 0.06

p 3.0e-40

N 71,221

Large GWAS

East Asian

body mass index

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 T

OR 0.03

p 5.0e-38

N 928,679

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 T

OR 0.04

p 9.0e-37

N 523,818

Large GWAS

multi-ancestry

Akiyama M et al. “Genome-wide association study identifies 112 new loci for body mass index in the Japanese population.” Nature Genetics 49(10):1458-1467 (2017)

Allele T

OR 0.04

p 1.0e-30

N 158,284

Large GWAS

multi-ancestry

Gong J et al. “Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI.” International Journal of Obesity (2005) 42(3):384-390 (2018)

Allele T

OR —

β 0.007

p 2.0e-8

N 102,514

Large GWAS

multi-ancestry

diabetic retinopathy

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 C

OR 0.19

p 1.0e-32

N 611,288

Major Consortium StudyLarge GWAS

multi-ancestry

diabetes mellitus, Drugs used in diabetes use measurement

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 C

OR 0.16

p 2.0e-31

N 404,034

Major Consortium StudyLarge GWAS

multi-ancestry

insulin measurement

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 C

OR 0.19

p 2.0e-13

N 619,297

Major Consortium StudyLarge GWAS

multi-ancestry

gestational diabetes

Pujol Gualdo N et al. “Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.” Nature Medicine 31(5):1626-1634 (2025)

Allele C

OR 1.18

p 2.0e-9

N 300,553

Large GWAS

European

blood glucose amount

Allele T

OR 0.06

p 1.0e-56

N 153,950

Large GWAS

East Asian

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Research that mentions this SNP (3)

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KCNQ1 SNPS and susceptibility to diabetic nephropathy in East Asians with type 2 diabetes

AssociationN=752Lim XL et al.(2012)· Diabetologia

This study investigated three KCNQ1 SNPs (rs2237895, rs2237897, rs2283228) for association with diabetic nephropathy in 752 Chinese type 2 diabetic patients. rs2283228 showed significant association with macroalbuminuria (p<0.001, OR 6.00, 95% CI 2.68-13.41 under recessive model) and log albumin/creatinine ratio (p=0.004). Meta-analysis combining Chinese and Japanese populations confirmed both rs2283228 and rs2237897 were significantly associated with macroalbuminuria, supporting KCNQ1 as a susceptibility locus for diabetic nephropathy in East Asians.

Traits studied:AlbuminuriaDiabetic nephropathyMacroalbuminuriaMicroalbuminuriaType 2 diabetes

PubMed DOI Metascience Observatory

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Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population

AssociationN=3,503Hu C. et al.(2009)· Diabetologia

This case-control study validates the association between KCNQ1 variants and type 2 diabetes in a Chinese population of 3,503 individuals. All four tested SNPs (rs2074196, rs2237892, rs2237895, rs2237897) were significantly associated with type 2 diabetes, with rs2237892 showing the strongest association (OR 1.532, 95% CI 1.381-1.698, p=5.0×10^-16). The variants appear to influence disease susceptibility through effects on pancreatic beta cell function, as evidenced by associations with insulin secretion measures.

Traits studied:Acute C-peptide responseAcute insulin responseBeta cell functionFirst-phase insulin secretionSecond-phase insulin secretionType 2 diabetes

PubMed DOI Metascience Observatory

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Variants in KCNQ1 are associated with susceptibility to type 2 diabetes in the population of mainland China

AssociationN=3,953Liu Y. et al.(2009)· Diabetologia

This case-control association study in mainland China (1,912 type 2 diabetes cases, 2,041 controls) examined three KCNQ1 variants previously identified by genome-wide association studies. All three variants (rs2237892, rs2237895, rs2237897) showed significant association with type 2 diabetes risk: rs2237892 (OR 1.23, p=1.1×10⁻⁴), rs2237895 (OR 1.23, p=7.8×10⁻⁵), and rs2237897 (OR 1.28, p=2.0×10⁻⁶). These variants were also associated with BMI, waist measurements, and glycemic traits, confirming previous findings in Asian and European populations.

Traits studied:Body mass index (BMI)Fasting plasma glucoseHbA1c levelsType 2 diabetesWaist measurement

PubMed DOI Metascience Observatory

About KCNQ1

This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

rs2237897

GWAS Catalog Trait Associations (16)

type 2 diabetes mellitus

Drugs used in diabetes use measurement

body weight

hemoglobin A1 measurement

body mass index

diabetic retinopathy

diabetes mellitus, Drugs used in diabetes use measurement

insulin measurement

gestational diabetes

blood glucose amount

Research that mentions this SNP (3)

About KCNQ1

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