rs4129267

This variant is located in the IL6R gene.

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GWAS Catalog Trait Associations (10)

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

interleukin-6 receptor subunit alpha measurement

Sun BB et al. “Genomic atlas of the human plasma proteome.” Nature 558(7708):73-79 (2018)

Allele T

OR 1.11

p —

N 3,301

Large GWAS

European

interleukin-6 measurement

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

Allele T

OR 0.21

p 2.0e-311

N 47,745

Large GWAS

European

interleukin 6 receptor subunit alpha measurement

Thareja G et al. “Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.” Human Molecular Genetics 32(6):907-916 (2023)

Allele T

OR 1.14

p 4.0e-303

N 2,935

Large GWAS

Greater Middle Eastern (Middle Eastern, North African or Persian)

Folkersen L et al. “Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease.” Plos Genetics 13(4):e1006706 (2017)

Allele T

OR 0.81

p 2.0e-297

N 3,394

Large GWAS

European

Suhre K et al. “Connecting genetic risk to disease end points through the human blood plasma proteome.” Nature Communications 8:14357 (2017)

Allele T

OR 1.21

p 2.0e-265

N 997

Small GWAS

multi-ancestry

Enroth S et al. “Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs.” Nature Communications 5:4684 (2014)

Allele T

OR 0.84

p 4.0e-58

N 970

Small GWAS

C-reactive protein measurement

Ligthart S et al. “Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.” American Journal of Human Genetics 103(5):691-706 (2018)

Allele C

OR 0.09

p 1.0e-129

N 206,158

Large GWAS

European

Dehghan A et al. “Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.” Circulation 123(7):731-8 (2011)

Allele C

OR 0.08

p 2.0e-48

N 66,185

Meta-analysisLarge GWAS

European

Jiang MZ et al. “Whole genome sequencing based analysis of inflammation biomarkers in the Trans-Omics for Precision Medicine (TOPMed) consortium.” Human Molecular Genetics 33(16):1429-1441 (2024)

Allele C

OR 0.08

p 8.0e-22

N 38,465

Major Consortium StudyLarge GWAS

multi-ancestry

Kocarnik JM et al. “Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study.” Human Molecular Genetics 27(16):2940-2953 (2018)

Allele C

OR 0.12

p 2.0e-26

N 30,503

Large GWAS

multi-ancestry

circulating fibrinogen levels

Sabater-Lleal M et al. “Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.” Circulation 128(12):1310-24 (2013)

Allele T

OR 0.01

p 6.0e-27

N 91,323

Meta-analysisLarge GWAS

multi-ancestry

mean corpuscular hemoglobin concentration

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 0.03

p 9.0e-23

N 583,865

Major Consortium StudyLarge GWAS

multi-ancestry

erythrocyte volume

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 0.03

p 2.0e-18

N 583,880

Major Consortium StudyLarge GWAS

multi-ancestry

asthma

Han Y et al. “Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma.” Nature Communications 11(1):1776 (2020)

Allele T

OR —

p 1.0e-17

N 536,345

Large GWAS

multi-ancestry

Ferreira MA et al. “Identification of IL6R and chromosome 11q13.5 as risk loci for asthma.” Lancet (london, England) 378(9795):1006-14 (2011)

Allele T

OR 1.09

p 2.0e-8

N 32,442

Large GWAS

European

Abdominal Aortic Aneurysm

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 0.10

p 6.0e-17

N 623,389

Major Consortium StudyLarge GWAS

multi-ancestry

ankylosing spondylitis

Cortes A et al. “Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci.” Nature Genetics 45(7):730-8 (2013)

Allele C

OR 1.18

p 2.0e-15

N 25,764

Large GWAS

multi-ancestry

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Research that mentions this SNP (2)

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Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B

AssociationN=6,033Jiang DK et al.(2015)· Hepatology

A genome-wide association study of 83 plasma proteins relevant to cardiovascular disease in 3,394 European subjects identified 79 genome-wide significant loci (p<5e-8), with 55 replicating in independent cohorts (n=2,639). Using eQTL analysis and network methods, the authors proposed plausible causal mechanisms for 25 trans-acting loci including post-translational regulation of KITLG by MMP9 and several receptor-ligand pairs. Multiple loci showed evidence of causal association with coronary artery disease risk.

Traits studied:AtherosclerosisCoronary artery diseasePlaque rupturePlasma protein levels (83 cardiovascular disease-related proteins)Thrombosis

PubMed DOI Metascience Observatory

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Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population

AssociationN=7,457Maarit Lappalainen et al.(2008)· Inflammatory Bowel Diseases

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.

Traits studied:Acute anterior uveitis (AAU)Ankylosing spondylitis (AS)Spondyloarthropathies

PubMed DOI Metascience Observatory

About IL6R

This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been identified in this gene. A pseudogene of this gene is found on chromosome 9. [provided by RefSeq, Aug 2020]

rs4129267

GWAS Catalog Trait Associations (10)

interleukin-6 receptor subunit alpha measurement

interleukin-6 measurement

interleukin 6 receptor subunit alpha measurement

C-reactive protein measurement

circulating fibrinogen levels

mean corpuscular hemoglobin concentration

erythrocyte volume

asthma

Abdominal Aortic Aneurysm

ankylosing spondylitis

Research that mentions this SNP (2)

About IL6R

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