rs7202877

badMag 4.5

This is a intergenic variant variant in the CTRB2 gene.

Key Literature Trait Associations

Type 1 Diabetes

The G allele at rs7202877 near CTRB1/CTRB2 on chromosome 16q23 is associated with increased risk of type 1 diabetes (OR 1.28, 95% CI 1.17-1.41) in a GWAS meta-analysis of over 7,500 T1D cases and 9,000 controls. The variant lies in an intergenic region between CTRB1 and CTRB2, which encode chymotrypsinogen B precursors expressed in pancreas; the G allele increases CTRB1/CTRB2 expression and chymotrypsin activity, potentially influencing pancreatic autoimmune processes.

Inshaw JRJ et al. “Analysis of overlapping genetic association in type 1 and type 2 diabetes.” Diabetologia 64(6):1342-1347 (2021)

Allele G

OR —

p —

N 915,815

Preliminary work

European

Barrett JC et al. “Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.” Nature Genetics 41(6):703-707 (2009)

Allele G

OR 1.28

p 3.1e-15

Meta-analysis

Adebekun J et al. “Genetic relations between type 1 diabetes, coronary artery disease and leukocyte counts.” Diabetologia (2024)

Allele G

OR —

p —

N 1,380,696

Preliminary work

multi-ancestry

Yazdanpanah N et al. “Clinically Relevant Circulating Protein Biomarkers for Type 1 Diabetes: Evidence From a Two-Sample Mendelian Randomization Study.” Diabetes Care (2022)

Allele G

OR 0.84

p 6.1e-6

N 25,427

Small GWAS

European

Type 2 Diabetes

The T allele at rs7202877 near BCAR1/CTRB1 is associated with increased susceptibility to type 2 diabetes (OR 1.12, 95% CI 1.07-1.16) in a meta-analysis of 34,840 cases and 114,981 controls of European ancestry. The T2D risk allele at this locus associates with decreased beta-cell function. Notably, the T1D and T2D risk alleles at this SNP are opposite (G for T1D, T for T2D), suggesting divergent pancreatic mechanisms.

't Hart LM et al. “The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway.” Diabetes (2013)

Allele T

OR —

β 0.055 ±0.012

p 4.0e-6

N 759

Small GWAS

European

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

Allele T

OR 1.12

p 3.5e-8

Large GWAS

Inshaw JRJ et al. “Analysis of overlapping genetic association in type 1 and type 2 diabetes.” Diabetologia 64(6):1342-1347 (2021)

Allele T

OR —

β 0.106 ±0.017

p 5.0e-10

N 898,130

Large GWAS

European

Harder MN et al. “Type 2 diabetes risk alleles near BCAR1 and in ANK1 associate with decreased β-cell function whereas risk alleles near ANKRD55 and GRB14 associate with decreased insulin sensitivity in the Danish Inter99 cohort.” The Journal of Clinical Endocrinology and Metabolism (2013)

Allele T

OR —

p 2.0e-2

N 8,495

Preliminary work

European

Sabiha B et al. “Assessment of genetic risk of type 2 diabetes among Pakistanis based on GWAS-implicated loci.” Gene (2021)

Allele T

OR —

p —

N 1,683

Preliminary work

South Asian

CPB1/KIRREL2 protein level ratio

rs7202877 is among the strongest genetic determinants of the CPB1/KIRREL2 plasma protein ratio (p=8×10⁻¹⁸⁴, beta=0.34), identified in a proteomics GWAS of 43,509 UK Biobank participants. This extraordinarily strong signal reflects the variant's role as a cis-pQTL for pancreatic exocrine enzyme expression in the CTRB1/BCAR1 locus region. The protein ratio approach used in this study was 7.6-fold enriched in known protein-protein interactions and identified this locus as a major hub for pancreatic protease regulation, reinforcing the mechanistic link between CTRB1/2 expression and diabetes susceptibility.

Suhre K et al. “Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions.” Cell Genomics (2024)

Allele G

OR —

β 0.340 ±0.012

p 8.0e-184

N 43,509

Large GWAS

European

Glycated hemoglobin levels

The G allele at rs7202877 is associated with altered HbA1c levels in a large GWAS of 363,228 UK Biobank individuals (PMID 33462484). This association is consistent with the variant's established role in modulating pancreatic exocrine function and incretin-mediated glycemic control via the CTRB1/2 pathway. The locus association with HbA1c is biologically plausible given that G-allele carriers show impaired DPP-4 inhibitor response and altered GLP-1 processing, resulting in suboptimal postprandial glucose regulation.

Sinnott-Armstrong N et al. “Genetics of 35 blood and urine biomarkers in the UK Biobank.” Nature Genetics 53(2):185-194 (2021)

Allele G

OR —

p —

N 363,228

Major Consortium Study

multi-ancestry

▶

GWAS Catalog Trait Associations (3)

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

type 1 diabetes mellitus

Barrett JC et al. “Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.” Nature Genetics 41(6):703-707 (2009)

Allele G

OR 1.28

p 3.0e-15

N 16,559

Meta-analysisLarge GWAS

European

type 2 diabetes mellitus

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 G

OR 0.11

p 5.0e-10

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 G

OR 1.12

p 4.0e-8

N 69,033

Large GWAS

multi-ancestry

HbA1c measurement

Sinnott-Armstrong N et al. “Genetics of 35 blood and urine biomarkers in the UK Biobank.” Nature Genetics 53(2):185-194 (2021)

Allele G

OR 0.03

p 7.0e-10

N 338,919

Major Consortium StudyLarge GWAS

multi-ancestry

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

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

Comments

Loading comments…