Rs7903146

This SNP in TCF7L2 influences the risk of Type-2 diabetes (T2D). This SNP is also known as IVS3C>T.

[PMID 17671651] rs7903146(C;T) rs7903146(T;T) strongly predicted future type-2 diabetes. Considered in context with rs7903146 rs12255372 rs10885406.

Note: this is one of two SNPs within the TCF7L2 gene that have been reported to be associated with type-2 diabetes, the other being rs4506565. They have approximately equal power to estimate risk for type-2 diabetes, and the results from one correlate 92% of the time with the other. [PMID 17554300]

Full text of the paper is available from from Plos Medicine.

Or from NCBI as [PMID 17020404].

[PMID 16855264] TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program.

[PMID 17668382] reconfirmed in a diverse population

[PMID 17971425] Associated in a study of ~1000 Hispanic-Americans with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (p = 0.032).

[PMID 17671651] the CT/TT genotypes strongly predicted future type-2 diabetes. The risk T allele was associated with impaired insulin secretion, incretin effects, and enhanced rate of hepatic glucose production. TCF7L2 expression in human islets was increased 5-fold in T2D, particularly in carriers of the TT genotype.

This SNP is one of 4 relatively common SNPs reported to represent risk for type-2 diabetes in the DESIR prospective study of 3,877 Caucasian participants. Under an additive model, the odds ratio for the (T) risk allele is 1.45 (CI: 1.2-1.77, p=0.0002). For the 4 SNPs, each risk allele increased type-2 diabetes risk by 1.34x (p=2x10e-6), with an odds ratio of 2.48 (CI: 1.59-3.86) for carriers of 4 or more compared to those with one or none (risk alleles).[PMID 17977958]

Contrary to what's been seen in most populations studied so far, the association between rs7903146 and type-2 diabetes apparently does not hold in Arab populations, based on a case-control study of 522 Saudi patients and 346 controls.[PMID 18655717]

A HuGE review and meta-analysis including over 35,000 type-2 diabetes cases and 39,000 controls concluded that the Bayesian odds ratio for rs7903146(T;T) homozygotes and (C;T) heterozygotes versus (C;C) homozygotes was 1.968 (95% credible interval (CrI): 1.790 - 2.157) and 1.406 (95% CrI: 1.341 - 1.476), respectively, and the population attributable risk (PAR) for the (C;T)/(T;T) genotypes of this variant is 16.9% overall. Along with 3 other TCF7L2 SNPs, a multiplicative genetic model was indicated.[PMID 19228405]

A study of over 13,000 individuals initially free of cancer and followed over 10+ years found that the rs7903146(T) allele was associated with increased risk of colorectal cancer, with an adjusted odds ratio of 1.25 (CI:0.85-1.83) and 2.15 (CI:1.27-3.64) for the (C;T) and (T;T) genotypes, respectively.[PMID 18268068]

Does the association with type 2 diabetes hold for youth as well as for adults? Among African American youth, each copy of a rs7903146(T) allele was associated with a 1.97-fold (CI:1.37 - 2.82) increased odds for type 2 diabetes (p?<?0.0001), yet no significant association was detected in non-Hispanic white youth (adjusted odds ratio 1.14; CI: 0.73 - 1.79).[PMID 21109996]

[PMID 19258437] A Genetic Variant in the IGF2BP2 Gene may Interact with Fetal Malnutrition on Glucose Metabolism.

[PMID 18555673] The effect of WNT5B IVS3C>G on the susceptibility to type 2 diabetes in UK Caucasian subjects

GWAS snp
PMID	[PMID 19056611]
Trait	Type 2 diabetes
Title	Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome wide association data
Risk Allele
P-val	9E-30
Odds Ratio	1.49 [1.39-1.59]

GWAS snp
PMID	[PMID 18372903]
Trait	Type 2 diabetes
Title	Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
Risk Allele	T
P-val	3E-23
Odds Ratio	1.37 [1.28-1.47]

GWAS snp
PMID	[PMID 17463246]
Trait	Type 2 diabetes
Title	Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
Risk Allele	T
P-val	9.9999999999999997E-49
Odds Ratio	1.37 [1.31-1.43]

GWAS snp
PMID	[PMID 17463248]
Trait	Type 2 diabetes
Title	A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Risk Allele	T
P-val	9.9999999999999997E-49
Odds Ratio	1.37 [1.31-1.43]

GWAS snp
PMID	[PMID 17460697]
Trait	Type 2 diabetes
Title	A variant in CDKAL1 influences insulin response and risk of type 2 diabetes
Risk Allele
P-val	2.0000000000000001E-10
Odds Ratio	1.38 [NR]

GWAS snp
PMID	[PMID 17293876]
Trait	Type 2 diabetes
Title	A genome-wide association study identifies novel risk loci for type 2 diabetes
Risk Allele	T
P-val	1.9999999999999999E-34
Odds Ratio	1.65 [1.28, 2.02]

GWAS snp
PMID	[PMID 19401414]
Trait	Type 2 diabetes
Title	Confirmation of multiple risk loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population
Risk Allele	T
P-val	8E-12
Odds Ratio	1.54 [1.36-1.74]

[PMID 18972257] Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study--the HUNT study

[PMID 18996470] Rapid and cost effective genotyping method for polymorphisms in PPARG, PPARGC1 and TCF7L2 genes

[PMID 19473183] Interactions between TCF7L2 genotype and growth hormone-induced changes in glucose homeostasis in small for gestational age children

[PMID 19509102] Genetic Variants of TCF7L2 are Associated with Insulin Resistance and Related Metabolic Phenotypes in Taiwanese Adolescents and Caucasian Young Adults

[PMID 19533015] Transcription factor 7-like 2-gene polymorphism is related to fasting C peptide in latent autoimmune diabetes in adults (LADA)

[PMID 19183934] TCF7L2 variants are associated with increased proinsulin/insulin ratios but not obesity traits in the Framingham Heart Study

[PMID 19573884] No association between TCF7L2 rs7903146 and euglycemic-clamp-derived insulin sensitivity in a mixed-age cohort

[PMID 19585101] A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis

[PMID 19713311] TCF7L2 Polymorphism Associates with New-Onset Diabetes after Transplantation

GWAS snp
PMID	[PMID 19734900]
Trait	Type 2 diabetes and other traits
Title	Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia
Risk Allele	T
P-val	1E-30
Odds Ratio	1.48 [1.39-1.57]

[PMID 19864407] Effects of TCF7L2 polymorphisms on glucose values after a lifestyle intervention

[PMID 19924244] TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

[PMID 20028944] Gene variants of TCF7L2 influence weight loss and body composition during lifestyle intervention in a risk population for type 2 diabetes

[PMID 20041287] Polymorphisms of TCF7L2 and HHEX genes in Chinese women with polycystic ovary syndrome

[PMID 20043145] Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study

[PMID 20097709] Genotype and tissue-specific effects on alternative splicing of the transcription factor 7-like 2 gene in humans

[PMID 20437825] Relationship of five type 2 diabetes candidate gene polymorphisms to the age at diagnosis of diabetes in the Slovakian population

[PMID 20503258] Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City

[PMID 20546291] Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5)

[PMID 19806338] TCF7L2 genetic variants and progression to diabetes in the Chinese population: pleiotropic effects on insulin secretion and insulin resistance

[PMID 20578204] Transcription factor 7-like 2 (TCF7L2) polymorphism and context-specific risk of impaired fasting glucose in African American and Caucasian adults: the atherosclerosis risk in communities (ARIC) study

[PMID 20597906] A Validation Study of Type 2 Diabetes-related Variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ Genes in one Endogamous Ethnic Group of North India

GWAS snp
PMID	[PMID 20581827]
Trait	Type 2 diabetes
Title	Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
Risk Allele	T
P-val	2E-51
Odds Ratio	1.40 [1.34-1.46]

[PMID 20682688] Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: common genetic variants in GCK and TCF7L2 are associated with fasting and post-challenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes from the International Association of Diabetes and Pregnancy Study Groups

[PMID 20802253] Glycemia determines the effect of type 2 diabetes risk genes on insulin secretion

[PMID 20839289] Impact of repeated measures and sample selection on genome-wide association studies of fasting glucose

GWAS snp
PMID	[PMID 20694148]
Trait
Title	A genome-wide association study of the metabolic syndrome in Indian Asian men
Risk Allele	A
P-val	7E-7
Odds Ratio	1.33 [1.19-1.49]

GWAS snp
PMID	[PMID 20849430]
Trait
Title	The TCF7L2 Diabetes Risk Variant is Associated with HbA(1C) Levels: a Genome-Wide Association Meta-Analysis
Risk Allele	C
P-val	1E-7
Odds Ratio	0.05 [0.02-0.08] % HbA1C decrease

[PMID 20980453] Re-sequencing and Analysis of Variation in the TCF7L2 Gene in African Americans Suggests the SNP rs7903146 is the Causal Diabetes Susceptibility Variant

[PMID 21301999] Genetic variations in transcription factor 7-like 2 (TCF7L2) gene: association of TCF7L2 rs12255372(G/T) or rs7903146(C/T) with breast cancer risk and clinico-pathological parameters

[PMID 21414605] At-Risk Variant in TCF7L2 for Type II Diabetes Increases Risk of Schizophrenia

[PMID 21543200] Dietary saturated fat, gender and genetic variation at the TCF7L2 locus predict the development of metabolic syndrome

[PMID 21641671] Transcription factor 7-like 2 (TCF7L2) gene polymorphism and complication/comorbidity profile in type 2 diabetes patients

[PMID 21678030] Association of a common variant in TCF7L2 gene with type 2 diabetes mellitus in a Persian population

[PMID 22052079] Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs

[PMID 22109281] The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study

[PMID 21749608] Genetic variants and the metabolic syndrome: a systematic review

[PMID 22275441] Genetic risk assessment of type 2 diabetes-associated polymorphisms in african americans

GWAS snp
PMID	[PMID 22101970]
Trait
Title	Use of diverse electronic medical record systems to identify genetic risk for type 2 diabetes within a genome-wide association study.
Risk Allele	T
P-val	2E-15
Odds Ratio	1.4600 None

GWAS snp
PMID	[PMID 21873549]
Trait
Title	Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.
Risk Allele	T
P-val	2E-20
Odds Ratio	None None