Dataset Information

Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk.

ABSTRACT:

Background

Observational studies have suggested that the gut hormone ghrelin is an early marker of future risk of developing gastrointestinal cancer. However, whether ghrelin is a causal risk factor remains unclear. We conducted a genome-wide association study (GWAS) of plasma ghrelin and used Mendelian randomization (MR) to investigate the possible causal association between ghrelin and gastrointestinal cancer risk.

Methods

Genetic variants associated with plasma ghrelin were identified in a GWAS comprising 10,742 Swedish adults in the discovery (N = 6,259) and replication (N = 4,483) cohorts. The association between ghrelin and gastrointestinal cancer was examined through a two-sample MR analysis using the identified genetic variants as instruments and GWAS data from the UK Biobank, FinnGen, and a colorectal cancer consortium.

Results

GWAS found associations between multiple genetic variants within ±200 kb of the GHRL gene and plasma ghrelin. A two-sample MR analysis revealed that genetically predicted higher plasma ghrelin levels were associated with a lower risk of gastrointestinal cancer in UK Biobank and in a meta-analysis of the UK Biobank and FinnGen studies. The combined OR per approximate doubling of genetically predicted plasma ghrelin was 0.91 (95% confidence interval, 0.85-0.99; P = 0.02). Colocalization analysis revealed limited evidence of shared causal variants for plasma ghrelin and gastrointestinal cancer at the GHRL locus (posterior probability H4 = 24.5%); however, this analysis was likely underpowered.

Conclusions

Our study provides evidence in support of a possible causal association between higher plasma ghrelin levels and a reduced risk of gastrointestinal cancer.

Impact

Elevated plasma ghrelin levels might reduce the risk of gastrointestinal cancer.

SUBMITTER: Larsson SC

PROVIDER: S-EPMC10690139 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk.

Larsson Susanna C SC Höijer Jonas J Sun Jing J Li Xue X Burgess Stephen S Michaëlsson Karl K

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20231201 12

<h4>Background</h4>Observational studies have suggested that the gut hormone ghrelin is an early marker of future risk of developing gastrointestinal cancer. However, whether ghrelin is a causal risk factor remains unclear. We conducted a genome-wide association study (GWAS) of plasma ghrelin and used Mendelian randomization (MR) to investigate the possible causal association between ghrelin and gastrointestinal cancer risk.<h4>Methods</h4>Genetic variants associated with plasma ghrelin were ide ...[more]

PMID: 37791980

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Dataset Information

Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk.

Background

Methods

Results

Conclusions

Impact

Publications

Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk.

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