| Title: | Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk |
| Journal: | Cancer Epidemiology Biomarkers & Prevention |
| Published: | 4 Oct 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37791980/ |
| DOI: | https://doi.org/10.1158/1055-9965.epi-23-0757 |
| URL: | https://aacrjournals.org/cebp/article-pdf/doi/10.1158/1055-9965.EPI-23-0757/3370638/epi-23-0757.pdf |
Publication 9426
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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.</p>
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.</p>
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.</p>
CONCLUSIONS: Our study provides evidence in support of a possible causal association between higher plasma ghrelin levels and a reduced risk of gastrointestinal cancer.</p>
IMPACT: Elevated plasma ghrelin levels might reduce the risk of gastrointestinal cancer.</p>
6 Authors
- Susanna C. Larsson
- Jonas Höijer
- Jing Sun
- Xue Li
- Stephen Burgess
- Karl Michaëlsson
1 Application
| Application ID | Title |
|---|---|
| 29202 | Epidemiologic and genetic analyses of aging-associated diseases and mortality |
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