2020/09/24 by Dirk Alexander Wittekind, Markus Scholz, Wittekind, Dirk Alexander +15
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #FOS: Biological sciences #GDF15 and Related Biomarkers #Genetics and Neurodevelopmental Disorders #Genomics (q-bio.GN) #Nuclear Receptors and Signaling #RNA regulation and disease
paper · pdf · doi:10.48550/arxiv.2009.11549
openalex publication_date 2020/09/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Objective: Ghrelin is an orexigenic peptide hormone involved in the\nregulation of energy homeostasis, food intake and glucose metabolism. Serum\nlevels increase anticipating a meal and fall afterwards. Underlying genetic\nmechanisms of the ghrelin secretion are unknown. Methods: Total serum ghrelin\nwas measured in 1501 subjects selected from the population-based\nLIFE-ADULT-sample after an overnight fast. A genome-wide association study\n(GWAS) was performed. Gene-based expression association analyses\n(transcriptome-wide association study (TWAS)) were done using MetaXcan.\nResults: In the GWAS, three loci reached genome-wide significance: the\nWW-domain containing the oxidoreductase-gene (WWOX; p=1.80E-10) on chromosome\n16q23.3-24.1 (SNP: rs76823993); the Contactin-Associated Protein-Like 2 gene\n(CNTNAP2; p=9.0E-9) on chromosome 7q35-q36 (SNP: rs192092592) and the Ghrelin\nAnd Obestatin Prepropeptide gene (GHRL; p=2.72E-8) on chromosome 3p25.3 (SNP:\nrs143729751). In the TWAS, serum ghrelin was negatively associated with RNA\nexpression of the GDNF Family Receptor Alpha Like (GFRAL), receptor of the\nanorexigenic Growth Differentiation Factor-15 (GDF15), (z-score=-4.288,\np=1.81E-05). Furthermore, ghrelin was positively associated with Ribosomal\nProtein L36 (RPL36; z-score=4.848, p=1.25E-06). Conclusions: Our findings\nprovide evidence of a functional link between two major players of weight\nregulation, the ghrelin system and the GDF15/GFRAL-pathway.\n