Genome-wide association and transcriptome analysis reveals serum ghrelin to be linked with GFRAL.

作者: Arno Villringer , Dirk Alexander Wittekind , Markus Löffler , Holger Kirsten , Jürgen Kratzsch

DOI:

关键词: WWOXGhrelin secretionGhrelinBiologyOrexigenicObestatinEnergy homeostasisEndocrinologyInternal medicinePopulationGenome-wide association study

摘要: Objective: Ghrelin is an orexigenic peptide hormone involved in the regulation of energy homeostasis, food intake and glucose metabolism. Serum levels increase anticipating a meal fall afterwards. Underlying genetic mechanisms ghrelin secretion are unknown. Methods: Total serum was measured 1501 subjects selected from population-based LIFE-ADULT-sample after overnight fast. A genome-wide association study (GWAS) performed. Gene-based expression analyses (transcriptome-wide (TWAS)) were done using MetaXcan. Results: In GWAS, three loci reached significance: WW-domain containing oxidoreductase-gene (WWOX; p=1.80E-10) on chromosome 16q23.3-24.1 (SNP: rs76823993); Contactin-Associated Protein-Like 2 gene (CNTNAP2; p=9.0E-9) 7q35-q36 rs192092592) And Obestatin Prepropeptide (GHRL; p=2.72E-8) 3p25.3 rs143729751). TWAS, negatively associated with RNA GDNF Family Receptor Alpha Like (GFRAL), receptor anorexigenic Growth Differentiation Factor-15 (GDF15), (z-score=-4.288, p=1.81E-05). Furthermore, positively Ribosomal Protein L36 (RPL36; z-score=4.848, p=1.25E-06). Conclusions: Our findings provide evidence functional link between two major players weight regulation, system GDF15/GFRAL-pathway.

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