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  Genome-wide association and transcriptome analysis suggests total serum ghrelin to be linked with GFRAL

Wittekind, D. A., Scholz, M., Kratzsch, J., Löffler, M., Horn, K., Kirsten, H., et al. (2021). Genome-wide association and transcriptome analysis suggests total serum ghrelin to be linked with GFRAL. European Journal of Endocrinology, 184(6), 847-856. doi:10.1530/EJE-20-1220.

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Wittekind, Dirk Alexander1, Author
Scholz, Markus2, 3, Author
Kratzsch, Jürgen4, Author
Löffler, Markus2, 3, Author
Horn, Katrin2, 3, Author
Kirsten, Holger2, 3, Author
Witte, A. Veronica5, Author              
Villringer, Arno5, Author              
Kluge, Michael1, Author
Affiliations:
1Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Germany, ou_persistent22              
2Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Germany, ou_persistent22              
3Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Germany, ou_persistent22              
4Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics (ILM), University of Leipzig, Germany, ou_persistent22              
5Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634549              

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 Abstract: 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 and fall afterwards. Underlying genetic mechanisms of the ghrelin secretion are unknown. Methods: Total serum ghrelin was measured in 1501 subjects selected from the population-based LIFE-ADULT-sample after an overnight fast. A genome-wide association study (GWAS) was performed. Gene-based expression association analyses (transcriptome-wide association study (TWAS)) are statistical tests associating genetically predicted expression to a certain trait and were done using MetaXcan. Results: In the GWAS, three loci reached genome-wide significance: the WW-domain containing the oxidoreductase-gene (WWOX; P = 1.80E-10) on chromosome 16q23.3-24.1 (SNP: rs76823993); the contactin-associated protein-like 2 gene (CNTNAP2; P = 9.0E-9) on chromosome 7q35-q36 (SNP: rs192092592) and the ghrelin And obestatin prepropeptide gene (GHRL; P = 2.72E-8) on chromosome 3p25.3 (SNP: rs143729751). In the TWAS, the three genes where the expression was strongest associated with serum ghrelin levels was the ribosomal protein L36 (RPL36; P = 1.3E-06, FDR = 0.011, positively correlated), AP1B1 (P = 1.1E-5, FDR = 0.048, negatively correlated) and the GDNF family receptor alpha like (GFRAL), receptor of the anorexigenic growth differentiation factor-15 (GDF15), (P = 1.8E-05, FDR = 0.15, also negatively correlated). Conclusions: The three genome-wide significant genetic loci from the GWA and the genes identified in the TWA are functionally plausible and should initiate further research.

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Language(s): eng - English
 Dates: 2021-05-10
 Publication Status: Published online
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1530/EJE-20-1220
PMID: 33852427
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Title: European Journal of Endocrinology
  Other : Eur. J. Endocrinol.
Source Genre: Journal
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Publ. Info: Oslo, Norway : Scandinavian University Press
Pages: - Volume / Issue: 184 (6) Sequence Number: - Start / End Page: 847 - 856 Identifier: ISSN: 0804-4643
CoNE: https://pure.mpg.de/cone/journals/resource/954927511422