%0 Journal Article %1 Wittekind2021-pf %A Wittekind, Dirk Alexander %A Scholz, Markus %A Kratzsch, Jürgen %A Löffler, Markus %A Horn, Katrin %A Kirsten, Holger %A Witte, Veronica %A Villringer, Arno %A Kluge, Michael %D 2021 %I Bioscientifica %J Eur. J. Endocrinol. %K %N 6 %P 847--856 %T Genome-wide association and transcriptome analysis suggests total serum ghrelin to be linked with GFRAL %V 184 %X 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.

@article{Wittekind2021-pf, 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.}, added-at = {2024-09-10T11:56:37.000+0200}, author = {Wittekind, Dirk Alexander and Scholz, Markus and Kratzsch, J{\"u}rgen and L{\"o}ffler, Markus and Horn, Katrin and Kirsten, Holger and Witte, Veronica and Villringer, Arno and Kluge, Michael}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/27f0bf1c5ff5a4f2a777b628f752430b4/scadsfct}, interhash = {f785c6740b357b21f12b322903b808c6}, intrahash = {7f0bf1c5ff5a4f2a777b628f752430b4}, journal = {Eur. J. Endocrinol.}, keywords = {}, month = jun, number = 6, pages = {847--856}, publisher = {Bioscientifica}, timestamp = {2024-09-10T15:15:57.000+0200}, title = {Genome-wide association and transcriptome analysis suggests total serum ghrelin to be linked with {GFRAL}}, volume = 184, year = 2021 }