„Identification of metabolic state-dependently methylated odorant receptor genes (FA2 module 3)“

Overweight is a major health problem that can be induced by eating behavior, which is driven by our chemical senses olfaction and taste. In a genome-wide linkage scan for the detection of alleles that were associated with eating behavior, it was shown that variations in human odorant receptor genes may influence eating behavior and obesity.1 Beside the occurrence of odorant receptor genes in the olfactory epithelium, numerous scientific publications also described their existence in peripheral tissues.2-6

So far, it is not known whether metabolic state-dependent, odorant receptor-specific, epigenetic variations, can serve as early molecular biomarkers for childhood overweight. However, in olfactory sensory neurons, both the mono-allelic expression of odorant receptor genes7,8 and an odorant receptor gene expression affected by environmental stimuli9,10 are epigenetically regulated. The relation between specific, epigenetic DNA methylation and peripheral hyperglycemia and diabetes was described for the odorant receptor OR10A4 in peripheral leukocytes of healthy adults.11 Moreover, two odorant receptor genes and one taste receptor gene with significant epigenetic variations were identified in human neutrophils of healthy individuals by genome-scale DNA methylome profiling.12,13 Furthermore, odorant receptor genes, identified e.g. by whole-genome methylation data on OR51B4, so far, may act as cancer-specific biomarkers.14

In this module of the enable-Focus Area 2, odorant receptor genes that are significantly different with respect to their DNA methylation patterns and transcript levels in leukocytes should be identified in overweight vs. normal-weight school-aged children. Moreover, the identified genes will be evaluated in cord blood from offspring of overweight mothers from the mother-child cohort PEACHES15 as potential risk predictors for later childhood overweight.


Our objectives:

  • Establishing methods to analyze DNA methylation patterns and gene transcript levels in peripheral blood leukocytes
  • Identification of significant differences in gene expression and/or epigenetic signatures of odorant receptor genes in leukocytes, in overweight vs. normal-weight school-aged children
  • Evaluation of identified odorant receptor genes in cord blood from offspring of overweight mothers from the mother-child cohort PEACHES



1              Choquette, A. C. et al. Association between olfactory receptor genes, eating behavior traits and adiposity: results from the Quebec Family Study. Physiology & behavior105, 772-776, doi:10.1016/j.physbeh.2011.10.015 (2012).
2              Feingold, E. A., Penny, L. A., Nienhuis, A. W. & Forget, B. G. An Olfactory Receptor Gene Is Located in the Extended Human β-Globin Gene Cluster and Is Expressed in Erythroid Cells. Genomics61, 15-23, doi:https://doi.org/10.1006/geno.1999.5935 (1999).
3              Babusyte, A., Kotthoff, M., Fiedler, J. & Krautwurst, D. Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2. Journal of Leukocyte Biology93, 387-394, doi:doi:10.1189/jlb.0912433 (2013).
4              Flegel, C., Manteniotis, S., Osthold, S., Hatt, H. & Gisselmann, G. Expression Profile of Ectopic Olfactory Receptors Determined by Deep Sequencing. PLOS ONE8, e55368, doi:10.1371/journal.pone.0055368 (2013).
5              Malki, A. et al. Class I odorant receptors, TAS1R and TAS2R taste receptors, are markers for subpopulations of circulating leukocytes. Journal of Leukocyte Biology97, 533-545, doi:10.1189/jlb.2A0714-331RR (2015).
6              Marcinek, P., Geithe, C. & Krautwurst, D. Chemosensory G Protein-Coupled Receptors (GPCR) in Blood Leukocytes. Top Med Chem Springer International Publishing Switzerland 2016, 1-23, doi:10.1007/7355_2016_101 (2016).
7              Monahan, K. & Lomvardas, S. Monoallelic Expression of Olfactory Receptors. Annual review of cell and developmental biology31, 721-740, doi:10.1146/annurev-cellbio-100814-125308 (2015).
8              Magklara, A. et al. An epigenetic signature for monoallelic olfactory receptor expression. Cell145, 555-570, doi:10.1016/j.cell.2011.03.040 (2011).
9              Dias, B. G. & Ressler, K. J. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature neuroscience17, 89-96, doi:10.1038/nn.3594 (2014).
10            Colquitt, B. M., Markenscoff-Papadimitriou, E., Duffie, R. & Lomvardas, S. Dnmt3a regulates global gene expression in olfactory sensory neurons and enables odorant-induced transcription. Neuron83, 823-838, doi:10.1016/j.neuron.2014.07.013 (2014).
11            Shim, S. M., Cho, Y. K., Hong, E. J., Han, B. G. & Jeon, J. P. An epigenomic signature of postprandial hyperglycemia in peripheral blood leukocytes. Journal of human genetics, doi:10.1038/jhg.2015.140 (2015).
12            Chatterjee, A. et al. Genome-wide DNA methylation map of human neutrophils reveals widespread inter-individual epigenetic variation. Scientific reports5, 17328, doi:10.1038/srep17328 (2015).
13            Chatterjee, A., Stockwell, P. A., Rodger, E. J. & Morison, I. M. Genome-scale DNA methylome and transcriptome profiling of human neutrophils. Scientific data3, 160019, doi:10.1038/sdata.2016.19 (2016).
14            Zhang, C. et al. The identification of specific methylation patterns across different cancers. PloS one10, e0120361, doi:10.1371/journal.pone.0120361 (2015).
15            Ensenauer, R. et al. Obese Nondiabetic Pregnancies and High Maternal Glycated Hemoglobin at Delivery as an Indicator of Offspring and Maternal Postpartum Risks: The Prospective PEACHES Mother-Child Cohort. Clinical Chemistry61, 1381, doi:10.1373/clinchem.2015.242206 (2015).