Making sense out of GWAS findings – starting from the individual The genetic overlap between major depression and body mass index

• Applicant: Dr. Sandra van der Auwera
• Subject Area: Biological Psychiatry ; Epidemiology and Medical Biometry/Statistics
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 403694598

• Final Report Year: 2023

Final Report Abstract

Depression and obesity are two diseases whose frequency has increased significantly in recent years. In many cases, people are affected by both complaints at the same time. In addition to environmental influences and unfavorable lifestyle, genetic factors also play a role. Large population studies have already been able to identify genes and biological pathways that increase the respective risk of the disease. Some of these genetic risk factors for both conditions overlap. However, it is still unclear whether these are also relevant for the comorbidity and how they act biologically. The aim of this project was therefore, based on the already identified genetic risk factors for depression and high BMI, to identify those genetic variants that increase the risk of obesity in depressed people or the risk of depression in obese people. Finding such genetic markers can help to better understand the biological processes underlying this comorbidity, identify people at risk for developing the comorbidity and to improve treatment methods. The so-called "OTTO approach" that we used here starts with individuals who have a special genetic and/or phenotypic profile and tries to find risk factors for the comorbidity based on this. During the course of the project, it turned out that this approach was not successful in identifying replicable genetic risk factors that increase the likelihood of comorbidity. This is probably due to the high genotypic and phenotypic heterogeneity of both diseases and the strong environmental influences.

Publications

• The association between genetically determined ABO blood types and major depressive disorder. Psychiatry Research, 299, 113837.
  Garvert, Linda; Baune, Bernhard T.; Berger, Klaus; Boomsma, Dorret I.; Breen, Gerome; Greinacher, Andreas; Hamilton, Steven P.; Levinson, Douglas F.; Lewis, Cathryn M.; Lucae, Susanne; Magnusson, Patrik K. E.; Martin, Nicholas G.; McIntosh, Andrew M.; Mors, Ole; Müller-Myhsok, Bertram; Penninx, Brenda W. J. H.; Perlis, Roy H.; Pistis, Giorgio; Potash, James B. ... & Van, der Auwera Sandra
  
• The genetic predisposition to longevity acts through behavioral phenotypes in females. European Neuropsychopharmacology, 45, 1-14.
  Van der Auwera, Sandra; Garvert, Linda; Fuellen, Georg; Nauck, Matthias; Völzke, Henry; Völker, Uwe & Grabe, Hans J.
  
• APOE ε4 in Depression-Associated Memory Impairment—Evidence from Genetic and MicroRNA Analyses. Biomedicines, 10(7), 1560.
  Bonk, Sarah; Kirchner, Kevin; Ameling, Sabine; Garvert, Linda; Völzke, Henry; Nauck, Matthias; Völker, Uwe; Grabe, Hans J. & Van, der Auwera Sandra
  
• Genome-wide gene-gene interaction of the 5-HTTLPR promoter polymorphism emphasizes the important role of neuroplasticity in depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 119, 110614.
  Garvert, Linda; Kirchner, Kevin; Grabe, Hans J. & Van der Auwera, Sandra
  
• The relationship between Alzheimer's‐related brain atrophy patterns and sleep macro‐architecture. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 14(1).
  Weihs, Antoine; Frenzel, Stefan; Garvert, Linda; Kühn, Luise; Wittfeld, Katharina; Ewert, Ralf; Fietze, Ingo; Penzel, Thomas; Stubbe, Beate; Szentkirályi, András; Wulms, Niklas; Völzke, Henry & Grabe, Hans J.
  
• TREML2 Gene Expression and Its Missense Variant rs3747742 Associate with White Matter Hyperintensity Volume and Alzheimer’s Disease-Related Brain Atrophy in the General Population. International Journal of Molecular Sciences, 23(22), 13764.
  Kühn, Annemarie Luise; Frenzel, Stefan; Teumer, Alexander; Wittfeld, Katharina; Garvert, Linda; Weihs, Antoine; Homuth, Georg; Prokisch, Holger; Bülow, Robin; Nauck, Matthias; Völker, Uwe; Völzke, Henry; Grabe, Hans Jörgen & Van, der Auwera Sandra
  
• Vitamin D deficit is associated with accelerated brain aging in the general population. Psychiatry Research: Neuroimaging, 327, 111558.
  Terock, Jan; Bonk, Sarah; Frenzel, Stefan; Wittfeld, Katharina; Garvert, Linda; Hosten, Norbert; Nauck, Matthias; Völzke, Henry; Van der Auwera, Sandra & Grabe, Hans Joergen
  
• Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population. International Journal of Molecular Sciences, 24(2), 1120.
  Kirchner, Kevin; Garvert, Linda; Wittfeld, Katharina; Ameling, Sabine; Bülow, Robin; Meyer, zu Schwabedissen Henriette; Nauck, Matthias; Völzke, Henry; Grabe, Hans J. & Van, der Auwera Sandra
  
• Depression, cardiometabolic disease, and their co-occurrence after childhood maltreatment: an individual participant data meta-analysis including over 200,000 participants. BMC Medicine, 21(1).
  Souama, Camille; Lamers, Femke; Milaneschi, Yuri; Vinkers, Christiaan H.; Defina, Serena; Garvert, Linda; Stein, Frederike; Woofenden, Tom; Brosch, Katharina; Dannlowski, Udo; Galenkamp, Henrike; de Graaf, Ron; Jaddoe, Vincent W. V.; Lok, Anja; van Rijn Bas, B.; Völzke, Henry; Cecil, Charlotte A. M.; Felix, Janine F. ... & Grabe, Hans J.
  
• The interplay between micro RNAs and genetic liability to Alzheimer‘s Disease on memory trajectories in the general population. Psychiatry Research, 323, 115141.
  Van der Auwera, Sandra; Garvert, Linda; Ameling, Sabine; Völzke, Henry; Nauck, Matthias; Völker, Uwe & Grabe, Hans J.