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Polygenic scores for psychiatric disease: from research tool to clinical application

Till F. M. Andlauer, Markus M. Nöthen
2020 Medizinische Genetik  
Conflict of interest: Till Andlauer and Markus Nöthen state that there are no conflicts of interest.  ... 
doi:10.1515/medgen-2020-2006 fatcat:n7nolgteindtfhg2bnrefyo27y

Genetic variation in WNT9B increases relapse hazard in multiple sclerosis

Marijne Vandebergh, Till F M Andlauer, Yuan Zhou, Klara Mallants, Friederike Held, Lilian Aly, Bruce V Taylor, Bernhard Hemmer, Bénédicte Dubois, An Goris
2021 Annals of Neurology  
M ultiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS).  ... 
doi:10.1002/ana.26061 pmid:33704824 fatcat:dhazfdwmcvhhxi55j6hhtaey24

Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes

Hans Faber, Dunja Kurtoic, Gurumoorthy Krishnamoorthy, Peter Weber, Benno Pütz, Bertram Müller-Myhsok, Frank Weber, Till F M Andlauer
2020 Frontiers in Immunology  
TA and BM-M were supported by the BMBF through the Integrated Network IntegraMent, under the auspices of the e:Med Programme (grant 01ZX1614J).  ...  BM-M and FW supervised the study. HF and TA drafted the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.  ...  Copyright © 2020 Faber, Kurtoic, Krishnamoorthy, Weber, Pütz, Müller-Myhsok, Weber and Andlauer.  ... 
doi:10.3389/fimmu.2020.02165 pmid:33072080 pmcid:PMC7531036 fatcat:s7kughrf4bhxhbwwx7d3qjajfy

A multi‐informant and multi‐polygenic approach to understanding predictors of peer victimisation in childhood and adolescence

Jessica M. Armitage, Geneviève Morneau‐Vaillancourt, Jean‐Baptiste Pingault, Till F. M. Andlauer, Stéphane Paquin, Stéphanie Langevin, Mara Brendgen, Ginette Dionne, Jean Séguin, Guy Rouleau, Frank Vitaro, Isabelle Ouellet‐Morin (+1 others)
2022 JCPP Advances  
Victimisation scores based on age and informant N %Male M(SD) Min Max Age 7 Self-reported 527 51.0 0.71(0.52) 0.00 2.00 Teacher-reported 476 51.3 0.26(0.37) 0.00 2.00 Peer-reported 465 50.8 −0.05(0.96)  ...  Peer-reported victimisation When investigating predictions using our peer-reported composite, associations were found using the PGS for educational attainment F I G U R E 1 Regression coefficients from  ... 
doi:10.1002/jcv2.12063 fatcat:kr655x72mnaszjcjunv3reijgu

Treatment response classes in major depressive disorder identified by model-based clustering and validated by clinical prediction models

Riya Paul, Till. F. M. Andlauer, Darina Czamara, David Hoehn, Susanne Lucae, Benno Pütz, Cathryn M. Lewis, Rudolf Uher, Bertram Müller-Myhsok, Marcus Ising, Philipp G. Sämann
2019 Translational Psychiatry  
One explanation is the use of a binary cutoff (25 kg/m 2 ) in the positive report 66 , which may point to a non-linear relationship.  ...  Arrows indicate lower (↓), higher (↑), or within (0) positioning regarding the 95% CI of the respective parameter distribution. ≥0.25 and <0.40, medium effect; ≥0.40: large effect. b c Cohen's f:  ... 
doi:10.1038/s41398-019-0524-4 pmid:31383853 pmcid:PMC6683145 fatcat:4b4hku2prnhm3jnndgzh4uppv4

Drep-2 is a novel synaptic protein important for learning and memory

Till F M Andlauer, Sabrina Scholz-Kornehl, Rui Tian, Marieluise Kirchner, Husam A Babikir, Harald Depner, Bernhard Loll, Christine Quentin, Varun K Gupta, Matthew G Holt, Shubham Dipt, Michael Cressy (+5 others)
2014 eLife  
Scale bars: 2 µm.  ...  However, Andlauer et al. observed that flies lacking both Drep-2 and FMRP can learn normally.  ... 
doi:10.7554/elife.03895 pmid:25392983 pmcid:PMC4229683 fatcat:bqsidvjssjh4no6d3r3djhmdka

S13. IMPACT OF POLYGENIC AND POLY-ENVIRONMENTAL RISK FACTORS ON A PSYCHOSIS RISK PHENOTYPE EXPLAINED THROUGH BRAIN STRUCTURE

Tina Meller, Simon Schmitt, Frederike Stein, Katharina Brosch, Dominik Grotegerd, Katharina Dohm, Susanne Meinert, Till F M Andlauer, Marcella Rietschel, Bertram Müller-Myhsok, Markus M Nöthen, Udo Dannlowski (+3 others)
2020 Schizophrenia Bulletin  
M. Andlauer 3 , Marcella Rietschel 4 , Bertram Müller-Myhsok 3 , Markus M.  ...  F.  ... 
doi:10.1093/schbul/sbaa031.079 fatcat:eid67xfywfa2dj6sjf4jij4m7q

"The Heidelberg Five" Personality Dimensions: Genome-wide Associations, Polygenic Risk for Neuroticism, and Psychopathology 20 Years after Assessment [article]

Urs Heilbronner, Sergi Papiol, Monika Budde, Till F. M. Andlauer, Jana Strohmaier, Fabian Streit, Josef Frank, Franziska Degenhardt, Stefanie Heilmann-Heimbach, Stephanie Witt, Andreas J. Forstner, Adrian Loerbroks (+6 others)
2020 bioRxiv   pre-print
The HeiDE study ("Heidelberger Langzeitstudie zu Risikofaktoren und Diagnose chronischer Erkrankungen") is a longitudinal population-based study that started in the 1990s and, at baseline, assessed an array of health-related personality questionnaires in 5 133 individuals. Five latent personality dimensions (The Heidelberg Five) were identified and interpreted as Emotional Lability (ELAB), Lack of Behavioral Control (LBCN), Type A Behavior (TYAB), Locus of Control over Disease (LOCC), and
more » ... ticism (PSYC). A subset of participants (n=3 268; after quality control) were genotyped on whole-genome arrays at follow-up. To further characterize The Heidelberg Five, we analyzed genomic underpinnings, their relations to the genetic basis of the Big Five trait Neuroticism, and longitudinal associations with lifetime psychiatric symptoms. SNP-based heritability was significant for ELAB (34%) and LBCN (29%). Five separate genome-wide association studies (GWAS) using factor scores on personality dimensions as phenotypes were conducted, only the phenotype PSYC yielded a genome-wide significant finding (p<5×10-8, top SNP rs138223660). Gene-based analyses identified significant findings for ELAB (Integrin Subunit Beta 5), TYAB (Coiled-coil Domain Containing 83), and PSYC (Nuclear Receptor Subfamily 1 Group H Member 4). Polygenic risk scores for Neuroticism, phenotypically related to ELAB, were associated with ELAB, but not with the remaining Heidelberg Five. Longitudinally, all personality dimensions were related to depressive symptoms at follow-up, with ELAB, LBCN, and PSYC also associated with lifetime anxiety symptoms. These results highlight the clinical importance of health-related personality traits, and identify LBCN as a heritable "executive function" personality trait.
doi:10.1101/2020.03.23.003889 fatcat:ggqnkonau5fvxdimpkkgq46kby

Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release

Varun K. Gupta, Ulrike Pech, Anuradha Bhukel, Andreas Fulterer, Anatoli Ender, Stephan F. Mauermann, Till F. M. Andlauer, Emmanuel Antwi-Adjei, Christine Beuschel, Kerstin Thriene, Marta Maglione, Christine Quentin (+8 others)
2016 PLoS Biology  
We would like to thank M. Böhme for his technical help in STED imaging. We further thank M. G. Holt and S. T. Sweeney for reading the manuscript critically.  ...  The numbers indicate changes in fluorescence (ΔF/F in %). Scale bar: 10 μm.  ...  Scale bar: 50 μm.  ... 
doi:10.1371/journal.pbio.1002563 pmid:27684064 pmcid:PMC5042543 fatcat:pgpdsx5y4na73ijw3hwuenb5ay

Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta [article]

Till F. M. Andlauer, Jenny Link, Dorothea Martin, Malin Ryner, Christina Hermanrud, Verena Grummel, Michael Auer, Harald Hegen, Lilian Aly, Christiane Gasperi, Benjamin Knier, Bertram Müller-Myhsok (+10 others)
2020 medRxiv   pre-print
Manhattan plots of the (A-C, G-I) discovery-stage and (D-F, J-L) pooled discovery + replication GWAS, showing only the MHC region.  ...  (A-F) shows analyses for IFNβ-1a s.c., (G-L) for IFNβ-1b s.c. Manhattan plots of the MHC region of the GWAS on patients treated with IFNβ-1a s.c. or IFNβ-1b s.c.  ... 
doi:10.1101/2020.05.01.20086033 fatcat:vu7wrjo4snhppkqw2cfiesme44

Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning [article]

Helena Pelin, Marcus Ising, Frederike Stein, Susanne Meinert, Tina Meller, Katharina Brosch, Nils R. Winter, Axel Krug, Ramona Leenings, Hannah Lemke, Igor Nenadic, Stefanie Heilmann-Heimbach (+18 others)
2021 medRxiv   pre-print
Till Andlauer was supported by the BMBF through the DIFUTURE consortium of the Medical Informatics Initiative Germany (grant 01ZZ1804A) and the European Union's Horizon 2020 Research and Innovation Programme  ...  F: MDD PGS, significantly different in two one-vs-all analyses (lower in Cluster 0, p=0.008; higher in Cluster 4, corrected p=0.04).  ... 
doi:10.1101/2021.02.04.21251083 fatcat:s5c4oslyefb6bniptu36ipgzbq

Genetic factors influencing a neurobiological substrate for psychiatric disorders [article]

Till F. M. Andlauer, Thomas W. Mühleisen, Felix Hoffstaedter, Alexander Teumer, Katharina Wittfeld, Anja Teuber, Céline S. Reinbold, Robin Bülow, Svenja Caspers, Stefan Herms, Per Hoffmann, Heike Minnerup (+14 others)
2019 bioRxiv   pre-print
Evidence from meta-analyses of MRI-based brain morphometry suggested a common neurobiological substrate (CS) for psychiatric disorders in the dorsal anterior cingulate (dACC) and the anterior insular cortices (AIC). Methods: We analyzed the first principal component of voxel-based morphometric volumes forming the CS (hereafter abbreviated as CCS). We conducted genome-wide association studies (GWAS) of the CCS in four cohorts (discovery, n=2,271), followed by meta-analysis, and replication in a
more » ... ifth cohort (n=865). Secondary genetic and clinical imaging analyses were performed in two major depressive disorder case/control cohorts (n=967 cases and n=508 controls). Results: The single-nucleotide polymorphism (SNP) rs17076061 on chromosome 5q35.2 was associated with the CCS at genome-wide significance and replicated. Psychiatric cross-disorder polygenic risk scores were associated with the CCS at nominal significance. However, no significant genome-wide overlap between genetic variants influencing the CCS and genetic risk for different disorders was found after correction for multiple testing. Further secondary analyses revealed a dependence of the association of the identified variant on interactions with age. Conclusions: We identified a significant association between a genetic variant and a transdiagnostic psychiatric marker. The SNP maps to a locus harboring genes involved in neuronal development and regeneration. Dependence of this association on age and the absence of direct associations with major psychiatric disorders suggest an indirect relationship between the CCS and disease risk, contingent on environmental and additional, unknown genetic factors. Overall, our study indicates a complex interplay between common genetic variation and the function of brain regions affected in psychiatric patients.
doi:10.1101/774463 fatcat:5xgil5b2ibg7tpxpmtkbcpqu4u

Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning

Helena Pelin, Marcus Ising, Frederike Stein, Susanne Meinert, Tina Meller, Katharina Brosch, Nils R. Winter, Axel Krug, Ramona Leenings, Hannah Lemke, Igor Nenadić, Stefanie Heilmann-Heimbach (+18 others)
2021 Neuropsychopharmacology  
Till Andlauer was supported by the BMBF through the DIFUTURE consortium of the Medical Informatics Initiative Germany (grant 01ZZ1804A) and the European Union's Horizon 2020 Research and Innovation Programme  ...  M.; RI 908/11-1, RI 908/11-2 to M.R.; NO 246/10-1, NO 246/10-2 to M.M.N.; WI 3439/3-1, WI 3439/3-2 to S.W.  ... 
doi:10.1038/s41386-021-01051-0 pmid:34127797 fatcat:rdhsocgtsngpjbmtbrmygutpqa

GWAS META-analysis followed by MENDELIAN randomisation revealed potential control mechanisms for circulating α-klotho levels

Ingrid Gergei, Jie Zheng, Till F M Andlauer, Vincent Brandenburg, Nazanin Mirza-Schreiber, Bertram Müller-Myhsok, Bernhard K Krämer, Daniel Richard, Louise Falk, Sofia Movérare-Skrtic, Claes Ohlsson, George Davey Smith (+3 others)
2021 Human Molecular Genetics  
An F-test revealed the instrument to have an acceptable instrumental strength for subsequent MR analyses (F-statistic = 74.8).  ...  (B-F) Locus-specific Manhattan plots of the genome-wide significant loci at (B) the ABO locus, (C) the B4GALNT3 locus, (D) the CHST9 locus, (E) the KL locus and (F) the FGFR1 locus.  ... 
doi:10.1093/hmg/ddab263 pmid:34542150 pmcid:PMC8895756 fatcat:hcfbia4c4fdnlotdd3sjdr6rte

Genetic, Individual, and Familial Risk Correlates of Brain Network Controllability in Major Depressive Disorder [article]

Tim Hahn, Nils R. Winter, Jan Ernsting, Marius Gruber, Marco J. Mauritz, Lukas Fisch, Ramona Leenings, Kelvin Sarink, Julian Blanke, Vincent Holstein, Daniel Emden, Marie Beisemann (+18 others)
2021 arXiv   pre-print
This was not the case for modal controllability (F(1,685)=2.40, p=.122). (F( 1 , 1 623)=3.86, p=.050) as well as negatively associated with modal controllability (F(1,624)=4.88, p=.028).  ...  associated with whole-brain average controllability for healthy controls (F(1,814)=.04, p=.839) or MDD patients (F(1,687)=.08, p=.773).  ... 
arXiv:2107.10169v1 fatcat:lykm4ckia5bwzfu4h36ei2fkp4
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