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7. Exploring the overlap between alopecia areata and major depressive disorder: Epidemiological and genetic perspectives.

Author

Foo, J. C., Redler, S., Forstner, A. J., Basmanav, F. B., Pethukova, L., Guo, J., Streit, F., Witt, S. H., Sirignano, L., Zillich, L., Awasthi, S., Ripke, S., Christiano, A. M., Tesch, F., Schmitt, J., Nöthen, M. M., Betz, R. C., Rietschel, M., and Frank, J.

Subjects
MENTAL depression, GENETIC disorders, DISEASE risk factors, MAJOR histocompatibility complex, MONOGENIC & polygenic inheritance (Genetics), ALOPECIA areata
Abstract

Background: Research suggests that Alopecia areata (AA) and Major Depressive Disorder (MDD) show substantial comorbidity. To date, no study has investigated the hypothesis that this is attributable to shared genetic aetiology. Objectives: To investigate AA‐MDD comorbidity on the epidemiological and molecular genetic levels. Methods: First, epidemiological analyses were performed using data from a cohort of adult German health insurance beneficiaries (n = 1.855 million) to determine the population‐based prevalence of AA‐MDD comorbidity. Second, analyses were performed to determine the prevalence of MDD in a clinical AA case–control sample with data on psychiatric phenotypes, stratifying for demographic factors to identify possible contributing factors to AA‐MDD comorbidity. Third, the genetic overlap between AA and MDD was investigated using a polygenic risk score (PRS) approach and linkage disequilibrium score (LDSC) regression. For PRS, summary statistics from a large MDD GWAS meta‐analysis (PGC‐MD2) were used as the training sample, while a Central European AA cohort, including the above‐mentioned AA patients, and an independent replication US‐AA cohort were used as target samples. LDSC was performed using summary statistics of PGC‐MD2 and the largest AA meta‐analysis to date. Results: High levels of AA‐MDD comorbidity were reported in the population‐based (MDD in 24% of AA patients), and clinical samples (MDD in 44% of AA patients). MDD‐PRS explained a modest proportion of variance in AA case–control status (R2 = 1%). This signal was limited to the major histocompatibility complex (MHC) region on chromosome 6. LDSC regression (excluding MHC) revealed no significant genetic correlation between AA and MDD. Conclusions: As in previous research, AA patients showed an increased prevalence of MDD. The present analyses suggest that genetic overlap may be confined to the MHC region, which is implicated in immune function. More detailed investigation is required to refine understanding of how the MHC is involved in the development of AA and MDD comorbidity. [ABSTRACT FROM AUTHOR]

Published
2023
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8. Hedgerow Gardens Provide Floral Resources for Diverse Insect Visitors to Avocado Flowers in Southern California.

Author

Frankie, G. W., Witt, S. L., Pawelek, J. C., Faber, B., Coville, R. E., Rizzardi, M. A., Chase, M. H., O'Sullivan, J., and Seltmann, K. C.

Subjects
*WINDBREAKS, shelterbelts, etc., *INSECTS, *HONEYBEES, *AVOCADO, *GARDENS, *FLOWERS, *CUT flowers
Abstract

This document provides a concise summary of the article titled "Hedgerow Gardens Provide Floral Resources for Diverse Insect Visitors to Avocado Flowers in Southern California." The article discusses the role of hedgerow gardens in supporting diverse insect populations in avocado orchards in Southern California. The study collected data on bee species from control and treatment sites on three ranches from 2014-2019 and provides a list of bee species collected during this period. Notably, the study discovered the first record of the genus and species Crawfordapis luctuosa in California and the USA. [Extracted from the article]

Published
2023
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11. Response to the letter by Esteves et al.

Author

Send, T. S., Gilles, M., Codd, V., Wolf, I. A. C., Bardtke, S., Streit, F., Strohmaier, J., Frank, J., Schendel, D., Sütterlin, M. W., Denniff, M., Laucht, M., Samani, N. J., Deuschle, M., Rietschel, M., and Witt, S. H.

Published
2018
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22. Identification of a non-classical three-dimensional nuclear localization signal in the intestinal fatty acid binding protein

Author

Suárez Martins, Mariana Carolina, Canclini, Lucía, Esteves, Adriana, Witt, S. N., Suárez Martins Mariana Carolina, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología., Canclini Lucía, IIBCE, and Esteves Adriana, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.

Subjects
Protein Conformation, alpha-Helical, 0301 basic medicine, Nuclear localization signals, Cell Lines, Nuclear Localization Signals, Lysine, Plasma protein binding, Biochemistry, 0302 clinical medicine, Protein structure, Medicine and Health Sciences, Amino Acids, Peptide sequence, Zebrafish, Recombinant proteins, Microscopy, Confocal, Multidisciplinary, Organic Compounds, Chemistry, Fatty Acids, Eukaryota, Animal Models, Lipids, Recombinant Proteins, Subcellular Localization, Experimental Organism Systems, Osteichthyes, Physical Sciences, Vertebrates, Medicine, Biological Cultures, Basic Amino Acids, Anatomy, Cellular Structures and Organelles, Research Article, Protein Binding, Science, Research and Analysis Methods, Arginine, Fatty Acid-Binding Proteins, 03 medical and health sciences, Model Organisms, Protein binding, Animals, Humans, NLS, Amino Acid Sequence, Cell Nucleus, Organic Chemistry, Chemical Compounds, Organisms, Wild type, Biology and Life Sciences, Proteins, Cell Biology, Zebrafish Proteins, Subcellular localization, Zebrafish proteins, Gastrointestinal Tract, Fish, 030104 developmental biology, Mutagenesis, Animal Studies, Caco-2 Cells, Zoology, Digestive System, 030217 neurology & neurosurgery, Nuclear localization sequence, Oleic Acid
Abstract

The intestinal fatty acid binding protein (FABP) is a small protein expressed along the small intestine that bind long-chain fatty acids and other hydrophobic ligands. Several lines of evidence suggest that, once in the nucleus, it interacts with nuclear receptors, activating them and thus transferring the bound ligand into the nucleus. Previous work by our group suggests that FABP2 would participate in the cytoplasm-nucleus translocation of fatty acids. Because the consensus NLS is absent in the sequence of FABP2, we propose that a 3D signal could be responsible for its nuclear translocation. The results obtained by transfection assays of recombinant wild type and mutated forms ofDanio rerioFabp2 in Caco-2 cell cultures, showed that lysine 17, arginine 29 and lysine 30 residues, which are located in the helix-turn-helix region, would constitute a functional non-classical three-dimensional NLS.

Published
2020

37. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder

Author

Schwarz, E., Doan, N. T., Pergola, G., Westlye, L. T., Kaufmann, T., Wolfers, T., Brecheisen, R., Quarto, T., Ing, A. J., Di Carlo, P., Gurholt, T. P., Harms, R. L., Noirhomme, Q., Moberget, T., Agartz, I., Andreassen, O. A., Bellani, M., Bertolino, A., Blasi, G., Brambilla, P., Buitelaar, J. K., Cervenka, S., Flyckt, L., Frangou, S., Franke, B., Hall, J., Heslenfeld, D. J., Kirsch, P., Mcintosh, A. M., Nothen, M. M., Papassotiropoulos, A., de Quervain, D. J. -F., Rietschel, M., Schumann, G., Tost, H., Witt, S. H., Zink, M., Meyer-Lindenberg, A., Bettella, F., Brandt, C. L., Clarke, T. -K., Coynel, D., Degenhardt, F., Djurovic, S., Eisenacher, S., Fastenrath, M., Fatouros-Bergman, H., Forstner, A. J., Frank, J., Gambi, F., Gelao, B., Geschwind, L., Di Giannantonio, M., Di Giorgio, A., Hartman, C. A., Heilmann-Heimbach, S., Herms, S., Hoekstra, P. J., Hoffmann, P., Hoogman, M., Jonsson, E. G., Loos, E., Maggioni, E., Oosterlaan, J., Papalino, M., Rampino, A., Romaniuk, L., Selvaggi, P., Sepede, G., Sonderby, I. E., Spalek, K., Sussmann, J. E., Thompson, P. M., Vasquez, A. A., Vogler, C., Whalley, H., Farde, L., Engberg, G., Erhardt, S., Schwieler, L., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Cognitive Psychology, IBBA, Behavioural Sciences, Elvira Brattico / Principal Investigator, Department of Psychology and Logopedics, Cognitive Brain Research Unit, Faculty of Medicine, University of Helsinki, General Paediatrics, ARD - Amsterdam Reproduction and Development, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Multiscale Imaging of Brain Connectivity, RS: FPN CN 11, Vision, and RS: FPN CN 1

Subjects
0301 basic medicine, Male, Multivariate statistics, Bipolar Disorder, SEGMENTATION, 3124 Neurology and psychiatry, Machine Learning, 0302 clinical medicine, DEFICITS, Gray Matter, Psychiatry, RISK, medicine.diagnostic_test, 220 Statistical Imaging Neuroscience, LIKELIHOOD ESTIMATION, Middle Aged, MRI SCANS, Magnetic Resonance Imaging, Justice and Strong Institutions, 3. Good health, Psychiatry and Mental health, medicine.anatomical_structure, bipolar disorders, Schizophrenia, Female, brain structural patterns, MRI, Adult, SDG 16 - Peace, Adolescent, Brain Structure and Function, Grey matter, Psykiatri, CLASSIFICATION, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Text mining, medicine, Humans, Bipolar disorder, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, METAANALYSIS, schizophrenia, grey matter alterations, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, 1ST-EPISODE, SDG 16 - Peace, Justice and Strong Institutions, Magnetic resonance imaging, medicine.disease, 030104 developmental biology, Sample size determination, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, VOLUME, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 202693.pdf (Publisher’s version ) (Open Access) Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.

Published
2019

38. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder

Author

Demontis, D, Walters, R, Martin, J, Mattheisen, M, Als, T, Agerbo, E, Baldursson, G, Belliveau, R, Bybjerg-Grauholm, J, Baekvad-Hansen, M, Cerrato, F, Chambert, K, Churchhouse, C, Dumont, A, Eriksson, N, Gandal, M, Goldstein, J, Grasby, K, Grove, J, Gudmundsson, O, Hansen, C, Hauberg, M, Hollegaard, M, Howrigan, D, Huang, H, Maller, J, Martin, A, Martin, N, Moran, J, Pallesen, J, Palmer, D, Pedersen, C, Pedersen, M, Poterba, T, Poulsen, J, Ripke, S, Robinson, E, Satterstrom, F, Stefansson, H, Stevens, C, Turley, P, Walters, G, Won, H, Wright, M, Andreassen, O, Asherson, P, Burton, C, Boomsma, D, Cormand, B, Dalsgaard, S, Franke, B, Gelernter, J, Geschwind, D, Hakonarson, H, Haavik, J, Kranzler, H, Kuntsi, J, Langley, K, Lesch, K, Middeldorp, C, Reif, A, Rohde, L, Roussos, P, Schachar, R, Sklar, P, Sonuga-Barke, E, Sullivan, P, Thapar, A, Tung, J, Waldman, I, Medland, S, Stefansson, K, Nordentoft, M, Hougaard, D, Werge, T, Mors, O, Mortensen, P, Daly, M, Faraone, S, Borglum, A, Neale, B, Albayrak, O, Anney, R, Arranz, M, Banaschewski, T, Bau, C, Biederman, J, Buitelaar, J, Casas, M, Charach, A, Crosbie, J, Dempfle, A, Doyle, A, Ebstein, R, Elia, J, Freitag, C, Focker, M, Gill, M, Grevet, E, Hawi, Z, Hebebrand, J, Herpertz-Dahlmann, B, Hervas, A, Hinney, A, Hohmann, S, Holmans, P, Hutz, M, Ickowitz, A, Johansson, S, Kent, L, Kittel-Schneider, S, Lambregts-Rommelse, N, Lehmkuhl, G, Loo, S, McGough, J, Meyer, J, Mick, E, Middletion, F, Miranda, A, Mota, N, Mulas, F, Mulligan, A, Nelson, F, Nguyen, T, Oades, R, O'Donovan, M, Owen, M, Palmason, H, Ramos-Quiroga, J, Renner, T, Ribases, M, Rietschel, M, Rivero, O, Romanos, J, Romanos, M, Rothenberger, A, Royers, H, Sanchez-Mora, C, Scherag, A, Schimmelmann, B, Schafer, H, Sergeant, J, Sinzig, J, Smalley, S, Steinhausen, H, Thompson, M, Todorov, A, Vasquez, A, Walitza, S, Wang, Y, Warnke, A, Williams, N, Witt, S, Yang, L, Zayats, T, Zhang-James, Y, Smith, G, Davies, G, Ehli, E, Evans, D, Fedko, I, Greven, C, Groen-Blokhuis, M, Guxens, M, Hammerschlag, A, Hartman, C, Heinrich, J, Hottenga, J, Hudziak, J, Jugessur, A, Kemp, J, Krapohl, E, Murcia, M, Myhre, R, Nolte, I, Nyholt, D, Ormel, J, Ouwens, K, Pappa, I, Pennell, C, Plomin, R, Ring, S, Standl, M, Stergiakouli, E, St Pourcain, B, Stoltenberg, C, Sunyer, J, Thiering, E, Tiemeier, H, Tiesler, C, Timpson, N, Trzaskowski, M, van der Most, P, Vilor-Tejedor, N, Wang, C, Whitehouse, A, Zhao, H, Agee, M, Alipanahi, B, Auton, A, Bell, R, Bryc, K, Elson, S, Fontanillas, P, Furlotte, N, Hinds, D, Hromatka, B, Huber, K, Kleinman, A, Litterman, N, McIntyre, M, Mountain, J, Northover, C, Pitts, S, Sathirapongsasuti, J, Sazonova, O, Shelton, J, Shringarpure, S, Tian, C, Vacic, V, Wilson, C, ADHD Working Grp Psychiat Genomics, Early Lifecourse Genetic, 23andMe Res Team, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Psychiatry, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), 23andme Research Team, University of St Andrews. Cellular Medicine Division, University of St Andrews. Institute of Behavioural and Neural Sciences, University of St Andrews. School of Medicine, Child and Adolescent Psychiatry / Psychology, Erasmus MC other, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Clinical Neuropsychology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Personalized Medicine, Clinical Child and Family Studies, LEARN! - Child rearing, and APH - Methodology

Subjects
Netherlands Twin Register (NTR), Male, Trastorns per dèficit d'atenció amb hiperactivitat en els infants, LD SCORE REGRESSION, Medizin, Genome-wide association study, US CHILDREN, Genoma humà, Attention deficit disorder with hyperactivity in children, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, 2.1 Biological and endogenous factors, POLYGENIC RISK, Aetiology, Child, IDENTIFIES 11, SEXUAL-BEHAVIOR, Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, Pediatric, 0303 health sciences, education.field_of_study, Genome, Genetic Predisposition to Disease/genetics, 1184 Genetics, developmental biology, physiology, Brain, 3rd-DAS, Single Nucleotide, Biological Sciences, Polymorphism, Single Nucleotide/genetics, 3. Good health, Mental Health, Meta-analysis, Child, Preschool, Genetic Loci/genetics, Genome-Wide Association Study/methods, Trastorns per dèficit d'atenció amb hiperactivitat en els adults, Attention Deficit Disorder (ADD), Female, Attention Deficit Disorder with Hyperactivity/genetics, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, SDG 4 - Quality Education, Clinical psychology, Risk, Adolescent, DEFICIT HYPERACTIVITY DISORDER, Concordance, Population, PROVIDES INSIGHTS, QH426 Genetics, Biology, Quantitative trait locus, Brain/physiology, Polymorphism, Single Nucleotide, 23andMe Research Team, behavioral disciplines and activities, Gene Expression Regulation/genetics, Article, 150 000 MR Techniques in Brain Function, GENETIC ARCHITECTURE, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Clinical Research, Behavioral and Social Science, mental disorders, medicine, Genetics, Attention deficit hyperactivity disorder, Humans, Genetic Predisposition to Disease, Polymorphism, education, Preschool, QH426, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], ASSOCIATION METAANALYSIS, Prevention, Human Genome, Case-control study, MAJOR DEPRESSION, medicine.disease, Attention Deficit Hyperactivity Disorder (ADHD), Genetic architecture, Brain Disorders, ADHD Working Group of the Psychiatric Genomics Consortium, Gene Expression Regulation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, RC0321, Attention deficit disorder with hyperactivity in adults, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology
Abstract

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits. Postprint

Published
2019

39. Microscopic origin of the charge transfer in single crystals based on thiophene derivatives: A combined NEXAFS and density functional theory approach.

Author

Chernenkaya, A., Morherr, A., Backes, S., Popp, W., Witt, S., Kozina, X., Nepijko, S. A., Bolte, M., Medjanik, K., Öhrwall, G., Krellner, C., Baumgarten, M., Elmers, H. J., Schönhense, G., Jeschke, H. O., and Valentí, R.

Subjects
CRYSTALLOGRAPHY, SINGLE crystals, CRYSTAL whiskers, THIOPHENE derivatives, DENSITY functional theory
Abstract

We have investigated the charge transfer mechanism in single crystals of DTBDT-TCNQ and DTBDT-F4TCNQ (where DTBDT is dithieno[2,3-d;2',3'-d'] benzo[1,2-b;4,5-b']dithiophene) using a combination of near-edge X-ray absorption spectroscopy (NEXAFS) and density functional theory calculations (DFT) including final state effects beyond the sudden state approximation. In particular, we find that a description that considers the partial screening of the electron-hole Coulomb correlation on a static level as well as the rearrangement of electronic density shows excellent agreement with experiment and allows to uncover the details of the charge transfer mechanism in DTBDT-TCNQ and DTBDT-F4 TCNQ, as well as a reinterpretation of previous NEXAFS data on pure TCNQ. Finally, we further show that almost the same quality of agreement between theoretical results and experiment is obtained by the much faster Z+1/2 approximation, where the core hole effects are simulated by replacing N or F with atomic number Z with the neighboring atom with atomic number Z+1/2. [ABSTRACT FROM AUTHOR]

Published
2016
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43. Response to Therapeutic Sleep Deprivation: A Naturalistic Study of Clinical and Genetic Factors and Post-treatment Depressive Symptom Trajectory

Author

Trautmann, N., Foo, J., Frank, J., Witt, S., Streit, F., Treutlein, J., Conrad von Heydendorff, S., Gilles, M., Forstner, A.J., Ebner-Priemer, U., Nöthen, M.M., Deuschle, M., Rietschel, M., Major Depressive Disorder Working Group of the, Psychiatric Genomics Consortium, and Jones, Lisa

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Visual analogue scale, BF, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Naturalistic observation, Internal medicine, Epidemiology, medicine, Humans, Longitudinal Studies, ddc:796, Depression (differential diagnoses), Psychiatric Status Rating Scales, Pharmacology, Depressive Disorder, Major, business.industry, Middle Aged, medicine.disease, Psychiatry and Mental health, Sleep deprivation, Athletic & outdoor sports & games, Treatment Outcome, 030104 developmental biology, Mood, Clinical Global Impression, RC0321, Sleep Deprivation, Major depressive disorder, Antidepressant, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Cohort study
Abstract

Research has shown that therapeutic sleep deprivation (SD) has rapid antidepressant effects in the majority of depressed patients. Investigation of factors preceding and accompanying these effects may facilitate the identification of the underlying biological mechanisms. This exploratory study aimed to examine clinical and genetic factors predicting response to SD and determine the impact of SD on illness course. Mood and tiredness during SD were also assessed via visual analogue scales (VAS). Depressed inpatients (n = 78) and healthy controls (n = 15) underwent ~36hrs of SD. Response to SD was defined as a score of ≤2 on the Clinical Global Impression Scale for Global Improvement. Depressive symptom trajectories were evaluated for up to a month using self/expert ratings. Impact of genetic burden was calculated using polygenic risk scores for major depressive disorder. 72% of patients responded to SD. Responders and nonresponders did not differ in baseline self/expert depression symptom ratings, but mood subjectively measured by VAS scale differed. Response was associated with lower age (p= 0.007) and later age at life-time disease onset (p= 0.003). Higher genetic burden of depression was observed in non-responders than healthy controls. Up to a month post-SD, depressive symptoms decreased in both patients groups, but more in responders, in whom effects were sustained. The present findings suggest that re-examining SD with a greater focus on biological mechanisms will lead to better understanding of mechanisms of depression.

Published
2018

44. Improving genetic prediction by leveraging genetic correlations among human diseases and traits

Author

Maier, R. M., Zhu, Z., Lee, S. H., Trzaskowski, M., Ruderfer, D. M., Stahl, E. A., Ripke, S., Wray, N. R., Yang, J., Visscher, P. M., Robinson, M. R., Forstner, A. J., Mcquillin, A., Trubetskoy, V., Wang, W., Wang, Y., Coleman, J. R. I., Gaspar, H. A., Leeuw, C. A., Whitehead Pavlides, J. M., Olde Loohuis, L. M., Pers, T. H., Lee, P. H., Charney, A. W., Dobbyn, A. L., Huckins, L., Boocock, J., Giambartolomei, C., Roussos, P., Mullins, N., Awasthi, S., Agerbo, E., Als, T. D., Pedersen, C. B., Grove, J., Kupka, R., Regeer, E. J., Anjorin, A., Casas, M., Mahon, P. B., Allardyce, J., Escott-Price, V., Forty, L., Fraser, C., Kogevinas, M., Frank, J., Streit, F., Strohmaier, J., Treutlein, J., Witt, S. H., Kennedy, J. L., Strauss, J. S., Garnham, J., O Donovan, C., Slaney, C., Steinberg, S., Thorgeirsson, T. E., Hautzinger, M., Steffens, M., Perlis, R. H., Sánchez-Mora, C., Hipolito, M., Lawson, W. B., Nwulia, E. A., Levy, S. E., Foroud, T. M., Jamain, S., Young, A. H., Mckay, J. D., Albani, D., Zandi, P., Potash, J. B., Zhang, P., Raymond Depaulo, J., Bergen, S. E., Juréus, A., Karlsson, R., Kandaswamy, R., Mcguffin, P., Rivera, M., Lissowska, J., Cruceanu, C., Lucae, S., Cervantes, P., Budde, M., Gade, K., Heilbronner, U., Pedersen, M. G., Morris, D. W., Weickert, C. S., Weickert, T. W., Macintyre, D. J., Lawrence, J., Elvsåshagen, T., Smeland, O. B., Djurovic, S., Xi, S., Green, E. K., Czerski, P. M., Hauser, J., Xu, W., Vedder, H., Oruc, L., Spijker, A. T., Gordon, S. D., Medland, S. E., Curtis, D., Mühleisen, T. W., Badner, J. A., Scheftner, W. A., Sigurdsson, E., Schork, N. J., Schatzberg, A. F., Bækvad-Hansen, M., Bybjerg-Grauholm, J., Hansen, C. S., Knowles, J. A., Szelinger, S., Montgomery, G. W., Boks, M., Adolfsson, A. N., Hoffmann, P., Bauer, M., Pfennig, A., Leber, M., Kittel-Schneider, S., Reif, A., Del-Favero, J., Fischer, S. B., Herms, S., Reinbold, C. S., Degenhardt, F., Koller, A. C., Maaser, A., Ori, A. P. S., Dale, A. M., Fan, C. C., Greenwood, T. A., Nievergelt, C. M., Shehktman, T., Shilling, P. D., Byerley, W., Bunney, W., Alliey-Rodriguez, N., Clarke, T. K., Liu, C., Coryell, W., Akil, H., Burmeister, M., Flickinger, M., Li, J. Z., Mcinnis, M. G., Meng, F., Thompson, R. C., Watson, S. J., Zollner, S., Guan, W., Green, M. J., Craig, D., Sobell, J. L., Milani, L., Gordon-Smith, Katherine, Knott, Sarah, Perry, Amy, Parra, J. G., Mayoral, F., Rivas, F., Rice, J. P., Barchas, J. D., Børglum, A. D., Mortensen, P. B., Mors, O., Grigoroiu-Serbanescu, M., Bellivier, F., Etain, B., Leboyer, M., Ramos-Quiroga, J. A., Agartz, I., Amin, F., Azevedo, M. H., Bass, N., Black, D. W., Blackwood, D. H. R., Bruggeman, R., Buccola, N. G., Choudhury, K., Cloninger, C. R., Corvin, A., Craddock, N., Daly, M. J., Datta, S., Donohoe, G. J., Duan, J., Dudbridge, F., Fanous, A., Freedman, R., Freimer, N. B., Friedl, M., Gill, M., Gurling, H., Haan, L., Hamshere, M. L., Hartmann, A. M., Holmans, P. A., Kahn, R. S., Keller, M. C., Kenny, E., Kirov, G. K., Krabbendam, L., Krasucki, R., Lencz, T., Levinson, D. F., Lieberman, J. A., Lin, D. -Y, Linszen, D. H., Magnusson, P. K. E., Maier, W., Malhotra, A. K., Mattheisen, M., Mattingsdal, M., Mccarroll, S. A., Medeiros, H., Melle, I., Milanova, V., Myin-Germeys, I., Neale, B. M., Ophoff, R. A., Owen, M. J., Pimm, J., Purcell, S. M., Puri, V., Digby Quested, Rossin, L., Sanders, A. R., Shi, J., Sklar, P., St Clair, D., Stroup, T. S., Os, J., Wiersma, D., Zammit, S., Maier, Robert M, Zhu, Zhihong, Lee, Sang Hong, Trzaskowski, Maciej, Ruderfer, Douglas M, Stahl, Eli A, Ripke, Stephan, Wray, Naomi R, Yang, Jian, Visscher, Peter M, Robinson, Matthew R, Bipolar Disorder Working Grp Psy, Schizophrenia Working Grp Psychiat, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, and Psychiatry

Subjects
0301 basic medicine, Bipolar Disorder, Chemistry(all), Science, General Physics and Astronomy, Genomics, Genome-wide association study, Computational biology, Biology, Physics and Astronomy(all), Risk Assessment, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Article, predictive medicine, quantitative trait, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Pleiotropy, Genetic Pleiotropy, Humans, Genetic Predisposition to Disease, lcsh:Science, Multidisciplinary, Models, Statistical, Bipolar Disorder/genetics, Genome-Wide Association Study, Schizophrenia/genetics, Biochemistry, Genetics and Molecular Biology(all), General Chemistry, Precision medicine, R1, Biobank, 3. Good health, genome wide association studies, 030104 developmental biology, Trait, Schizophrenia, statistical methods, lcsh:Q, Risk assessment, 030217 neurology & neurosurgery, Genetics and Molecular Biology(all)
Abstract

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7% for height to 47% for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait., Genetic prediction of complex traits so far has limited accuracy because of insufficient understanding of the genetic risk. Here, Maier et al. develop an improved method for trait prediction that makes use of genetic correlations between traits and apply it to summary statistics of psychiatric diseases.

Published
2018

49. Baricitinib inhibits radiographic progression of structural joint damage at 1 year in patients with rheumatoid arthritis (RA) and an inadequate response to csDMARDs

Author

van der Heijde, D, Dougados, M, Chen, YC, Greenwald, M, Drescher, E, Klar, R, Xie, L, de la Torre, I, Rooney, T, Witt, S, Schlichting, D, de Bono, S, Emery, P, and Röhl, K

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Baricitinib (bari), a JAK1/2 inhibitor, was efficacious in a 24-week (wk) Ph 3 study in patients (pts) with active RA and an inadequate response (IR) to conventional synthetic DMARDs (csDMARDs) (RA-BUILD). The objective of this analysis was to evaluate radiographic progression of structural[for full text, please go to the a.m. URL], 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Published
2017
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50. Study protocol of the ASD-Net, the German research consortium for the study of Autism Spectrum Disorder across the lifespan: From a better etiological understanding, through valid diagnosis, to more effective health care

Author

Kamp-Becker, I., Poustka, L., Bachmann, C., Ehrlich, S., Hoffmann, F., Kanske, P., Kirsch, P., Krach, S., Paulus, F., Rietschel, M., Roepke, S., Roesner, V., Schad-Hansjosten, T., Singer, T., Stroth, S., Witt, S., and Wermter, A.

Subjects
Male, Biomedical Research, lcsh:RC435-571, Autism Spectrum Disorder, ASD-net, Research, Oxytocin, behavioral disciplines and activities, Study Protocol, Genetic, Social competence training, lcsh:Psychiatry, Germany, Diagnosis, mental disorders, Screening, Humans, Disabled Persons, Female, Therapy, Cooperative Behavior, Health economics, German research network for mental disorders, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Abstract

Background Autism Spectrum Disorder (ASD) is a severe, lifelong neurodevelopmental disorder with early onset that places a heavy burden on affected individuals and their families. Due to the need for highly specialized health, educational and vocational services, ASD is a cost-intensive disorder, and strain on health care systems increases with increasing age of the affected individual. Methods The ASD-Net will study Germany’s largest cohort of patients with ASD over the lifespan. By combining methodological expertise from all levels of clinical research, the ASD-Net will follow a translational approach necessary to identify neurobiological pathways of different phenotypes and their appropriate identification and treatment. The work of the ASD-Net will be organized into three clusters concentrating on diagnostics, therapy and health economics. In the diagnostic cluster, data from a large, well-characterized sample (N = 2568) will be analyzed to improve the efficiency of diagnostic procedures. Pattern classification methods (machine learning) will be used to identify algorithms for screening purposes. In a second step, the developed algorithm will be tested in an independent sample. In the therapy cluster, we will unravel how an ASD-specific social skills training with concomitant oxytocin administration can modulate behavior through neurobiological pathways. For the first time, we will characterize long-term effects of a social skills training combined with oxytocin treatment on behavioral and neurobiological phenotypes. Also acute effects of oxytocin will be investigated to delineate general and specific effects of additional oxytocin treatment in order to develop biologically plausible models for symptoms and successful therapeutic interventions in ASD. Finally, in the health economics cluster, we will assess service utilization and ASD-related costs in order to identify potential needs and cost savings specifically tailored to Germany. The ASD-Net has been established as part of the German Research Network for Mental Disorders, funded by the BMBF (German Federal Ministry of Education and Research). Discussion The highly integrated structure of the ASD-Net guarantees sustained collaboration of clinicians and researchers to alleviate individual distress, harm, and social disability of patients with ASD and reduce costs to the German health care system. Trial registration Both clinical trials of the ASD-Net are registered in the German Clinical Trials Register: DRKS00008952 (registered on August 4, 2015) and DRKS00010053 (registered on April 8, 2016). peerReviewed

Published
2017

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