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1. deepmriprep: Voxel-based Morphometry (VBM) Preprocessing via Deep Neural Networks

Author

Fisch, Lukas, Winter, Nils R., Goltermann, Janik, Barkhau, Carlotta, Emden, Daniel, Ernsting, Jan, Konowski, Maximilian, Leenings, Ramona, Borgers, Tiana, Flinkenflügel, Kira, Grotegerd, Dominik, Kraus, Anna, Leehr, Elisabeth J., Meinert, Susanne, Stein, Frederike, Teutenberg, Lea, Thomas-Odenthal, Florian, Usemann, Paula, Hermesdorf, Marco, Jamalabadi, Hamidreza, Jansen, Andreas, Nenadic, Igor, Straube, Benjamin, Kircher, Tilo, Berger, Klaus, Risse, Benjamin, Dannlowski, Udo, and Hahn, Tim

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Voxel-based Morphometry (VBM) has emerged as a powerful approach in neuroimaging research, utilized in over 7,000 studies since the year 2000. Using Magnetic Resonance Imaging (MRI) data, VBM assesses variations in the local density of brain tissue and examines its associations with biological and psychometric variables. Here, we present deepmriprep, a neural network-based pipeline that performs all necessary preprocessing steps for VBM analysis of T1-weighted MR images using deep neural networks. Utilizing the Graphics Processing Unit (GPU), deepmriprep is 37 times faster than CAT12, the leading VBM preprocessing toolbox. The proposed method matches CAT12 in accuracy for tissue segmentation and image registration across more than 100 datasets and shows strong correlations in VBM results. Tissue segmentation maps from deepmriprep have over 95% agreement with ground truth maps, and its non-linear registration, using supervised SYMNet, predicts smooth deformation fields comparable to CAT12. The high processing speed of deepmriprep enables rapid preprocessing of extensive datasets and thereby fosters the application of VBM analysis to large-scale neuroimaging studies and opens the door to real-time applications. Finally, deepmripreps straightforward, modular design enables researchers to easily understand, reuse, and advance the underlying methods, fostering further advancements in neuroimaging research. deepmriprep can be conveniently installed as a Python package and is publicly accessible at https://github.com/wwu-mmll/deepmriprep.

Published
2024

2. Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction

Author

Schormair, Barbara, Zhao, Chen, Bell, Steven, Didriksen, Maria, Nawaz, Muhammad S., Schandra, Nathalie, Stefani, Ambra, Högl, Birgit, Dauvilliers, Yves, Bachmann, Cornelius G., Kemlink, David, Sonka, Karel, Paulus, Walter, Trenkwalder, Claudia, Oertel, Wolfgang H., Hornyak, Magdolna, Teder-Laving, Maris, Metspalu, Andres, Hadjigeorgiou, Georgios M., Polo, Olli, Fietze, Ingo, Ross, Owen A., Wszolek, Zbigniew K., Ibrahim, Abubaker, Bergmann, Melanie, Kittke, Volker, Harrer, Philip, Dowsett, Joseph, Chenini, Sofiene, Ostrowski, Sisse Rye, Sørensen, Erik, Erikstrup, Christian, Pedersen, Ole B., Topholm Bruun, Mie, Nielsen, Kaspar R., Butterworth, Adam S., Soranzo, Nicole, Ouwehand, Willem H., Roberts, David J., Danesh, John, Burchell, Brendan, Furlotte, Nicholas A., Nandakumar, Priyanka, Earley, Christopher J., Ondo, William G., Xiong, Lan, Desautels, Alex, Perola, Markus, Vodicka, Pavel, Dina, Christian, Stoll, Monika, Franke, Andre, Lieb, Wolfgang, Stewart, Alexandre F. R., Shah, Svati H., Gieger, Christian, Peters, Annette, Rye, David B., Rouleau, Guy A., Berger, Klaus, Stefansson, Hreinn, Ullum, Henrik, Stefansson, Kari, Hinds, David A., Di Angelantonio, Emanuele, Oexle, Konrad, and Winkelmann, Juliane

Published
2024
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3. Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration

Author

Ahmad, Shahzad, Imtiaz, Mohammad Aslam, Mishra, Aniket, Wang, Ruiqi, Herrera-Rivero, Marisol, Bis, Joshua C, Fornage, Myriam, Roshchupkin, Gennady, Hofer, Edith, Logue, Mark, Longstreth, WT, Xia, Rui, Bouteloup, Vincent, Mosley, Thomas, Launer, Lenore J, Khalil, Michael, Kuhle, Jens, Rissman, Robert A, Chene, Genevieve, Dufouil, Carole, Djoussé, Luc, Lyons, Michael J, Mukamal, Kenneth J, Kremen, William S, Franz, Carol E, Schmidt, Reinhold, Debette, Stephanie, Breteler, Monique MB, Berger, Klaus, Yang, Qiong, Seshadri, Sudha, Aziz, N Ahmad, Ghanbari, Mohsen, and Ikram, M Arfan

Subjects
Biological Sciences, Genetics, Neurodegenerative, Acquired Cognitive Impairment, Human Genome, Dementia, Neurosciences, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Prevention, Aging, 2.1 Biological and endogenous factors, Neurological, Humans, Genome-Wide Association Study, Neurofilament Proteins, Neurodegenerative Diseases, Genetic Predisposition to Disease, Genetic Loci, Biomarkers, Polymorphism, Single Nucleotide, Male, Female, Alzheimer Disease, Biological sciences, Biomedical and clinical sciences
Abstract

Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aβ-40, Aβ-42, and higher incidence of Alzheimer's disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration.

Published
2024

4. Childhood and adolescence factors and multiple sclerosis: results from the German National Cohort (NAKO)

Author

Holz, Anja, Obi, Nadia, Ahrens, Wolfgang, Berger, Klaus, Bohn, Barbara, Brenner, Hermann, Fischer, Beate, Fricke, Julia, Führer, Amand, Gastell, Sylvia, Greiser, Karin Halina, Harth, Volker, Heise, Jana-Kristin, Holleczek, Bernd, Keil, Thomas, Klett-Tammen, Carolina J., Leitzmann, Michael, Lieb, Wolfgang, Meinke-Franze, Claudia, Michels, Karin B., Mikolajczyk, Rafael, Nimptsch, Katharina, Peters, Annette, Pischon, Tobias, Riedel, Oliver, Schikowski, Tamara, Schipf, Sabine, Schmidt, Börge, Schulze, Matthias B., Stang, Andreas, Hellwig, Kerstin, Riemann-Lorenz, Karin, Heesen, Christoph, and Becher, Heiko

Published
2024
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5. Large-scale assessment of physical activity in a population using high-resolution hip-worn accelerometry: the German National Cohort (NAKO)

Author

Weber, Andrea, van Hees, Vincent T., Stein, Michael J., Gastell, Sylvia, Steindorf, Karen, Herbolsheimer, Florian, Ostrzinski, Stefan, Pischon, Tobias, Brandes, Mirko, Krist, Lilian, Marschollek, Michael, Greiser, Karin Halina, Nimptsch, Katharina, Brandes, Berit, Jochem, Carmen, Sedlmeier, Anja M., Berger, Klaus, Brenner, Hermann, Buck, Christoph, Castell, Stefanie, Dörr, Marcus, Emmel, Carina, Fischer, Beate, Flexeder, Claudia, Harth, Volker, Hebestreit, Antje, Heise, Jana-Kristin, Holleczek, Bernd, Keil, Thomas, Koch-Gallenkamp, Lena, Lieb, Wolfgang, Meinke-Franze, Claudia, Michels, Karin B., Mikolajczyk, Rafael, Kluttig, Alexander, Obi, Nadia, Peters, Annette, Schmidt, Börge, Schipf, Sabine, Schulze, Matthias B., Teismann, Henning, Waniek, Sabina, Willich, Stefan N., Leitzmann, Michael F., and Baurecht, Hansjörg

Published
2024
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7. From Group-Differences to Single-Subject Probability: Conformal Prediction-based Uncertainty Estimation for Brain-Age Modeling

Author

Ernsting, Jan, Winter, Nils R., Leenings, Ramona, Sarink, Kelvin, Barkhau, Carlotta B. C., Fisch, Lukas, Emden, Daniel, Holstein, Vincent, Repple, Jonathan, Grotegerd, Dominik, Meinert, Susanne, Investigators, NAKO, Berger, Klaus, Risse, Benjamin, Dannlowski, Udo, and Hahn, Tim

Subjects
Computer Science - Machine Learning
Abstract

The brain-age gap is one of the most investigated risk markers for brain changes across disorders. While the field is progressing towards large-scale models, recently incorporating uncertainty estimates, no model to date provides the single-subject risk assessment capability essential for clinical application. In order to enable the clinical use of brain-age as a biomarker, we here combine uncertainty-aware deep Neural Networks with conformal prediction theory. This approach provides statistical guarantees with respect to single-subject uncertainty estimates and allows for the calculation of an individual's probability for accelerated brain-aging. Building on this, we show empirically in a sample of N=16,794 participants that 1. a lower or comparable error as state-of-the-art, large-scale brain-age models, 2. the statistical guarantees regarding single-subject uncertainty estimation indeed hold for every participant, and 3. that the higher individual probabilities of accelerated brain-aging derived from our model are associated with Alzheimer's Disease, Bipolar Disorder and Major Depressive Disorder., Comment: arXiv admin note: text overlap with arXiv:2107.07977

Published
2023

10. An Uncertainty-Aware, Shareable and Transparent Neural Network Architecture for Brain-Age Modeling

Author

Hahn, Tim, Ernsting, Jan, Winter, Nils R., Holstein, Vincent, Leenings, Ramona, Beisemann, Marie, Fisch, Lukas, Sarink, Kelvin, Emden, Daniel, Opel, Nils, Redlich, Ronny, Repple, Jonathan, Grotegerd, Dominik, Meinert, Susanne, Hirsch, Jochen G., Niendorf, Thoralf, Endemann, Beate, Bamberg, Fabian, Kröncke, Thomas, Bülow, Robin, Völzke, Henry, von Stackelberg, Oyunbileg, Sowade, Ramona Felizitas, Umutlu, Lale, Schmidt, Börge, Caspers, Svenja, Consortium, German National Cohort Study Center, Kugel, Harald, Kircher, Tilo, Risse, Benjamin, Gaser, Christian, Cole, James H., Dannlowski, Udo, and Berger, Klaus

Subjects
Computer Science - Machine Learning, Quantitative Biology - Populations and Evolution
Abstract

The deviation between chronological age and age predicted from neuroimaging data has been identified as a sensitive risk-marker of cross-disorder brain changes, growing into a cornerstone of biological age-research. However, Machine Learning models underlying the field do not consider uncertainty, thereby confounding results with training data density and variability. Also, existing models are commonly based on homogeneous training sets, often not independently validated, and cannot be shared due to data protection issues. Here, we introduce an uncertainty-aware, shareable, and transparent Monte-Carlo Dropout Composite-Quantile-Regression (MCCQR) Neural Network trained on N=10,691 datasets from the German National Cohort. The MCCQR model provides robust, distribution-free uncertainty quantification in high-dimensional neuroimaging data, achieving lower error rates compared to existing models across ten recruitment centers and in three independent validation samples (N=4,004). In two examples, we demonstrate that it prevents spurious associations and increases power to detect accelerated brain-aging. We make the pre-trained model publicly available.

Published
2021

12. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.

Author

Mullins, Niamh, Kang, JooEun, Campos, Adrian I, Coleman, Jonathan RI, Edwards, Alexis C, Galfalvy, Hanga, Levey, Daniel F, Lori, Adriana, Shabalin, Andrey, Starnawska, Anna, Su, Mei-Hsin, Watson, Hunna J, Adams, Mark, Awasthi, Swapnil, Gandal, Michael, Hafferty, Jonathan D, Hishimoto, Akitoyo, Kim, Minsoo, Okazaki, Satoshi, Otsuka, Ikuo, Ripke, Stephan, Ware, Erin B, Bergen, Andrew W, Berrettini, Wade H, Bohus, Martin, Brandt, Harry, Chang, Xiao, Chen, Wei J, Chen, Hsi-Chung, Crawford, Steven, Crow, Scott, DiBlasi, Emily, Duriez, Philibert, Fernández-Aranda, Fernando, Fichter, Manfred M, Gallinger, Steven, Glatt, Stephen J, Gorwood, Philip, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A, Hwu, Hai-Gwo, Jain, Sonia, Jamain, Stéphane, Jiménez-Murcia, Susana, Johnson, Craig, Kaplan, Allan S, Kaye, Walter H, Keel, Pamela K, Kennedy, James L, Klump, Kelly L, Li, Dong, Liao, Shih-Cheng, Lieb, Klaus, Lilenfeld, Lisa, Liu, Chih-Min, Magistretti, Pierre J, Marshall, Christian R, Mitchell, James E, Monson, Eric T, Myers, Richard M, Pinto, Dalila, Powers, Abigail, Ramoz, Nicolas, Roepke, Stefan, Rozanov, Vsevolod, Scherer, Stephen W, Schmahl, Christian, Sokolowski, Marcus, Strober, Michael, Thornton, Laura M, Treasure, Janet, Tsuang, Ming T, Witt, Stephanie H, Woodside, D Blake, Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Air, Tracy M, Alda, Martin, Alfredsson, Lars, Andreassen, Ole A, Anjorin, Adebayo, Appadurai, Vivek, Soler Artigas, María, Van der Auwera, Sandra, Azevedo, M Helena, Bass, Nicholas, Bau, Claiton HD, Baune, Bernhard T, Bellivier, Frank, Berger, Klaus, Biernacka, Joanna M, Bigdeli, Tim B, Binder, Elisabeth B, Boehnke, Michael, Boks, Marco P, Bosch, Rosa, and Braff, David L

Subjects
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Eating Disorders Working Group of the Psychiatric Genomics Consortium, German Borderline Genomics Consortium, MVP Suicide Exemplar Workgroup, VA Million Veteran Program, Humans, Risk Factors, Suicide, Attempted, Mental Disorders, Depressive Disorder, Major, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic correlation, Genome-wide association study, Pleiotropy, Polygenicity, Suicide, Suicide attempt, Human Genome, Behavioral and Social Science, Mental Health, Prevention, Genetics, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundSuicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.MethodsWe conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.ResultsTwo loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.ConclusionsOur results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

Published
2022

13. Predicting brain-age from raw T 1 -weighted Magnetic Resonance Imaging data using 3D Convolutional Neural Networks

Author

Fisch, Lukas, Ernsting, Jan, Winter, Nils R., Holstein, Vincent, Leenings, Ramona, Beisemann, Marie, Sarink, Kelvin, Emden, Daniel, Opel, Nils, Redlich, Ronny, Repple, Jonathan, Grotegerd, Dominik, Meinert, Susanne, Wulms, Niklas, Minnerup, Heike, Hirsch, Jochen G., Niendorf, Thoralf, Endemann, Beate, Bamberg, Fabian, Kröncke, Thomas, Peters, Annette, Bülow, Robin, Völzke, Henry, von Stackelberg, Oyunbileg, Sowade, Ramona Felizitas, Umutlu, Lale, Schmidt, Börge, Caspers, Svenja, Consortium, German National Cohort Study Center, Kugel, Harald, Baune, Bernhard T., Kircher, Tilo, Risse, Benjamin, Dannlowski, Udo, Berger, Klaus, and Hahn, Tim

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Age prediction based on Magnetic Resonance Imaging (MRI) data of the brain is a biomarker to quantify the progress of brain diseases and aging. Current approaches rely on preparing the data with multiple preprocessing steps, such as registering voxels to a standardized brain atlas, which yields a significant computational overhead, hampers widespread usage and results in the predicted brain-age to be sensitive to preprocessing parameters. Here we describe a 3D Convolutional Neural Network (CNN) based on the ResNet architecture being trained on raw, non-registered T$_ 1$-weighted MRI data of N=10,691 samples from the German National Cohort and additionally applied and validated in N=2,173 samples from three independent studies using transfer learning. For comparison, state-of-the-art models using preprocessed neuroimaging data are trained and validated on the same samples. The 3D CNN using raw neuroimaging data predicts age with a mean average deviation of 2.84 years, outperforming the state-of-the-art brain-age models using preprocessed data. Since our approach is invariant to preprocessing software and parameter choices, it enables faster, more robust and more accurate brain-age modeling.

Published
2021

14. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author

Han, Laura KM, Dinga, Richard, Hahn, Tim, Ching, Christopher RK, Eyler, Lisa T, Aftanas, Lyubomir, Aghajani, Moji, Aleman, André, Baune, Bernhard T, Berger, Klaus, Brak, Ivan, Filho, Geraldo Busatto, Carballedo, Angela, Connolly, Colm G, Couvy-Duchesne, Baptiste, Cullen, Kathryn R, Dannlowski, Udo, Davey, Christopher G, Dima, Danai, Duran, Fabio LS, Enneking, Verena, Filimonova, Elena, Frenzel, Stefan, Frodl, Thomas, Fu, Cynthia HY, Godlewska, Beata R, Gotlib, Ian H, Grabe, Hans J, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Hall, Geoffrey B, Harrison, Ben J, Hatton, Sean N, Hermesdorf, Marco, Hickie, Ian B, Ho, Tiffany C, Hosten, Norbert, Jansen, Andreas, Kähler, Claas, Kircher, Tilo, Klimes-Dougan, Bonnie, Krämer, Bernd, Krug, Axel, Lagopoulos, Jim, Leenings, Ramona, MacMaster, Frank P, MacQueen, Glenda, McIntosh, Andrew, McLellan, Quinn, McMahon, Katie L, Medland, Sarah E, Mueller, Bryon A, Mwangi, Benson, Osipov, Evgeny, Portella, Maria J, Pozzi, Elena, Reneman, Liesbeth, Repple, Jonathan, Rosa, Pedro GP, Sacchet, Matthew D, Sämann, Philipp G, Schnell, Knut, Schrantee, Anouk, Simulionyte, Egle, Soares, Jair C, Sommer, Jens, Stein, Dan J, Steinsträter, Olaf, Strike, Lachlan T, Thomopoulos, Sophia I, van Tol, Marie-José, Veer, Ilya M, Vermeiren, Robert RJM, Walter, Henrik, van der Wee, Nic JA, van der Werff, Steven JA, Whalley, Heather, Winter, Nils R, Wittfeld, Katharina, Wright, Margaret J, Wu, Mon-Ju, Völzke, Henry, Yang, Tony T, Zannias, Vasileios, de Zubicaray, Greig I, Zunta-Soares, Giovana B, Abé, Christoph, Alda, Martin, Andreassen, Ole A, Bøen, Erlend, Bonnin, Caterina M, Canales-Rodriguez, Erick J, Cannon, Dara, Caseras, Xavier, Chaim-Avancini, Tiffany M, Elvsåshagen, Torbjørn, Favre, Pauline, Foley, Sonya F, and Fullerton, Janice M

Subjects
Depression, Aging, Brain Disorders, Biomedical Imaging, Serious Mental Illness, Mental Health, Major Depressive Disorder, Behavioral and Social Science, Clinical Research, Neurosciences, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Adolescent, Adult, Aged, Brain, Depressive Disorder, Major, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

Published
2021

21. Biological sex classification with structural MRI data shows increased misclassification in transgender women

Author

Flint, Claas, Förster, Katharina, Koser, Sophie A., Konrad, Carsten, Zwitserlood, Pienie, Berger, Klaus, Hermesdorf, Marco, Kircher, Tilo, Nenadic, Igor, Krug, Axel, Baune, Bernhard T., Dohm, Katharina, Redlich, Ronny, Opel, Nils, Arolt, Volker, Hahn, Tim, Jiang, Xiaoyi, Dannlowski, Udo, and Grotegerd, Dominik

Subjects
Quantitative Biology - Neurons and Cognition, Computer Science - Computer Vision and Pattern Recognition
Abstract

Transgender individuals (TIs) show brain structural alterations that differ from their biological sex as well as their perceived gender. To substantiate evidence that the brain structure of TIs differs from male and female, we use a combined multivariate and univariate approach. Gray matter segments resulting from voxel-based morphometry preprocessing of $N = 1753$ cisgender (CG) healthy participants were used to train ($N=1402$) and validate (20 % hold-out; $N = 351$) a support-vector machine classifying the biological sex. As a second validation, we classified $N = 1104$ patients with depression. A third validation was performed using the matched CG sample of the transgender women (TWs) application-sample. Subsequently, the classifier was applied to $N = 26$ TWs. Finally, we compared brain volumes of CG-men, women and TW-pre/post treatment (cross-sex hormone treatment) in a univariate analysis controlling for sexual orientation, age and total brain volume. The application of our biological sex classifier to the transgender sample resulted in a significantly lower true positive rate (TPR) (TPR-male = 56.0 %). The TPR did not differ between CG-individuals with (TPR-male = 86.9 %) and without depression (TPR-male = 88.5 %). The univariate analysis of the transgender application-sample revealed that TW-pre/post treatment show brain structural differences from CG-women and CG-men in the putamen and insula, as well as the whole-brain analysis. Our results support the hypothesis that brain structure in TW differs from brain structure of their biological sex (male) as well as their perceived gender (female). This finding substantiates evidence that TIs show specific brain structural alterations leading to a different pattern of brain structure than CG-individuals., Comment: Content adapted to the publication at Neuropsychopharmacology

Published
2019
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22. Framework and baseline examination of the German National Cohort (NAKO)

Author

Peters, Annette, Peters, Annette, Greiser, Karin Halina, Göttlicher, Susanne, Ahrens, Wolfgang, Albrecht, Maren, Bamberg, Fabian, Bärnighausen, Till, Becher, Heiko, Berger, Klaus, Beule, Achim, Boeing, Heiner, Bohn, Barbara, Bohnert, Kerstin, Braun, Bettina, Brenner, Hermann, Bülow, Robin, Castell, Stefanie, Damms-Machado, Antje, Dörr, Marcus, Ebert, Nina, Ecker, Margit, Emmel, Carina, Fischer, Beate, Franzke, Claus-Werner, Gastell, Sylvia, Giani, Guido, Günther, Matthias, Günther, Kathrin, Günther, Klaus-Peter, Haerting, Johannes, Haug, Ulrike, Heid, Iris M., Heier, Margit, Heinemeyer, Diana, Hendel, Thomas, Herbolsheimer, Florian, Hirsch, Jochen, Hoffmann, Wolfgang, Holleczek, Bernd, Hölling, Heike, Hörlein, Andreas, Jöckel, Karl-Heinz, Kaaks, Rudolf, Karch, André, Karrasch, Stefan, Kartschmit, Nadja, Kauczor, Hans-Ulrich, Keil, Thomas, Kemmling, Yvonne, Klee, Bianca, Klüppelholz, Birgit, Kluttig, Alexander, Kofink, Lisa, Köttgen, Anna, Kraft, Daniel, Krause, Gérard, Kretz, Lisa, Krist, Lilian, Kühnisch, Jan, Kuß, Oliver, Legath, Nicole, Lehnich, Anna-Therese, Leitzmann, Michael, Lieb, Wolfgang, Linseisen, Jakob, Loeffler, Markus, Macdonald, Anke, Maier-Hein, Klaus H., Mangold, Nina, Meinke-Franze, Claudia, Meisinger, Christa, Melzer, Juliane, Mergarten, Björn, Michels, Karin B., Mikolajczyk, Rafael, Moebus, Susanne, Mueller, Ulrich, Nauck, Matthias, Niendorf, Thoralf, Nikolaou, Konstantin, Obi, Nadia, Ostrzinski, Stefan, Panreck, Leo, Pigeot, Iris, Pischon, Tobias, Pschibul-Thamm, Irene, Rathmann, Wolfgang, Reineke, Achim, Roloff, Stefanie, Rujescu, Dan, Rupf, Stefan, Sander, Oliver, Schikowski, Tamara, Schipf, Sabine, Schirmacher, Peter, Schlett, Christopher L., Schmidt, Börge, Schmidt, Georg, Schmidt, Martin, Schöne, Gina, Schulz, Holger, Schulze, Matthias B., Schweig, Alexandra, Sedlmeier, Anja M., Selder, Sonja, Six-Merker, Julia, Sowade, Ramona, Stang, Andreas, Stegle, Oliver, Steindorf, Karen, Stübs, Gunthard, Swart, Enno, Teismann, Henning, Thiele, Inke, Thierry, Sigrid, Ueffing, Marius, Völzke, Henry, Waniek, Sabina, Weber, Andrea, Werner, Nicole, Wichmann, H.-Erich, Willich, Stefan N., Wirkner, Kerstin, Wolf, Kathrin, Wolff, Robert, Zeeb, Hajo, Zinkhan, Melanie, and Zschocke, Johannes

Published
2022
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24. GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores

Author

Mullins, Niamh, Bigdeli, Tim B, Børglum, Anders D, Coleman, Jonathan RI, Demontis, Ditte, Mehta, Divya, Power, Robert A, Ripke, Stephan, Stahl, Eli A, Starnawska, Anna, Anjorin, Adebayo, Corvin, Aiden, Sanders, Alan R, Forstner, Andreas J, Reif, Andreas, Koller, Anna C, Świątkowska, Beata, Baune, Bernhard T, Müller-Myhsok, Bertram, Penninx, Brenda WJH, Pato, Carlos, Zai, Clement, Rujescu, Dan, Hougaard, David M, Quested, Digby, Levinson, Douglas F, Binder, Elisabeth B, Byrne, Enda M, Agerbo, Esben, Streit, Fabian, Mayoral, Fermin, Bellivier, Frank, Degenhardt, Franziska, Breen, Gerome, Morken, Gunnar, Turecki, Gustavo, Rouleau, Guy A, Grabe, Hans J, Völzke, Henry, Jones, Ian, Giegling, Ina, Agartz, Ingrid, Melle, Ingrid, Lawrence, Jacob, Walters, James TR, Strohmaier, Jana, Shi, Jianxin, Hauser, Joanna, Biernacka, Joanna M, Vincent, John B, Kelsoe, John, Strauss, John S, Lissowska, Jolanta, Pimm, Jonathan, Smoller, Jordan W, Guzman-Parra, José, Berger, Klaus, Scott, Laura J, Jones, Lisa A, Azevedo, M Helena, Trzaskowski, Maciej, Kogevinas, Manolis, Rietschel, Marcella, Boks, Marco, Ising, Marcus, Grigoroiu-Serbanescu, Maria, Hamshere, Marian L, Leboyer, Marion, Frye, Mark, Nöthen, Markus M, Alda, Martin, Preisig, Martin, Nordentoft, Merete, Boehnke, Michael, O’Donovan, Michael C, Owen, Michael J, Pato, Michele T, Renteria, Miguel E, Budde, Monika, Weissman, Myrna M, Wray, Naomi R, Bass, Nicholas, Craddock, Nicholas, Smeland, Olav B, Andreassen, Ole A, Mors, Ole, Gejman, Pablo V, Sklar, Pamela, McGrath, Patrick, Hoffmann, Per, McGuffin, Peter, Lee, Phil H, Mortensen, Preben Bo, Kahn, René S, Ophoff, Roel A, Adolfsson, Rolf, Van der Auwera, Sandra, Djurovic, Srdjan, Kloiber, Stefan, and Heilmann-Heimbach, Stefanie

Subjects
Prevention, Suicide, Serious Mental Illness, Schizophrenia, Human Genome, Depression, Mental Health, Genetics, Brain Disorders, Aetiology, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Bipolar Disorder, Case-Control Studies, Depressive Disorder, Major, Female, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Risk Factors, Suicide, Attempted, M.R.C.Psych, Dr.Med.Sc, Dipl.-Psych, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Mood Disorders, Polygenic Risk Scoring, Psychiatric Genomics Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveMore than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.MethodsThe samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.ResultsThree genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).ConclusionsThis study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

Published
2019

27. Borrelia multiplex: a bead-based multiplex assay for the simultaneous detection of Borrelia specific IgG/IgM class antibodies

Author

Häring, Julia, Hassenstein, Max J., Becker, Matthias, Ortmann, Julia, Junker, Daniel, Karch, André, Berger, Klaus, Tchitchagua, Tatia, Leschnik, Olaf, Harries, Manuela, Gornyk, Daniela, Hernández, Pilar, Lange, Berit, Castell, Stefanie, Krause, Gérard, Dulovic, Alex, Strengert, Monika, and Schneiderhan-Marra, Nicole

Published
2022
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28. Identifying the Common Genetic Basis of Antidepressant Response

Author

Kasper, Siegfried, Zohar, Joseph, Souery, Daniel, Montgomery, Stuart, Albani, Diego, Forloni, Gianluigi, Ferentinos, Panagiotis, Rujescu, Dan, Mendlewicz, Julien, Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R.I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E.J.C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M., O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Pain, Oliver, Hodgson, Karen, Marshe, Victoria S., Campos, Adrian I., Carrillo-Roa, Tania, Cattaneo, Annamaria, Als, Thomas D., Dernovsek, Mojca Z., Fabbri, Chiara, Henigsberg, Neven, Hauser, Joanna, Kennedy, James L., Lenze, Eric J., Müller, Daniel J., Mulsant, Benoit H., Perroud, Nader, Rentería, Miguel E., Reynolds, Charles F., III, Wigmore, Eleanor M., Aitchison, Katherine J., Biernacka, Joanna M., Bondolfi, Guido, Kato, Masaki, Liu, Yu-Li, Serretti, Alessandro, Tsai, Shih-Jen, Turecki, Gustavo, and Weinshilboum, Richard

Published
2022
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29. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study

Author

Aeschbacher, Stefanie, Barakovic, Muhamed, Buser, Andreas, Chan, Andrew, Disanto, Giulio, D'Souza, Marcus, Du Pasquier, Renaud, Findling, Oliver, Galbusera, Riccardo, Hrusovsky, Kevin, Khalil, Michael, Lorscheider, Johannes, Mathias, Amandine, Orleth, Annette, Radue, Ernst-Wilhelm, Rahmanzadeh, Reza, Sinnecker, Tim, Subramaniam, Suvitha, Vehoff, Jochen, Wellmann, Sven, Wuerfel, Jens, Zecca, Chiara, Benkert, Pascal, Meier, Stephanie, Schaedelin, Sabine, Manouchehrinia, Ali, Yaldizli, Özgür, Maceski, Aleksandra, Oechtering, Johanna, Achtnichts, Lutz, Conen, David, Derfuss, Tobias, Lalive, Patrice H, Mueller, Christian, Müller, Stefanie, Naegelin, Yvonne, Oksenberg, Jorge R, Pot, Caroline, Salmen, Anke, Willemse, Eline, Kockum, Ingrid, Blennow, Kaj, Zetterberg, Henrik, Gobbi, Claudio, Kappos, Ludwig, Wiendl, Heinz, Berger, Klaus, Sormani, Maria Pia, Granziera, Cristina, Piehl, Fredrik, Leppert, David, and Kuhle, Jens

Published
2022
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30. Results of the prospective multicenter SoLKiD cohort study indicate bio-psycho-social outcome risks to kidney donors 12 months after donation

Author

Koch, Martina, Kröncke, Sylvia, Weimer, Rolf, Rainer, Lucy, Sommerer, Claudia, Zeier, Martin, Budde, Klemens, Halleck, Fabian, Ivens, Katrin, Hansen, Anita, Reinke, Petra, Pascher, Andreas, Mühlfeld, Anja, Floege, Jürgen, Wahba, Roger, Vitinius, Frank, Kribben, Andreas, Eisenberger, Ute, Hugo, Christian, Quick, Carmen, Nitschke, Martin, Derad, Inge, Rath, Thomas, Mönch, Christian, Schiffer, Mario, Güler, Faikal, Krüger, Bernd, Bönnighoff, Roderich, Hauser, Ingeborg, Platschek, Steffen, Lopau, Kai, Pein, Ulrich, Weigand, Karl, Feldkamp, Thorsten, Kunzendorf, Ulrich, Suwelack, Barbara, Berger, Klaus, Wolters, Heiner, Gerß, Joachim W.O., Bormann, Eike, Wörmann, Viktorya, and Burgmer, Markus

Published
2022
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31. Mental health of individuals with pre-existing mental illnesses at the beginning of the COVID-19 pandemic: results of the German National Cohort (NAKO).

Author

Stein, Janine, Pabst, Alexander, Berger, Klaus, Karch, André, Teismann, Henning, Streit, Fabian, Grabe, Hans J., Mikolajczyk, Rafael, Massag, Janka, Lieb, Wolfgang, Castell, Stefanie, Heise, Jana-Kristin, Schulze, Matthias B., Gastell, Sylvia, Harth, Volker, Obi, Nadia, Peters, Annette, Huemer, Marie-Theres, Bohmann, Patricia, and Leitzmann, Michael

Published
2024
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32. Genome-wide interaction study with major depression identifies novel variants associated with cognitive function

Author

Thalamuthu, Anbupalam, Mills, Natalie T., Berger, Klaus, Minnerup, Heike, Grotegerd, Dominik, Dannlowski, Udo, Meinert, Susanne, Opel, Nils, Repple, Jonathan, Gruber, Marius, Nenadić, Igor, Stein, Frederike, Brosch, Katharina, Meller, Tina, Pfarr, Julia-Katharina, Forstner, Andreas J., Hoffmann, Per, Nöthen, Markus M., Witt, Stephanie, Rietschel, Marcella, Kircher, Tilo, Adams, Mark, McIntosh, Andrew M., Porteous, David J., Deary, Ian J., Hayward, Caroline, Campbell, Archie, Grabe, Hans Jörgen, Teumer, Alexander, Homuth, Georg, van der Auwera-Palitschka, Sandra, Oliver Schubert, K., and Baune, Bernhard T.

Published
2022
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34. Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders: Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group

Author

Opel, Nils, Thalamuthu, Anbupalam, Milaneschi, Yuri, Grotegerd, Dominik, Flint, Claas, Leenings, Ramona, Goltermann, Janik, Richter, Maike, Hahn, Tim, Woditsch, Georg, Berger, Klaus, Hermesdorf, Marco, McIntosh, Andrew, Whalley, Heather C., Harris, Mathew A., MacMaster, Frank P., Walter, Henrik, Veer, Ilya M., Frodl, Thomas, Carballedo, Angela, Krug, Axel, Nenadic, Igor, Kircher, Tilo, Aleman, Andre, Groenewold, Nynke A., Stein, Dan J., Soares, Jair C., Zunta-Soares, Giovana B., Mwangi, Benson, Wu, Mon-Ju, Walter, Martin, Li, Meng, Harrison, Ben J., Davey, Christopher G., Cullen, Kathryn R., Klimes-Dougan, Bonnie, Mueller, Bryon A., Sämann, Philipp G., Penninx, Brenda, Nawijn, Laura, Veltman, Dick J., Aftanas, Lyubomir, Brak, Ivan V., Filimonova, Elena A., Osipov, Evgeniy A., Reneman, Liesbeth, Schrantee, Anouk, Grabe, Hans J., Van der Auwera, Sandra, Wittfeld, Katharina, Hosten, Norbert, Völzke, Henry, Sim, Kang, Gotlib, Ian H., Sacchet, Matthew D., Lagopoulos, Jim, Hatton, Sean N., Hickie, Ian, Pozzi, Elena, Thompson, Paul M., Jahanshad, Neda, Schmaal, Lianne, Baune, Bernhard T., and Dannlowski, Udo

Published
2021
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36. The association between genetically determined ABO blood types and major depressive disorder

Author

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, Preisig, Martin, Rietschel, Marcella, Shi, Jianxin, Smoller, Jordan W, Tiemeier, Henning, Uher, Rudolf, Völker, Uwe, Völzke, Henry, Weissman, Myrna M, Grabe, Hans J, and Van der Auwera, Sandra

Published
2021
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37. A genome-wide association study meta-analysis in a European sample of stage III/IV grade C periodontitis patients ≤35 years of age identifies new risk loci

Author

De Almeida, Silvia Diz, Richter, Gesa M., de Coo, Alicia, Jepsen, Soren, Kapferer-Seebacher, Ines, Dommisch, Henrik, Berger, Klaus, Laudes, Matthias, Lieb, Wolfgang, Loos, Bruno G., van Der Velde, Nathalie, van Schoor, Natasja, de Groot, Lisette, Blanco, Juan, Carracedo, Angel, Cruz, Raquel, Schaefer, Arne S., De Almeida, Silvia Diz, Richter, Gesa M., de Coo, Alicia, Jepsen, Soren, Kapferer-Seebacher, Ines, Dommisch, Henrik, Berger, Klaus, Laudes, Matthias, Lieb, Wolfgang, Loos, Bruno G., van Der Velde, Nathalie, van Schoor, Natasja, de Groot, Lisette, Blanco, Juan, Carracedo, Angel, Cruz, Raquel, and Schaefer, Arne S.

Abstract

Aim: Few genome-wide association studies (GWAS) have been conducted for severe forms of periodontitis (stage III/IV grade C), and the number of known risk genes is scarce. To identify further genetic risk variants to improve the understanding of the disease aetiology, a GWAS meta-analysis in cases with a diagnosis at <= 35 years of age was performed. Materials and Methods: Genotypes from German, Dutch and Spanish GWAS studies of III/IV-C periodontitis diagnosed at age <= 35 years were imputed using TopMed. After quality control, a meta-analysis was conducted on 8,666,460 variants in 1306 cases and 7817 controls with METAL. Variants were prioritized using FUMA for gene-based tests, functional annotation and a transcriptome-wide association study integrating eQTL data. Results: The study identified a novel genome-wide significant association in the FCER1G gene (p = 1.0 x 10(-9)), which was previously suggestively associated with III/IV-C periodontitis. Six additional genes showed suggestive association with p < 10(-5), including the known risk gene SIGLEC5. HMCN2 showed the second strongest association in this study (p = 6.1 x 10(-8)). Conclusions: This study expands the set of known genetic loci for severe periodontitis with an age of onset <= 35 years. The putative functions ascribed to the associated genes highlight the significance of oral barrier tissue stability, wound healing and tissue regeneration in the aetiology of these periodontitis forms and suggest the importance of tissue regeneration in maintaining oral health.

Published
2024

41. The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls

Author

Byrne, Enda M., Forstner, Andreas J., Holmans, Peter A., de Leeuw, Christiaan A., Mattheisen, Manuel, McQuillin, Andrew, Whitehead Pavlides, Jennifer M., Pers, Tune H., Ripke, Stephan, Stahl, Eli A., Steinberg, Stacy, Trubetskoy, Vassily, Trzaskowski, Maciej, Wang, Yunpeng, Abbott, Liam, Abdellaoui, Abdel, Adams, Mark J., Adolfsson, Annelie Nordin, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D., Andlauer, Till F.M., Anjorin, Adebayo, Antilla, Verneri, Van der Auwera, Sandra, Awasthi, Swapnil, Bacanu, Silviu-Alin, Badner, Judith A., Bækvad-Hansen, Marie, Barchas, Jack D., Bass, Nicholas, Bauer, Michael, Beekman, Aartjan T.F., Belliveau, Richard, Bergen, Sarah E., Bigdeli, Tim B., Binder, Elisabeth B., Bøen, Erlend, Boks, Marco, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Byerley, William, Cai, Na, Casas, Miquel, Castelao, Enrique, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W., Chen, Danfeng, Christensen, Jane Hvarregaard, Churchhouse, Claire, St Clair, David, Clarke, Toni-Kim, Colodro-Conde, Lucía, Coryell, William, Couvy-Duchesne, Baptiste, Craig, David W., Crawford, Gregory E., Cruceanu, Cristiana, Czerski, Piotr M., Dale, Anders M., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Derks, Eske M., Direk, Nese, Djurovic, Srdjan, Dobbyn, Amanda L., Dolan, Conor V., Dumont, Ashley, Dunn, Erin C., Eley, Thalia C., Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Finucane, Hilary K., Fischer, Sascha B., Flickinger, Matthew, Foo, Jerome C., Foroud, Tatiana M., Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Goes, Fernando S., Goldstein, Jaqueline, Gordon, Scott D., Gordon-Smith, Katherine, Green, Elaine K., Green, Melissa J., Greenwood, Tiffany A., Grove, Jakob, Guan, Weihua, Hall, Lynsey S., Hamshere, Marian L., Hansen, Christine Søholm, Hansen, Thomas F., Hautzinger, Martin, Heilbronner, Urs, van Hemert, Albert M., Herms, Stefan, Hickie, Ian B., Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Huckins, Laura, Ising, Marcus, Jamain, Stéphane, Jansen, Rick, Johnson, Jessica S., de Jong, Simone, Jorgenson, Eric, Juréus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L., Hassan Kiadeh, Farnush Farhadi, Kittel-Schneider, Sarah, Knowles, James A., Kogevinas, Manolis, Kohane, Isaac S., Koller, Anna C., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kupka, Ralph, Kutalik, Zoltán, Lavebratt, Catharina, Lawrence, Jacob, Lawson, William B., Leber, Markus, Lee, Phil H., Levy, Shawn E., Li, Jun Z., Li, Yihan, Lind, Penelope A., Liu, Chunyu, Olde Loohuis, Loes M., Maaser, Anna, MacIntyre, Donald J., MacKinnon, Dean F., Mahon, Pamela B., Maier, Wolfgang, Maier, Robert M., Marchini, Jonathan, Martinsson, Lina, Mbarek, Hamdi, McCarroll, Steve, McGrath, Patrick, McGuffin, Peter, McInnis, Melvin G., McKay, James D., Medeiros, Helena, Medland, Sarah E., Mehta, Divya, Meng, Fan, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mirza, Saira Saeed, Mondimore, Francis M., Montgomery, Grant W., Morris, Derek W., Mostafavi, Sara, Mühleisen, Thomas W., Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nguyen, Hoang, Nievergelt, Caroline M., Nivard, Michel G., Nwulia, Evaristus A., Nyholt, Dale R., O'Donovan, Claire, O'Reilly, Paul F., Ori, Anil P.S., Oruc, Lilijana, Ösby, Urban, Oskarsson, Hogni, Painter, Jodie N., Parra, José Guzman, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Perry, Amy, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pfennig, Andrea, Pistis, Giorgio, Purcell, Shaun M., Quiroz, Jorge A., Qvist, Per, Regeer, Eline J., Reif, Andreas, Reinbold, Céline S., Rice, John P., Riley, Brien P., Rivas, Fabio, Rivera, Margarita, Roussos, Panos, Ruderfer, Douglas M., Ryu, Euijung, Sánchez-Mora, Cristina, Schatzberg, Alan F., Scheftner, William A., Schoevers, Robert, Schork, Nicholas J., Schulte, Eva C., Shehktman, Tatyana, Shen, Ling, Shi, Jianxin, Shilling, Paul D., Shyn, Stanley I., Sigurdsson, Engilbert, Slaney, Claire, Smeland, Olav B., Smit, Johannes H., Smith, Daniel J., Sobell, Janet L., Spijker, Anne T., Steffens, Michael, Strauss, John S., Streit, Fabian, Strohmaier, Jana, Szelinger, Szabolcs, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Robert C., Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Uitterlinden, André G., Umbricht, Daniel, Vedder, Helmut, Viktorin, Alexander, Visscher, Peter M., Wang, Weiqing, Watson, Stanley J., Webb, Bradley T., Weickert, Cynthia Shannon, Weickert, Thomas W., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Xu, Wei, Yang, Jian, Young, Allan H., Zandi, Peter, Zhang, Peng, Zhang, Futao, Zollner, Sebastian, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Arolt, Volker, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Berger, Klaus, Berrettini, Wade H., Biernacka, Joanna M., Blackwood, Douglas H.R., Boehnke, Michael, Boomsma, Dorret I., Corvin, Aiden, Craddock, Nicholas, Daly, Mark J., Dannlowski, Udo, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Etain, Bruno, Frye, Mark, Fullerton, Janice M., Gershon, Elliot S., de Geus, E.J.C., Gill, Michael, Goes, Fernando, Grabe, Hans J., Grigoroiu-Serbanescu, Maria, Hamilton, Steven P., Hauser, Joanna, Hayward, Caroline, Heath, Andrew C., Hougaard, David M., Hultman, Christina M., Jones, Ian, Jones, Lisa A., Kahn, René S., Kendler, Kenneth S., Kirov, George, Kloiber, Stefan, Landén, Mikael, Leboyer, Marion, Lewis, Glyn, Li, Qingqin S., Lissowska, Jolanta, Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Metspalu, Andres, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nimgaonkar, Vishwajit, Nordentoft, Merete, Nöthen, Markus M., O'Donovan, Michael C., Oedegaard, Ketil J., Owen, Michael J., Paciga, Sara A., Pato, Carlos, Pato, Michele T., Pedersen, Nancy L., Penninx, Brenda W.J. H., Perlis, Roy H., Porteous, David J., Posthuma, Danielle, Potash, James B., Preisig, Martin, Ramos-Quiroga, Josep Antoni, Ribasés, Marta, Rietschel, Marcella, Rouleau, Guy A., Schaefer, Catherine, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Serretti, Alessandro, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Tiemeier, Henning, Turecki, Gustavo, Uher, Rudolf, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Andreassen, Ole A., Børglum, Anders D., Cichon, Sven, Edenberg, Howard J., Di Florio, Arianna, Kelsoe, John, Levinson, Douglas F., Lewis, Cathryn M., Nurnberger, John I., Ophoff, Roel A., Scott, Laura J., Sklar, Pamela, Sullivan, Patrick F., Wray, Naomi R., Coleman, Jonathan R.I., Gaspar, Héléna A., Bryois, Julien, and Breen, Gerome

Published
2020
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42. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Author

Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R.I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andrés G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, EJC., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela AF., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M., O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Glanville, Kylie P., Hanscombe, Ken B., Euesden, Jack, Choi, Shing Wan, Purves, Kirstin L., Blackwood, Douglas H.R., and de Geus, Eco J.C.

Published
2020
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43. Childhood trauma and somatic and mental illness in adulthood—findings of the NAKO health study

Author

Klinger-König, Johanna, primary, Erhardt, Angelika, additional, Streit, Fabian, additional, Völker, Maja P., additional, Schulze, Matthias B., additional, Keil, Thomas, additional, Fricke, Julia, additional, Castell, Stefanie, additional, Klett-Tammen, Carolina J., additional, Pischon, Tobias, additional, Karch, André, additional, Teismann, Henning, additional, Michels, Karin B., additional, Greiser, K. Halina, additional, Becher, Heiko, additional, Karrasch, Stefan, additional, Ahrens, Wolfgang, additional, Meinke-Franze, Claudia, additional, Schipf, Sabine, additional, Mikolajczyk, Rafael, additional, Führer, Amand, additional, Brandes, Berit, additional, Schmidt, Börge, additional, Emmel, Carina, additional, Leitzmann, Michael, additional, Konzok, Julian, additional, Peters, Anette, additional, Obi, Nadia, additional, Brenner, Hermann, additional, Holleczek, Bernd, additional, Velásquez, Ilais Moreno, additional, Deckert, Jürgen, additional, Baune, Bernhard T., additional, Rietschel, Marcella, additional, Berger, Klaus, additional, and Grabe, Hans J., additional

Published
2024
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44. Replicability and Generalizability of Gray Matter Reductions in Major Depression: A Voxel-Based Investigation of 4021 Individuals

Author

Dannlowski, Udo, primary, Winter, Nils R., additional, Meinert, Susanne, additional, Grotegerd, Dominik, additional, Kraus, Anna, additional, Flinkenflügel, Kira, additional, Leehr, Elisabeth J., additional, Böhnlein, Joscha, additional, Borgers, Tiana, additional, Fisch, Lukas, additional, Bauer, Michael, additional, Pfennig, Andrea, additional, Richter, Maike, additional, Opel, Nils, additional, Repple, Jonathan, additional, Gruber, Marius, additional, Minnerup, Heike, additional, Hermesdorf, Marco, additional, Nitsch, Robert, additional, Groß, Joachim, additional, Jansen, Andreas, additional, Alexander, Nina, additional, Stein, Frederike, additional, Nenadić, Igor, additional, Berger, Klaus, additional, Kircher, Tilo, additional, Hahn, Tim, additional, and Goltermann, Janik, additional

Published
2024
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45. Genome‐wide Association Study Meta‐analysis of Neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration

Author

Ahmad, Shahzad, primary, Imtiaz, Mohammed Aslam, additional, Mishra, Aniket, additional, Wang, Ruiqi, additional, Rivero, Marisol Herrera‐, additional, Bis, Joshua C, additional, Fornage, Myriam, additional, Roshchupkin, Gennady V., additional, Hofer, Edith, additional, Logue, Mark W., additional, Longstreth, W.T., additional, Xia, Rui, additional, Bouteloup, Vincent, additional, Mosley, Thomas H., additional, Launer, Lenore J J., additional, Khalil, Michael, additional, Kuhle, Jens, additional, Rissman, Robert A, additional, Chêne, Geneviève, additional, Dufouil, Carole, additional, Djoussé, Luc, additional, Lyons, Michael J., additional, Mukamal, Kenneth J, additional, Stone, William Seth, additional, Franz, Carol E, additional, Schmidt, Reinhold, additional, Debette, Stéphanie, additional, Breteler, Monique M.B., additional, Berger, Klaus, additional, Yang, Qiong, additional, Seshadri, Sudha, additional, Aziz, N. Ahmad, additional, Ghanbari, Mohsen, additional, and Ikram, M. Arfan, additional

Published
2023
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46. Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity

Author

Becker, Matthias, Strengert, Monika, Junker, Daniel, Kaiser, Philipp D., Kerrinnes, Tobias, Traenkle, Bjoern, Dinter, Heiko, Häring, Julia, Ghozzi, Stéphane, Zeck, Anne, Weise, Frank, Peter, Andreas, Hörber, Sebastian, Fink, Simon, Ruoff, Felix, Dulovic, Alex, Bakchoul, Tamam, Baillot, Armin, Lohse, Stefan, Cornberg, Markus, Illig, Thomas, Gottlieb, Jens, Smola, Sigrun, Karch, André, Berger, Klaus, Rammensee, Hans-Georg, Schenke-Layland, Katja, Nelde, Annika, Märklin, Melanie, Heitmann, Jonas S., Walz, Juliane S., Templin, Markus, Joos, Thomas O., Rothbauer, Ulrich, Krause, Gérard, and Schneiderhan-Marra, Nicole

Published
2021
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47. Restless legs syndrome

Author

Manconi, Mauro, Garcia-Borreguero, Diego, Schormair, Barbara, Videnovic, Aleksandar, Berger, Klaus, Ferri, Raffaele, and Dauvilliers, Yves

Published
2021
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