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63 results on '"Papassotiropoulos, Andreas"'

1. 8th Santorini Conference: Systems medicine and personalized health and therapy, Santorini, Greece, 3-5 October 2016

Author: Visvikis-Siest, Sophie, Aldasoro Arguinano, Alex-Ander, Stathopoulou, Maria, Xie, Ting, Petrelis, Alexandros, Weryha, Georges, Froguel, Philippe, Meier-Abt, Peter, Meyer, Urs A., Mlakar, Vid, Ansari, Marc, Papassotiropoulos, Andreas, Dedoussis, Georges, Pan, Baishen, Bühlmann, Roland P., Noyer-Weidner, Mario, Dietrich, Pierre-Yves, Van Schaik, Ron, Innocenti, Federico, März, Winfried, Bekris, Lynn M., Deloukas, Panos, Visvikis-Siest, Sophie, Aldasoro Arguinano, Alex-Ander, Stathopoulou, Maria, Xie, Ting, Petrelis, Alexandros, Weryha, Georges, Froguel, Philippe, Meier-Abt, Peter, Meyer, Urs A., Mlakar, Vid, Ansari, Marc, Papassotiropoulos, Andreas, Dedoussis, Georges, Pan, Baishen, Bühlmann, Roland P., Noyer-Weidner, Mario, Dietrich, Pierre-Yves, Van Schaik, Ron, Innocenti, Federico, März, Winfried, Bekris, Lynn M., and Deloukas, Panos
Published: 2021

2. NGS-pipe: a flexible, easily extendable and highly configurable framework for NGS analysis

Author: Singer, Jochen, Ruscheweyh, Hans-Joachim, Hofmann, Ariane L., Thurnherr, Thomas, Singer, Franziska, Toussaint, Nora C., Ng, Charlotte K Y., Piscuoglio, Salvatore, Beisel, Christian, Christofori, Gerhard, Dummer, Reinhard, Hall, Michael N., Krek, Wilhelm, Levesque, Mitchell P., Manz, Markus G., Moch, Holger, Papassotiropoulos, Andreas, Stekhoven, Daniel J., Wild, Peter, Wüst, Thomas, Rinn, Bernd, Beerenwinkel, Niko, Berger, Bonnie, Singer, Jochen, Ruscheweyh, Hans-Joachim, Hofmann, Ariane L., Thurnherr, Thomas, Singer, Franziska, Toussaint, Nora C., Ng, Charlotte K Y., Piscuoglio, Salvatore, Beisel, Christian, Christofori, Gerhard, Dummer, Reinhard, Hall, Michael N., Krek, Wilhelm, Levesque, Mitchell P., Manz, Markus G., Moch, Holger, Papassotiropoulos, Andreas, Stekhoven, Daniel J., Wild, Peter, Wüst, Thomas, Rinn, Bernd, Beerenwinkel, Niko, and Berger, Bonnie
Abstract: Motivation Next-generation sequencing is now an established method in genomics, and massive amounts of sequencing data are being generated on a regular basis. Analysis of the sequencing data is typically performed by lab-specific in-house solutions, but the agreement of results from different facilities is often small. General standards for quality control, reproducibility and documentation are missing. Results We developed NGS-pipe, a flexible, transparent and easy-to-use framework for the design of pipelines to analyze whole-exome, whole-genome and transcriptome sequencing data. NGS-pipe facilitates the harmonization of genomic data analysis by supporting quality control, documentation, reproducibility, parallelization and easy adaptation to other NGS experiments. Availability and implementation https://github.com/cbg-ethz/NGS-pipe
Published: 2021

3. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, Kaufmann, Tobias, Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, and Kaufmann, Tobias
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
Published: 2020
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4. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

Author: van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, Westlye, Lars T, van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, and Westlye, Lars T
Abstract: The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
Published: 2020
Full Text: View/download PDF

5. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

Author: van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, Westlye, Lars T, van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, and Westlye, Lars T
Abstract: The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
Published: 2020
Full Text: View/download PDF

6. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
Full Text: View/download PDF

7. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

Author: van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, Westlye, Lars T, van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, and Westlye, Lars T
Abstract: The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
Published: 2020
Full Text: View/download PDF

8. Genetic control of variability in subcortical and intracranial volumes

Author: Córdova-Palomera, Aldo, van der Meer, Dennis, Kaufmann, Tobias, Bettella, Francesco, Wang, Yunpeng, Alnaes, Dag, Doan, Nhat Trung, Agartz, Ingrid, Bertolino, Alessandro, Buitelaar, Jan K., Coynel, David, Djurovic, Srdjan, Dørum, Erlend S., Espeseth, Thomas, Fazio, Leonardo, Franke, Barbara, Frei, Oleksandr, Håberg, Asta, Le Hellard, Stephanie, Jönsson, Erik G., Kolskår, Knut K., Lund, Martina J., Moberget, Torgeir, Nordvik, Jan E., Nyberg, Lars, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique, Rampino, Antonio, Richard, Genevieve, Rokicki, Jaroslav, Sanders, Anne-Marthe, Schwarz, Emanuel, Smeland, Olav B., Steen, Vidar M., Starrfelt, Jostein, Sønderby, Ida E., Ulrichsen, Kristine M., Andreassen, Ole A., Westlye, Lars T., Córdova-Palomera, Aldo, van der Meer, Dennis, Kaufmann, Tobias, Bettella, Francesco, Wang, Yunpeng, Alnaes, Dag, Doan, Nhat Trung, Agartz, Ingrid, Bertolino, Alessandro, Buitelaar, Jan K., Coynel, David, Djurovic, Srdjan, Dørum, Erlend S., Espeseth, Thomas, Fazio, Leonardo, Franke, Barbara, Frei, Oleksandr, Håberg, Asta, Le Hellard, Stephanie, Jönsson, Erik G., Kolskår, Knut K., Lund, Martina J., Moberget, Torgeir, Nordvik, Jan E., Nyberg, Lars, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique, Rampino, Antonio, Richard, Genevieve, Rokicki, Jaroslav, Sanders, Anne-Marthe, Schwarz, Emanuel, Smeland, Olav B., Steen, Vidar M., Starrfelt, Jostein, Sønderby, Ida E., Ulrichsen, Kristine M., Andreassen, Ole A., and Westlye, Lars T.
Abstract: Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.
Published: 2020
Full Text: View/download PDF

9. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
Full Text: View/download PDF

10. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
Full Text: View/download PDF

11. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

Author: Meer, D. van der, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E., Smeland, Olav B., Agartz, I., Bertolino, Alessandro, Bralten, J.B., Brandt, Christine L., Buitelaar, J.K., Djurovic, Srdjan, Donkelaar, M.M.J. van, Dørum, Erlend S., Espeseth, Thomas, Faraone, S.V., Fernandez, G., Fisher, S.E., Franke, B., Haatveit, Beathe, Hartman, C.A., Hoekstra, P.J., Håberg, Asta K., Jönsson, Erik G., Kolskår, Knut K., Le Hellard, Stephanie, Lund, Martina J., Lundervold, Astri J., Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C., Nordvik, Jan E., Nyberg, Lars, Oosterlaan, J., Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J. F., Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, A.N., Steen, Vidar M., Tønnesen, Siren, Ulrichsen, Kristine M., Zwiers, M.P., Andreassen, O.A., Westlye, Lars T., Meer, D. van der, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E., Smeland, Olav B., Agartz, I., Bertolino, Alessandro, Bralten, J.B., Brandt, Christine L., Buitelaar, J.K., Djurovic, Srdjan, Donkelaar, M.M.J. van, Dørum, Erlend S., Espeseth, Thomas, Faraone, S.V., Fernandez, G., Fisher, S.E., Franke, B., Haatveit, Beathe, Hartman, C.A., Hoekstra, P.J., Håberg, Asta K., Jönsson, Erik G., Kolskår, Knut K., Le Hellard, Stephanie, Lund, Martina J., Lundervold, Astri J., Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C., Nordvik, Jan E., Nyberg, Lars, Oosterlaan, J., Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J. F., Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, A.N., Steen, Vidar M., Tønnesen, Siren, Ulrichsen, Kristine M., Zwiers, M.P., Andreassen, O.A., and Westlye, Lars T.
Abstract: Contains fulltext : 199959.pdf (publisher's version ) (Open Access) Contains fulltext : 199959pos.pdf (postprint version ) (Open Access)
Published: 2020

12. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, Kaufmann, Tobias, Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, and Kaufmann, Tobias
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
Published: 2020
Full Text: View/download PDF

13. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

Author: Meer, D. van der, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E., Smeland, Olav B., Agartz, I., Bertolino, Alessandro, Bralten, J.B., Brandt, Christine L., Buitelaar, J.K., Djurovic, Srdjan, Donkelaar, M.M.J. van, Dørum, Erlend S., Espeseth, Thomas, Faraone, S.V., Fernandez, G., Fisher, S.E., Franke, B., Haatveit, Beathe, Hartman, C.A., Hoekstra, P.J., Håberg, Asta K., Jönsson, Erik G., Kolskår, Knut K., Le Hellard, Stephanie, Lund, Martina J., Lundervold, Astri J., Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C., Nordvik, Jan E., Nyberg, Lars, Oosterlaan, J., Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J. F., Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, A.N., Steen, Vidar M., Tønnesen, Siren, Ulrichsen, Kristine M., Zwiers, M.P., Andreassen, O.A., Westlye, L.T., Meer, D. van der, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E., Smeland, Olav B., Agartz, I., Bertolino, Alessandro, Bralten, J.B., Brandt, Christine L., Buitelaar, J.K., Djurovic, Srdjan, Donkelaar, M.M.J. van, Dørum, Erlend S., Espeseth, Thomas, Faraone, S.V., Fernandez, G., Fisher, S.E., Franke, B., Haatveit, Beathe, Hartman, C.A., Hoekstra, P.J., Håberg, Asta K., Jönsson, Erik G., Kolskår, Knut K., Le Hellard, Stephanie, Lund, Martina J., Lundervold, Astri J., Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C., Nordvik, Jan E., Nyberg, Lars, Oosterlaan, J., Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J. F., Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, A.N., Steen, Vidar M., Tønnesen, Siren, Ulrichsen, Kristine M., Zwiers, M.P., Andreassen, O.A., and Westlye, L.T.
Abstract: Contains fulltext : 199959.pdf (publisher's version ) (Open Access) Contains fulltext : 199959pos.pdf (postprint version ) (Open Access)
Published: 2020

14. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

Author: Meer, D. van der, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E., Smeland, Olav B., Agartz, I., Bertolino, Alessandro, Bralten, J.B., Brandt, Christine L., Buitelaar, J.K., Djurovic, Srdjan, Donkelaar, M.M.J. van, Dørum, Erlend S., Espeseth, Thomas, Faraone, S.V., Fernandez, G., Fisher, S.E., Franke, B., Haatveit, Beathe, Hartman, C.A., Hoekstra, P.J., Håberg, Asta K., Jönsson, Erik G., Kolskår, Knut K., Le Hellard, Stephanie, Lund, Martina J., Lundervold, Astri J., Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C., Nordvik, Jan E., Nyberg, Lars, Oosterlaan, J., Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J. F., Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, A.N., Steen, Vidar M., Tønnesen, Siren, Ulrichsen, Kristine M., Zwiers, M.P., Andreassen, O.A., Westlye, L.T., Meer, D. van der, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E., Smeland, Olav B., Agartz, I., Bertolino, Alessandro, Bralten, J.B., Brandt, Christine L., Buitelaar, J.K., Djurovic, Srdjan, Donkelaar, M.M.J. van, Dørum, Erlend S., Espeseth, Thomas, Faraone, S.V., Fernandez, G., Fisher, S.E., Franke, B., Haatveit, Beathe, Hartman, C.A., Hoekstra, P.J., Håberg, Asta K., Jönsson, Erik G., Kolskår, Knut K., Le Hellard, Stephanie, Lund, Martina J., Lundervold, Astri J., Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C., Nordvik, Jan E., Nyberg, Lars, Oosterlaan, J., Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J. F., Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, A.N., Steen, Vidar M., Tønnesen, Siren, Ulrichsen, Kristine M., Zwiers, M.P., Andreassen, O.A., and Westlye, L.T.
Abstract: Contains fulltext : 199959.pdf (publisher's version ) (Open Access) Contains fulltext : 199959pos.pdf (postprint version ) (Open Access)
Published: 2020

15. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, Kaufmann, Tobias, Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, and Kaufmann, Tobias
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
Published: 2020
Full Text: View/download PDF

16. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, Kaufmann, Tobias, Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, and Kaufmann, Tobias
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
Published: 2020
Full Text: View/download PDF

17. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, Kaufmann, Tobias, Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, and Kaufmann, Tobias
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
Published: 2020
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18. Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma : Results from two independent African cohorts

Author: Conrad, Daniela, Wilker, Sarah, Schneider, Anna, Karabatsiakis, Alexander, Pfeiffer, Anett, Kolassa, Stephan, Freytag, Virginie, Vukojevic, Vanja, Vogler, Christian, Milnik, Annette, Papassotiropoulos, Andreas, J.-F. de Quervain, Dominique, Elbert, Thomas, Kolassa, Iris Tatjana, Conrad, Daniela, Wilker, Sarah, Schneider, Anna, Karabatsiakis, Alexander, Pfeiffer, Anett, Kolassa, Stephan, Freytag, Virginie, Vukojevic, Vanja, Vogler, Christian, Milnik, Annette, Papassotiropoulos, Andreas, J.-F. de Quervain, Dominique, Elbert, Thomas, and Kolassa, Iris Tatjana
Abstract: The risk of developing posttraumatic stress disorder (PTSD) increases with the number of traumatic event types experienced (trauma load) in interaction with other psychobiological risk factors. The NOTCH (neurogenic locus notch homolog proteins) signaling pathway, consisting of four different trans-membrane receptor proteins (NOTCH1–4), constitutes an evolutionarily well-conserved intercellular communication pathway (involved, e.g., in cell–cell interaction, inflammatory signaling, and learning processes). Its association with fear memory consolidation makes it an interesting candidate for PTSD research. We tested for significant associations of common genetic variants of NOTCH1–4 (investigated by microarray) and genomic methylation of saliva-derived DNA with lifetime PTSD risk in independent cohorts from Northern Uganda (N1 = 924) and Rwanda (N2 = 371), and investigated whether NOTCH-related gene sets were enriched for associations with lifetime PTSD risk. We found associations of lifetime PTSD risk with single nucleotide polymorphism (SNP) rs2074621 (NOTCH3) (puncorrected= 0.04) in both cohorts, and with methylation of CpG site cg17519949 (NOTCH3) (puncorrected= 0.05) in Rwandans. Yet, none of the (epi-)genetic associations survived multiple testing correction. Gene set enrichment analyses revealed enrichment for associations of two NOTCH pathways with lifetime PTSD risk in Ugandans: NOTCH binding (pcorrected= 0.003) and NOTCH receptor processing (pcorrected= 0.01). The environmental factor trauma load was significant in all analyses (all p < 0.001). Our integrated methodological approach suggests NOTCH as a possible mediator of PTSD risk after trauma. The results require replication, and the precise underlying pathophysiological mechanisms should be illuminated in future studies.
Published: 2020

19. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

Author: van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, Westlye, Lars T, van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, and Westlye, Lars T
Abstract: The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
Published: 2020
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20. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
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21. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, Kaufmann, Tobias, Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K, Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A, Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jonassen, Rune, Jönsson, Erik G, Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, Connell, Kevin S O', Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A, Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, and Kaufmann, Tobias
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
Published: 2020
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22. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
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23. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

Author: van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, Westlye, Lars T, van der Meer, Dennis, Rokicki, Jaroslav, Kaufmann, Tobias, Córdova-Palomera, Aldo, Moberget, Torgeir, Alnæs, Dag, Bettella, Francesco, Frei, Oleksandr, Doan, Nhat Trung, Sønderby, Ida E, Smeland, Olav B, Agartz, Ingrid, Bertolino, Alessandro, Bralten, Janita, Brandt, Christine L, Buitelaar, Jan K, Djurovic, Srdjan, van Donkelaar, Marjolein, Dørum, Erlend S, Espeseth, Thomas, Faraone, Stephen V, Fernández, Guillén, Fisher, Simon E, Franke, Barbara, Haatveit, Beathe, Hartman, Catharina A, Hoekstra, Pieter J, Håberg, Asta K, Jönsson, Erik G, Kolskår, Knut K, Le Hellard, Stephanie, Lund, Martina J, Lundervold, Astri J, Lundervold, Arvid, Melle, Ingrid, Monereo Sánchez, Jennifer, Norbom, Linn C, Nordvik, Jan E, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pergola, Giulio, de Quervain, Dominique J F, Richard, Geneviève, Sanders, Anne-Marthe, Selvaggi, Pierluigi, Shumskaya, Elena, Steen, Vidar M, Tønnesen, Siren, Ulrichsen, Kristine M, Zwiers, Marcel P, Andreassen, Ole A, and Westlye, Lars T
Abstract: The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
Published: 2020
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24. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder

Author: Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: 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
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25. Common brain disorders are associated with heritable patterns of apparent aging of the brain

Author: Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnaes, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K., Boen, Erlend, Borgwardt, Stefan, Brandt, Christine L., Buitelaar, Jan, Celius, Elisabeth G., Cervenka, Simon, Conzelmann, Annette, Cordova-Palomera, Aldo, Dale, Anders M., de Quervain, Dominique J. F., Carlo, PasqualeDi, Djurovic, Srdjan, Dorum, Erlend S., Eisenacher, Sarah, Elvsashagen, Torbjorn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Haberg, Asta K., Harbo, Hanne F., Hartman, Catharina A., Heslenfeld, Dirk, Hoekstra, Pieter J., Hogestol, Einar A., Jernigan, Terry L., Jonassen, Rune, Jonsson, Erik G., Kirsch, Peter, Ktoszewska, Iwona, Kolskar, Knut K., Landro, Nils Inge, Hellard, StephanieLe, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J., Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B., Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Genevieve, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbaek, Geir, Shadrin, Alexey A., Smeland, Olav B., Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Ulrichsen, Kristine M., Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Farde, Lars, Flyckts, Lena, Engberg, Goran, Erhardt, Sophie, Fatouros-Bergmann, Helena, Schwieler, Lilly, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnaes, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K., Boen, Erlend, Borgwardt, Stefan, Brandt, Christine L., Buitelaar, Jan, Celius, Elisabeth G., Cervenka, Simon, Conzelmann, Annette, Cordova-Palomera, Aldo, Dale, Anders M., de Quervain, Dominique J. F., Carlo, PasqualeDi, Djurovic, Srdjan, Dorum, Erlend S., Eisenacher, Sarah, Elvsashagen, Torbjorn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Haberg, Asta K., Harbo, Hanne F., Hartman, Catharina A., Heslenfeld, Dirk, Hoekstra, Pieter J., Hogestol, Einar A., Jernigan, Terry L., Jonassen, Rune, Jonsson, Erik G., Kirsch, Peter, Ktoszewska, Iwona, Kolskar, Knut K., Landro, Nils Inge, Hellard, StephanieLe, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J., Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B., Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Genevieve, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbaek, Geir, Shadrin, Alexey A., Smeland, Olav B., Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Ulrichsen, Kristine M., Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Farde, Lars, Flyckts, Lena, Engberg, Goran, Erhardt, Sophie, Fatouros-Bergmann, Helena, Schwieler, Lilly, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, and Orhan, Funda
Abstract: Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
Published: 2019
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26. Common brain disorders are associated with heritable patterns of apparent aging of the brain.

Author: Kaufmann, Tobias, Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K, Bøen, Erlend, Borgwardt, Stefan, Brandt, Christine L, Buitelaar, Jan, Celius, Elisabeth G, Cervenka, Simon, Conzelmann, Annette, Córdova-Palomera, Aldo, Dale, Anders M, de Quervain, Dominique JF, Di Carlo, Pasquale, Djurovic, Srdjan, Dørum, Erlend S, Eisenacher, Sarah, Elvsåshagen, Torbjørn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Håberg, Asta K, Harbo, Hanne F, Hartman, Catharina A, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jernigan, Terry L, Jonassen, Rune, Jönsson, Erik G, Karolinska Schizophrenia Project (KaSP), Kirsch, Peter, Kłoszewska, Iwona, Kolskår, Knut K, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B, Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Geneviève, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbæk, Geir, Shadrin, Alexey A, Smeland, Olav B, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Ulrichsen, Kristine M, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, Kaufmann, Tobias, Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K, Bøen, Erlend, Borgwardt, Stefan, Brandt, Christine L, Buitelaar, Jan, Celius, Elisabeth G, Cervenka, Simon, Conzelmann, Annette, Córdova-Palomera, Aldo, Dale, Anders M, de Quervain, Dominique JF, Di Carlo, Pasquale, Djurovic, Srdjan, Dørum, Erlend S, Eisenacher, Sarah, Elvsåshagen, Torbjørn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Håberg, Asta K, Harbo, Hanne F, Hartman, Catharina A, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jernigan, Terry L, Jonassen, Rune, Jönsson, Erik G, Karolinska Schizophrenia Project (KaSP), Kirsch, Peter, Kłoszewska, Iwona, Kolskår, Knut K, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B, Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Geneviève, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbæk, Geir, Shadrin, Alexey A, Smeland, Olav B, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Ulrichsen, Kristine M, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, and Westlye, Lars T
Abstract: Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
Published: 2019

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

Author: Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: 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
Full Text: View/download PDF

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

Author: Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: 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
Full Text: View/download PDF

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

Author: Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: 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
Full Text: View/download PDF

30. Common brain disorders are associated with heritable patterns of apparent aging of the brain

Author: Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnaes, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K., Boen, Erlend, Borgwardt, Stefan, Brandt, Christine L., Buitelaar, Jan, Celius, Elisabeth G., Cervenka, Simon, Conzelmann, Annette, Cordova-Palomera, Aldo, Dale, Anders M., de Quervain, Dominique J. F., Carlo, PasqualeDi, Djurovic, Srdjan, Dorum, Erlend S., Eisenacher, Sarah, Elvsashagen, Torbjorn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Haberg, Asta K., Harbo, Hanne F., Hartman, Catharina A., Heslenfeld, Dirk, Hoekstra, Pieter J., Hogestol, Einar A., Jernigan, Terry L., Jonassen, Rune, Jonsson, Erik G., Kirsch, Peter, Ktoszewska, Iwona, Kolskar, Knut K., Landro, Nils Inge, Hellard, StephanieLe, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J., Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B., Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Genevieve, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbaek, Geir, Shadrin, Alexey A., Smeland, Olav B., Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Ulrichsen, Kristine M., Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Farde, Lars, Flyckts, Lena, Engberg, Goran, Erhardt, Sophie, Fatouros-Bergmann, Helena, Schwieler, Lilly, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnaes, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K., Boen, Erlend, Borgwardt, Stefan, Brandt, Christine L., Buitelaar, Jan, Celius, Elisabeth G., Cervenka, Simon, Conzelmann, Annette, Cordova-Palomera, Aldo, Dale, Anders M., de Quervain, Dominique J. F., Carlo, PasqualeDi, Djurovic, Srdjan, Dorum, Erlend S., Eisenacher, Sarah, Elvsashagen, Torbjorn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Haberg, Asta K., Harbo, Hanne F., Hartman, Catharina A., Heslenfeld, Dirk, Hoekstra, Pieter J., Hogestol, Einar A., Jernigan, Terry L., Jonassen, Rune, Jonsson, Erik G., Kirsch, Peter, Ktoszewska, Iwona, Kolskar, Knut K., Landro, Nils Inge, Hellard, StephanieLe, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J., Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B., Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Genevieve, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbaek, Geir, Shadrin, Alexey A., Smeland, Olav B., Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Ulrichsen, Kristine M., Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Farde, Lars, Flyckts, Lena, Engberg, Goran, Erhardt, Sophie, Fatouros-Bergmann, Helena, Schwieler, Lilly, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, and Orhan, Funda
Abstract: Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
Published: 2019
Full Text: View/download PDF

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

Author: Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: 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
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32. Common brain disorders are associated with heritable patterns of apparent aging of the brain.

Author: Kaufmann, Tobias, Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K, Bøen, Erlend, Borgwardt, Stefan, Brandt, Christine L, Buitelaar, Jan, Celius, Elisabeth G, Cervenka, Simon, Conzelmann, Annette, Córdova-Palomera, Aldo, Dale, Anders M, de Quervain, Dominique JF, Di Carlo, Pasquale, Djurovic, Srdjan, Dørum, Erlend S, Eisenacher, Sarah, Elvsåshagen, Torbjørn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Håberg, Asta K, Harbo, Hanne F, Hartman, Catharina A, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jernigan, Terry L, Jonassen, Rune, Jönsson, Erik G, Karolinska Schizophrenia Project (KaSP), Kirsch, Peter, Kłoszewska, Iwona, Kolskår, Knut K, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B, Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Geneviève, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbæk, Geir, Shadrin, Alexey A, Smeland, Olav B, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Ulrichsen, Kristine M, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, Westlye, Lars T, Kaufmann, Tobias, Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M, Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K, Bøen, Erlend, Borgwardt, Stefan, Brandt, Christine L, Buitelaar, Jan, Celius, Elisabeth G, Cervenka, Simon, Conzelmann, Annette, Córdova-Palomera, Aldo, Dale, Anders M, de Quervain, Dominique JF, Di Carlo, Pasquale, Djurovic, Srdjan, Dørum, Erlend S, Eisenacher, Sarah, Elvsåshagen, Torbjørn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Håberg, Asta K, Harbo, Hanne F, Hartman, Catharina A, Heslenfeld, Dirk, Hoekstra, Pieter J, Høgestøl, Einar A, Jernigan, Terry L, Jonassen, Rune, Jönsson, Erik G, Karolinska Schizophrenia Project (KaSP), Kirsch, Peter, Kłoszewska, Iwona, Kolskår, Knut K, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J, Maglanoc, Luigi A, Malt, Ulrik F, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B, Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Geneviève, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbæk, Geir, Shadrin, Alexey A, Smeland, Olav B, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M, Tsolaki, Magda, Ulrichsen, Kristine M, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C, Zink, Mathias, Andreassen, Ole A, and Westlye, Lars T
Abstract: Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
Published: 2019

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

Author: Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: 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
Full Text: View/download PDF

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

Author: Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: 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
Full Text: View/download PDF

35. Brain Disorders are Associated With Increased Brain Age

Author: Kaufmann, Tobias, van der Meer, Dennis, Doan, N. Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnaes, Dag, Barch, Deanna, Bertolino, Alessandro, Boen, Erlend, Borgwardt, Stefan, Conzelmann, Annette, Di Carlo, Pasquale, Djurovic, Srdjan, Elvsashagen, Torbjorn, Espeseth, Thomas, Fatouros-Bergmann, Helena, Flyckt, Lena, Franke, Barbara, Haberg, Asta, Joensson, Erik G., Kirsch, Peter, Landro, Nils I., Le Hellard, Stephanie, Lesch, Klaus-Peter, Malt, Ulrik F., Melle, Ingrid, Meyer-Lindenberg, Andreas, Nordvik, Jan Egil, Nyberg, Lars, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Selbaek, Geir, Steen, Vidar M., Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, van der Meer, Dennis, Doan, N. Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnaes, Dag, Barch, Deanna, Bertolino, Alessandro, Boen, Erlend, Borgwardt, Stefan, Conzelmann, Annette, Di Carlo, Pasquale, Djurovic, Srdjan, Elvsashagen, Torbjorn, Espeseth, Thomas, Fatouros-Bergmann, Helena, Flyckt, Lena, Franke, Barbara, Haberg, Asta, Joensson, Erik G., Kirsch, Peter, Landro, Nils I., Le Hellard, Stephanie, Lesch, Klaus-Peter, Malt, Ulrik F., Melle, Ingrid, Meyer-Lindenberg, Andreas, Nordvik, Jan Egil, Nyberg, Lars, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Selbaek, Geir, Steen, Vidar M., Andreassen, Ole A., and Westlye, Lars T.
Abstract: Supplement: S, Meeting Abstract: F5
Published: 2018

36. Genetic Architecture of Hippocampal Subfield Volumes : Shared and Specific Influences

Author: van der Meer, Dennis, Kaufmann, Tobias, Cordova-Palomera, Aldo, Bettella, Francesco, Frei, Oleksandr, Doan, N. Trung, Alnaes, Dag, Moberget, Torgeir, Agartz, Ingrid, Bertolino, Alessandro, Brandt, Christine L., Buitelaar, Jan K., Djurovic, Srdjan, Dorum, Erlend D., Espeseth, Thomas, Faraone, Stephen V., Franke, Barbara, Haberg, Asta, Haatveit, Beathe C., Hartman, Catharina, Le Hellard, Stephanie, Heslenfeld, Dirk, Hoekstra, Pieter, Jonsson, Erik G., Kolskar, Knut, Lund, Martina J., Melle, Ingrid, Norbom, Linn B., Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, Papassotiropoulos, Andreas, Pergola, Giulio, Richard, Genevieve, Sanders, Anne-Marthe, Steen, Vidar M., Ulrichsen, Kristine M., Andreassen, Ole, Westlye, Lars T., van der Meer, Dennis, Kaufmann, Tobias, Cordova-Palomera, Aldo, Bettella, Francesco, Frei, Oleksandr, Doan, N. Trung, Alnaes, Dag, Moberget, Torgeir, Agartz, Ingrid, Bertolino, Alessandro, Brandt, Christine L., Buitelaar, Jan K., Djurovic, Srdjan, Dorum, Erlend D., Espeseth, Thomas, Faraone, Stephen V., Franke, Barbara, Haberg, Asta, Haatveit, Beathe C., Hartman, Catharina, Le Hellard, Stephanie, Heslenfeld, Dirk, Hoekstra, Pieter, Jonsson, Erik G., Kolskar, Knut, Lund, Martina J., Melle, Ingrid, Norbom, Linn B., Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, Papassotiropoulos, Andreas, Pergola, Giulio, Richard, Genevieve, Sanders, Anne-Marthe, Steen, Vidar M., Ulrichsen, Kristine M., Andreassen, Ole, and Westlye, Lars T.
Abstract: Supplement: S, Meeting Abstract: F50
Published: 2018

37. Genetic estimators of DNA methylation provide insights into the molecular basis of polygenic traits

Author: Freytag, Virginie, Vukojevic, Vanja, Wagner-Thelen, Holger, Milnik, Annette, Vogler, Christian, Leber, Markus, Weinhold, Leonie, Boehmer, Anne C., Riedel-Heller, Steffi, Maier, Wolfgang, de Quervain, Dominique J. -F., Ramirez, Alfredo, Papassotiropoulos, Andreas, Freytag, Virginie, Vukojevic, Vanja, Wagner-Thelen, Holger, Milnik, Annette, Vogler, Christian, Leber, Markus, Weinhold, Leonie, Boehmer, Anne C., Riedel-Heller, Steffi, Maier, Wolfgang, de Quervain, Dominique J. -F., Ramirez, Alfredo, and Papassotiropoulos, Andreas
Abstract: The large biological distance between genetic risk loci and their mechanistic consequences in the tissue of interest limits the ability to establish functionality of susceptibility variants for genetically complex traits. Such a biological gap may be reduced through the systematic study of molecular mediators of genomic action, such as epigenetic modification. Here, we report the identification of robust genetic estimators of whole-blood CpG methylation, which can serve as intermediate molecular traits amenable to association testing with other genetically complex traits. We describe the relationship between these estimators and gene expression, demonstrate their genome-wide applicability to association testing even in the absence of individual genotypic data, and show that these estimators powerfully identify methylation-related genomic loci associated with polygenic traits and common diseases, such as schizophrenia. The use of genetic estimators for blood DNA methylation, which are made publically available, can serve as a valuable tool for the identification of epigenetic underpinnings of complex traits.
Published: 2018

38. Genetic variation is associated with PTSD risk and aversive memory : Evidence from two trauma-Exposed African samples and one healthy European sample

Author: Wilker, Sarah, Schneider, Anna, Conrad, Daniela, Pfeiffer, Anett, Boeck, Christina, Lingenfelder, Birke, Freytag, Virginie, Vukojevic, Vanja, Vogler, Christian, Milnik, Annette, Papassotiropoulos, Andreas, J.-F. de Quervain, Dominique, Elbert, Thomas, Kolassa, Stephan, Kolassa, Iris Tatjana, Wilker, Sarah, Schneider, Anna, Conrad, Daniela, Pfeiffer, Anett, Boeck, Christina, Lingenfelder, Birke, Freytag, Virginie, Vukojevic, Vanja, Vogler, Christian, Milnik, Annette, Papassotiropoulos, Andreas, J.-F. de Quervain, Dominique, Elbert, Thomas, Kolassa, Stephan, and Kolassa, Iris Tatjana
Abstract: The probability to develop posttraumatic stress disorder (PTSD), characterized by vivid, intrusive emotional memories of the encountered traumatic events, depends - among other factors - on the number of previous traumatic experiences (traumatic load) and individual genetic vulnerability. So far, our knowledge regarding the biological underpinnings of PTSD is relatively sparse. Genome-wide association studies (GWAS) followed by independent replication might help to discover novel, so far unknown biological mechanisms associated with the development of traumatic memories. Here, a GWAS was conducted in N = 924 Northern Ugandan rebel war survivors and identified seven suggestively significant single nucleotide polymorphisms (SNPs; p ≤ 1 × 10−5) for lifetime PTSD risk. Of these seven SNPs, the association of rs3852144 on chromosome 5 was replicated in an independent sample of Rwandan genocide survivors (N = 370, p <.01). While PTSD risk increased with accumulating traumatic experiences, the vulnerability was reduced in carriers of the minor G-allele in an additive manner. Correspondingly, memory for aversive pictures decreased with higher number of the minor G-allele in a sample of N = 2698 healthy Swiss individuals. Finally, investigations on N = 90 PTSD patients treated with Narrative Exposure Therapy indicated an additive effect of genotype on PTSD symptom change from pre-treatment to four months after treatment, but not between pre-treatment and the 10-months follow-up. In conclusion, emotional memory formation seems to decline with increasing number of rs3852144 G-alleles, rendering individuals more resilient to PTSD development. However, the impact on therapy outcome remains preliminary and further research is needed to determine how this intronic marker may affect memory processes in detail.
Published: 2018

39. NGS-pipe: a flexible, easily extendable, and highly configurable framework for NGS analysis

Author: Singer, Jochen, Ruscheweyh, Hans-Joachim, Hofmann, Ariane L, Thurnherr, Thomas, Singer, Franziska, Toussaint, Nora C, Ng, Charlotte K Y, Piscuoglio, Salvatore, Beisel, Christian, Christofori, Gerhard, Dummer, Reinhard, Hall, Michael N, Krek, Wilhelm, Levesque, Mitchell P; https://orcid.org/0000-0001-5902-9420, Manz, Markus G, Moch, Holger, Papassotiropoulos, Andreas, Stekhoven, Daniel J, Wild, Peter, Wüst, Thomas, Rinn, Bernd, Beerenwinkel, Niko, Singer, Jochen, Ruscheweyh, Hans-Joachim, Hofmann, Ariane L, Thurnherr, Thomas, Singer, Franziska, Toussaint, Nora C, Ng, Charlotte K Y, Piscuoglio, Salvatore, Beisel, Christian, Christofori, Gerhard, Dummer, Reinhard, Hall, Michael N, Krek, Wilhelm, Levesque, Mitchell P; https://orcid.org/0000-0001-5902-9420, Manz, Markus G, Moch, Holger, Papassotiropoulos, Andreas, Stekhoven, Daniel J, Wild, Peter, Wüst, Thomas, Rinn, Bernd, and Beerenwinkel, Niko
Abstract: Motivation: Next-generation sequencing is now an established method in genomics, and massive amounts of sequencing data are being generated on a regular basis. Analysis of the sequencing data is typically performed by lab-specific in-house solutions, but the agreement of results from different facilities is often small. General standards for quality control, reproducibility, and documentation are missing. Results: We developed NGS-pipe, a flexible, transparent, and easy-to-use framework for the design of pipelines to analyze whole-exome, whole-genome, and transcriptome sequencing data. NGS-pipe facilitates the harmonization of genomic data analysis by supporting quality control, documentation, reproducibility, parallelization, and easy adaptation to other NGS experiments.
Published: 2018

40. Genetic estimators of DNA methylation provide insights into the molecular basis of polygenic traits

Author: Freytag, Virginie, Vukojevic, Vanja, Wagner-Thelen, Holger, Milnik, Annette, Vogler, Christian, Leber, Markus, Weinhold, Leonie, Boehmer, Anne C., Riedel-Heller, Steffi, Maier, Wolfgang, de Quervain, Dominique J. -F., Ramirez, Alfredo, Papassotiropoulos, Andreas, Freytag, Virginie, Vukojevic, Vanja, Wagner-Thelen, Holger, Milnik, Annette, Vogler, Christian, Leber, Markus, Weinhold, Leonie, Boehmer, Anne C., Riedel-Heller, Steffi, Maier, Wolfgang, de Quervain, Dominique J. -F., Ramirez, Alfredo, and Papassotiropoulos, Andreas
Abstract: The large biological distance between genetic risk loci and their mechanistic consequences in the tissue of interest limits the ability to establish functionality of susceptibility variants for genetically complex traits. Such a biological gap may be reduced through the systematic study of molecular mediators of genomic action, such as epigenetic modification. Here, we report the identification of robust genetic estimators of whole-blood CpG methylation, which can serve as intermediate molecular traits amenable to association testing with other genetically complex traits. We describe the relationship between these estimators and gene expression, demonstrate their genome-wide applicability to association testing even in the absence of individual genotypic data, and show that these estimators powerfully identify methylation-related genomic loci associated with polygenic traits and common diseases, such as schizophrenia. The use of genetic estimators for blood DNA methylation, which are made publically available, can serve as a valuable tool for the identification of epigenetic underpinnings of complex traits.
Published: 2018

41. Association study of cholesterol-related genes in Alzheimer's disease

Author: Wollmer, M., Sleegers, Kristel, Ingelsson, Martin, Zekanowski, Cezary, Brouwers, Nathalie, Maruszak, Aleksandra, Brunner, Fabienne, Huynh, Kim-Dung, Kilander, Lena, Brundin, Rose-Marie, Hedlund, Marie, Giedraitis, Vilmantas, Glaser, Anna, Engelborghs, Sebastiaan, De Deyn, Peter, Kapaki, Elisabeth, Tsolaki, Magdalini, Daniilidou, Makrina, Molyva, Dimitra, Paraskevas, George, Thal, Dietmar, Barcikowska, Maria, Kuznicki, Jacek, Lannfelt, Lars, Van Broeckhoven, Christine, Nitsch, Roger, Hock, Christoph, Papassotiropoulos, Andreas, Wollmer, M., Sleegers, Kristel, Ingelsson, Martin, Zekanowski, Cezary, Brouwers, Nathalie, Maruszak, Aleksandra, Brunner, Fabienne, Huynh, Kim-Dung, Kilander, Lena, Brundin, Rose-Marie, Hedlund, Marie, Giedraitis, Vilmantas, Glaser, Anna, Engelborghs, Sebastiaan, De Deyn, Peter, Kapaki, Elisabeth, Tsolaki, Magdalini, Daniilidou, Makrina, Molyva, Dimitra, Paraskevas, George, Thal, Dietmar, Barcikowska, Maria, Kuznicki, Jacek, Lannfelt, Lars, Van Broeckhoven, Christine, Nitsch, Roger, Hock, Christoph, and Papassotiropoulos, Andreas
Abstract: Alzheimer's disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P ≤ 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples
Published: 2018

42. A peripheral epigenetic signature of immune system genes is linked to neocortical thickness and memory

Author: Freytag, Virginie, Carrillo-Roa, Tania, Milnik, Annette, Mann, Philipp G. Sa, Vukojevic, Vanja, Coynel, David, Demougin, Philippe, Egli, Tobias, Gschwind, Leo, Jessen, Frank, Loos, Eva, Maier, Wolfgang, Riedel-Heller, Steffi G., Scherer, Martin, Vogler, Christian, Wagner, Michael, Binder, Elisabeth B., de Quervain, Dominique J. -F., Papassotiropoulos, Andreas, Freytag, Virginie, Carrillo-Roa, Tania, Milnik, Annette, Mann, Philipp G. Sa, Vukojevic, Vanja, Coynel, David, Demougin, Philippe, Egli, Tobias, Gschwind, Leo, Jessen, Frank, Loos, Eva, Maier, Wolfgang, Riedel-Heller, Steffi G., Scherer, Martin, Vogler, Christian, Wagner, Michael, Binder, Elisabeth B., de Quervain, Dominique J. -F., and Papassotiropoulos, Andreas
Abstract: Increasing age is tightly linked to decreased thickness of the human neocortex. The biological mechanisms that mediate this effect are hitherto unknown. The DNA methylome, as part of the epigenome, contributes significantly to age-related phenotypic changes. Here, we identify an epigenetic signature that is associated with cortical thickness (P = 3.86 x 10(-8)) and memory performance in 533 healthy young adults. The epigenetic effect on cortical thickness was replicated in a sample comprising 596 participants with major depressive disorder and healthy controls. The epigenetic signature mediates partially the effect of age on cortical thickness (P < 0.001). A multilocus genetic score reflecting genetic variability of this signature is associated with memory performance (P = 0.0003) in 3,346 young and elderly healthy adults. The genomic location of the contributing methylation sites points to the involvement of specific immune system genes. The decomposition of blood methylome-wide patterns bears considerable potential for the study of brain-related traits.
Published: 2017

43. A peripheral epigenetic signature of immune system genes is linked to neocortical thickness and memory

Author: Freytag, Virginie, Carrillo-Roa, Tania, Milnik, Annette, Mann, Philipp G. Sa, Vukojevic, Vanja, Coynel, David, Demougin, Philippe, Egli, Tobias, Gschwind, Leo, Jessen, Frank, Loos, Eva, Maier, Wolfgang, Riedel-Heller, Steffi G., Scherer, Martin, Vogler, Christian, Wagner, Michael, Binder, Elisabeth B., de Quervain, Dominique J. -F., Papassotiropoulos, Andreas, Freytag, Virginie, Carrillo-Roa, Tania, Milnik, Annette, Mann, Philipp G. Sa, Vukojevic, Vanja, Coynel, David, Demougin, Philippe, Egli, Tobias, Gschwind, Leo, Jessen, Frank, Loos, Eva, Maier, Wolfgang, Riedel-Heller, Steffi G., Scherer, Martin, Vogler, Christian, Wagner, Michael, Binder, Elisabeth B., de Quervain, Dominique J. -F., and Papassotiropoulos, Andreas
Abstract: Increasing age is tightly linked to decreased thickness of the human neocortex. The biological mechanisms that mediate this effect are hitherto unknown. The DNA methylome, as part of the epigenome, contributes significantly to age-related phenotypic changes. Here, we identify an epigenetic signature that is associated with cortical thickness (P = 3.86 x 10(-8)) and memory performance in 533 healthy young adults. The epigenetic effect on cortical thickness was replicated in a sample comprising 596 participants with major depressive disorder and healthy controls. The epigenetic signature mediates partially the effect of age on cortical thickness (P < 0.001). A multilocus genetic score reflecting genetic variability of this signature is associated with memory performance (P = 0.0003) in 3,346 young and elderly healthy adults. The genomic location of the contributing methylation sites points to the involvement of specific immune system genes. The decomposition of blood methylome-wide patterns bears considerable potential for the study of brain-related traits.
Published: 2017

44. Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance

Author: Huentelman, Matthew J., Papassotiropoulos, Andreas, Craig, David W., Hoerndli, Frederic J., Pearson, John V., Huynh, Kim-Dung, Corneveaux, Jason, Hänggi, Jürgen, Mondadori, Christian R.A., Buchmann, Andreas, Reiman, Eric M., Henke, Katharina, de Quervain, Dominique J.-F, Stephan, Dietrich A., Huentelman, Matthew J., Papassotiropoulos, Andreas, Craig, David W., Hoerndli, Frederic J., Pearson, John V., Huynh, Kim-Dung, Corneveaux, Jason, Hänggi, Jürgen, Mondadori, Christian R.A., Buchmann, Andreas, Reiman, Eric M., Henke, Katharina, de Quervain, Dominique J.-F, and Stephan, Dietrich A.
Abstract: Little is known about the genes and proteins involved in the process of human memory. To identify genetic factors related to human episodic memory performance, we conducted an ultra-high-density genome-wide screen at > 500000 single nucleotide polymorphisms (SNPs) in a sample of normal young adults stratified for performance on an episodic recall memory test. Analysis of this data identified SNPs within the calmodulin-binding transcription activator 1 (CAMTA1) gene that were significantly associated with memory performance. A follow up study, focused on the CAMTA1 locus in an independent cohort consisting of cognitively normal young adults, singled out SNP rs4908449 with a P-value of 0.0002 as the most significant associated SNP in the region. These validated genetic findings were further supported by the identification of CAMTA1 transcript enrichment in memory-related human brain regions and through a functional magnetic resonance imaging experiment on individuals matched for memory performance that identified CAMTA1 allele-specific upregulation of medial temporal lobe brain activity in those individuals harboring the ‘at-risk' allele for poorer memory performance. The CAMTA1 locus encodes a purported transcription factor that interfaces with the calcium-calmodulin system of the cell to alter gene expression patterns. Our validated genomic and functional biological findings described herein suggest a role for CAMTA1 in human episodic memory
Published: 2017

45. The prion gene is associated with human long-term memory

Author: Papassotiropoulos, Andreas, Wollmer, M. Axel, Aguzzi, Adriano, Hock, Christoph, Nitsch, Roger M., de Quervain, Dominique J.-F, Papassotiropoulos, Andreas, Wollmer, M. Axel, Aguzzi, Adriano, Hock, Christoph, Nitsch, Roger M., and de Quervain, Dominique J.-F
Abstract: Human cognitive processes are highly variable across individuals and are influenced by both genetic and environmental factors. Although genetic variations affect short-term memory in humans, it is unknown whether genetic variability has also an impact on long-term memory. Because prion-like conformational changes may be involved in the induction of long-lasting synaptic plasticity, we examined the impact of single-nucleotide polymorphisms (SNPs) of the prion protein gene (PRNP) on long-term memory in healthy young humans. SNPs in the genomic region of PRNP were associated with better long-term memory performance in two independent populations with different educational background. Among the examined PRNP SNPs, the common Met129Val polymorphism yielded the highest effect size. Twenty-four hours after a word list-learning task, carriers of either the 129MM or the 129MV genotype recalled 17% more information than 129VV carriers, but short-term memory was unaffected. These results suggest a role for the prion protein in the formation of long-term memory in humans
Published: 2017

46. Associations among child abuse, mental health, and epigenetic modifications in the proopiomelanocortin gene (POMC): A study with children in Tanzania

Author: Hecker, Tobias, Radtke, Karl M, Hermenau, Katharin, Papassotiropoulos, Andreas, Elbert, Thomas, Hecker, Tobias, Radtke, Karl M, Hermenau, Katharin, Papassotiropoulos, Andreas, and Elbert, Thomas
Published: 2016

47. Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Author: Luksys, Gediminas, Fastenrath, Matthias, Coynel, David, Freytag, Virginie, Gschwind, Leo, Heck, Angela, Jessen, Frank, Maier, Wolfgang, Milnik, Annette, Riedel-Heller, Steffi G., Scherer, Martin, Spalek, Klara, Vogler, Christian, Wagner, Michael, Wolfsgruber, Steffen, Papassotiropoulos, Andreas, de Quervain, Dominique J. -F., Luksys, Gediminas, Fastenrath, Matthias, Coynel, David, Freytag, Virginie, Gschwind, Leo, Heck, Angela, Jessen, Frank, Maier, Wolfgang, Milnik, Annette, Riedel-Heller, Steffi G., Scherer, Martin, Spalek, Klara, Vogler, Christian, Wagner, Michael, Wolfsgruber, Steffen, Papassotiropoulos, Andreas, and de Quervain, Dominique J. -F.
Abstract: Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuro-modulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.
Published: 2015

48. Genetic Analysis of Association Between Calcium Signaling and Hippocampal Activation, Memory Performance in the Young and Old, and Risk for Sporadic Alzheimer Disease

Author: Heck, Angela, Fastenrath, Matthias, Coynel, David, Auschra, Bianca, Bickel, Horst, Freytag, Virginie, Gschwind, Leo, Hartmann, Francina, Jessen, Frank, Kaduszkiewicz, Hanna, Maier, Wolfgang, Milnik, Annette, Pentzek, Michael, Riedel-Heller, Steffi G., Spalek, Klara, Vogler, Christian, Wagner, Michael, Weyerer, Siegfried, Wolfsgruber, Steffen, de Quervain, Dominique J. -F., Papassotiropoulos, Andreas, Heck, Angela, Fastenrath, Matthias, Coynel, David, Auschra, Bianca, Bickel, Horst, Freytag, Virginie, Gschwind, Leo, Hartmann, Francina, Jessen, Frank, Kaduszkiewicz, Hanna, Maier, Wolfgang, Milnik, Annette, Pentzek, Michael, Riedel-Heller, Steffi G., Spalek, Klara, Vogler, Christian, Wagner, Michael, Weyerer, Siegfried, Wolfsgruber, Steffen, de Quervain, Dominique J. -F., and Papassotiropoulos, Andreas
Abstract: IMPORTANCE Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus; declines as a result of increasing age; and is markedly disturbed in Alzheimer disease (AD), an age-associated neurodegenerative disorder that primarily affects the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology. OBJECTIVE To determine whether biologically defined groups of genes are enriched in episodic memory performance across age, memory encoding-related brain activity, and AD. DESIGN, SETTING, AND PARTICIPANTS In this multicenter collaborative study, which began in August 2008 and is ongoing, gene set enrichment analysis was done by using primary and meta-analysis data from 57 968 participants. The Swiss cohorts consisted of 3043 healthy young adults assessed for episodic memory performance. In a subgroup (n = 1119) of one of these cohorts, functional magnetic resonance imaging was used to identify gene set-dependent differences in brain activity related to episodic memory. The German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort consisted of 763 elderly participants without dementia who were assessed for episodic memory performance. The International Genomics of Alzheimer's Project case-control sample consisted of 54 162 participants (17 008 patients with sporadic AD and 37 154 control participants). Analyses were conducted between January 2014 and June 2015. Gene set enrichment analysis in all samples was done using genome-wide single-nucleotide polymorphism data. MAIN OUTCOMES AND MEASURES Episodic memory performance in the Swiss cohort and German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort was quantified by picture and verbal delayed free recall tasks. In the functional magnetic resonance imaging experiment, activation of the hippocampus during encoding of pict
Published: 2015

49. Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Author: Luksys, Gediminas, Fastenrath, Matthias, Coynel, David, Freytag, Virginie, Gschwind, Leo, Heck, Angela, Jessen, Frank, Maier, Wolfgang, Milnik, Annette, Riedel-Heller, Steffi G., Scherer, Martin, Spalek, Klara, Vogler, Christian, Wagner, Michael, Wolfsgruber, Steffen, Papassotiropoulos, Andreas, de Quervain, Dominique J. -F., Luksys, Gediminas, Fastenrath, Matthias, Coynel, David, Freytag, Virginie, Gschwind, Leo, Heck, Angela, Jessen, Frank, Maier, Wolfgang, Milnik, Annette, Riedel-Heller, Steffi G., Scherer, Martin, Spalek, Klara, Vogler, Christian, Wagner, Michael, Wolfsgruber, Steffen, Papassotiropoulos, Andreas, and de Quervain, Dominique J. -F.
Abstract: Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuro-modulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.
Published: 2015

50. Genetic Analysis of Association Between Calcium Signaling and Hippocampal Activation, Memory Performance in the Young and Old, and Risk for Sporadic Alzheimer Disease

Author: Heck, Angela, Fastenrath, Matthias, Coynel, David, Auschra, Bianca, Bickel, Horst, Freytag, Virginie, Gschwind, Leo, Hartmann, Francina, Jessen, Frank, Kaduszkiewicz, Hanna, Maier, Wolfgang, Milnik, Annette, Pentzek, Michael, Riedel-Heller, Steffi G., Spalek, Klara, Vogler, Christian, Wagner, Michael, Weyerer, Siegfried, Wolfsgruber, Steffen, de Quervain, Dominique J. -F., Papassotiropoulos, Andreas, Heck, Angela, Fastenrath, Matthias, Coynel, David, Auschra, Bianca, Bickel, Horst, Freytag, Virginie, Gschwind, Leo, Hartmann, Francina, Jessen, Frank, Kaduszkiewicz, Hanna, Maier, Wolfgang, Milnik, Annette, Pentzek, Michael, Riedel-Heller, Steffi G., Spalek, Klara, Vogler, Christian, Wagner, Michael, Weyerer, Siegfried, Wolfsgruber, Steffen, de Quervain, Dominique J. -F., and Papassotiropoulos, Andreas
Abstract: IMPORTANCE Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus; declines as a result of increasing age; and is markedly disturbed in Alzheimer disease (AD), an age-associated neurodegenerative disorder that primarily affects the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology. OBJECTIVE To determine whether biologically defined groups of genes are enriched in episodic memory performance across age, memory encoding-related brain activity, and AD. DESIGN, SETTING, AND PARTICIPANTS In this multicenter collaborative study, which began in August 2008 and is ongoing, gene set enrichment analysis was done by using primary and meta-analysis data from 57 968 participants. The Swiss cohorts consisted of 3043 healthy young adults assessed for episodic memory performance. In a subgroup (n = 1119) of one of these cohorts, functional magnetic resonance imaging was used to identify gene set-dependent differences in brain activity related to episodic memory. The German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort consisted of 763 elderly participants without dementia who were assessed for episodic memory performance. The International Genomics of Alzheimer's Project case-control sample consisted of 54 162 participants (17 008 patients with sporadic AD and 37 154 control participants). Analyses were conducted between January 2014 and June 2015. Gene set enrichment analysis in all samples was done using genome-wide single-nucleotide polymorphism data. MAIN OUTCOMES AND MEASURES Episodic memory performance in the Swiss cohort and German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort was quantified by picture and verbal delayed free recall tasks. In the functional magnetic resonance imaging experiment, activation of the hippocampus during encoding of pict
Published: 2015

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