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Item Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years(Wiley, 2022-01) Frangou, Sophia; Modabbernia, Amirhossein; Williams, Steven C.R.; Papachristou, Efstathios; Doucet, Gaelle E.; Agartz, Ingrid; Aghajani, Moji; Akudjedu, Theophilus N.; Albajes-Eizagirre, Anton; Alnæs, Dag; Alpert, Kathryn I.; Andersson, Micael; Andreasen, Nancy C.; Andreassen, Ole A.; Asherson, Philip; Banaschewski, Tobias; Bargallo, Nuria; Baumeister, Sarah; Baur-Streubel, Ramona; Bertolino, Alessandro; Bonvino, Aurora; Boomsma, Dorret I.; Borgwardt, Stefan; Bourque, Josiane; Brandeis, Daniel; Breier, Alan; Brodaty, Henry; Brouwer, Rachel M.; Buitelaar, Jan K.; Busatto, Geraldo F.; Buckner, Randy L.; Calhoun, Vincent; Canales-Rodríguez, Erick J.; Cannon, Dara M.; Caseras, Xavier; Castellanos, Francisco X.; Cervenka, Simon; Chaim-Avancini, Tiffany M.; Ching, Christopher R.K.; Chubar, Victoria; Clark, Vincent P.; Conrod, Patricia; Conzelmann, Annette; Crespo-Facorro, Benedicto; Crivello, Fabrice; Crone, Eveline A.; Dale, Anders M.; Dannlowski, Udo; Davey, Christopher; de Geus, Eco J.C.; de Haan, Lieuwe; de Zubicaray, Greig I.; den Braber, Anouk; Dickie, Erin W.; Di Giorgio, Annabella; Doan, Nhat Trung; Dørum, Erlend S.; Ehrlich, Stefan; Erk, Susanne; Espeseth, Thomas; Fatouros-Bergman, Helena; Fisher, Simon E.; Fouche, Jean-Paul; Franke, Barbara; Frodl, Thomas; Fuentes-Claramonte, Paola; Glahn, David C.; Gotlib, Ian H.; Grabe, Hans-Jörgen; Grimm, Oliver; Groenewold, Nynke A.; Grotegerd, Dominik; Gruber, Oliver; Gruner, Patricia; Gur, Rachel E.; Gur, Ruben C.; Hahn, Tim; Harrison, Ben J.; Hartman, Catharine A.; Hatton, Sean N.; Heinz, Andreas; Heslenfeld, Dirk J.; Hibar, Derrek P.; Hickie, Ian B.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hohmann, Sarah; Holmes, Avram J.; Hoogman, Martine; Hosten, Norbert; Howells, Fleur M.; Hulshoff Pol, Hilleke E.; Huyser, Chaim; Jahanshad, Neda; James, Anthony; Jernigan, Terry L.; Jiang, Jiyang; Jönsson, Erik G.; Joska, John A.; Kahn, Rene; Kalnin, Andrew; Kanai, Ryota; Klein, Marieke; Klyushnik, Tatyana P.; Koenders, Laura; Koops, Sanne; Krämer, Bernd; Kuntsi, Jonna; Lagopoulos, Jim; Lázaro, Luisa; Lebedeva, Irina; Lee, Won Hee; Lesch, Klaus-Peter; Lochner, Christine; Machielsen, Marise W.J.; Maingault, Sophie; Martin, Nicholas G.; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Mazoyer, Bernard; McDonald, Colm; McDonald, Brenna C.; McIntosh, Andrew M.; McMahon, Katie L.; McPhilemy, Genevieve; Meinert, Susanne; Menchón, José M.; Medland, Sarah E.; Meyer-Lindenberg, Andreas; Naaijen, Jilly; Najt, Pablo; Nakao, Tomohiro; Nordvik, Jan E.; Nyberg, Lars; Oosterlaan, Jaap; Ortiz-García de la Foz, Víctor; Paloyelis, Yannis; Pauli, Paul; Pergola, Giulio; Pomarol-Clotet, Edith; Portella, Maria J.; Potkin, Steven G.; Radua, Joaquim; Reif, Andreas; Rinker, Daniel A.; Roffman, Joshua L.; Rosa, Pedro G.P.; Sacchet, Matthew D.; Sachdev, Perminder S.; Salvador, Raymond; Sánchez-Juan, Pascual; Sarró, Salvador; Satterthwaite, Theodore D.; Saykin, Andrew J.; Serpa, Mauricio H.; Schmaal, Lianne; Schnell, Knut; Schumann, Gunter; Sim, Kang; Smoller, Jordan W.; Sommer, Iris; Soriano-Mas, Carles; Stein, Dan J.; Strike, Lachlan T.; Swagerman, Suzanne C.; Tamnes, Christian K.; Temmingh, Henk S.; Thomopoulos, Sophia I.; Tomyshev, Alexander S.; Tordesillas-Gutiérrez, Diana; Trollor, Julian N.; Turner, Jessica A.; Uhlmann, Anne; van den Heuvel, Odile A.; van den Meer, Dennis; van der Wee, Nic J.A.; van Haren, Neeltje E.M.; van't Ent, Dennis; van Erp, Theo G.M.; Veer, Ilya M.; Veltman, Dick J.; Voineskos, Aristotle; Völzke, Henry; Walter, Henrik; Walton, Esther; Wang, Lei; Wang, Yang; Wassink, Thomas H.; Weber, Bernd; Wen, Wei; West, John D.; Westlye, Lars T.; Whalley, Heather; Wierenga, Lara M.; Wittfeld, Katharina; Wolf, Daniel H.; Worker, Amanda; Wright, Margaret J.; Yang, Kun; Yoncheva, Yulyia; Zanetti, Marcus V.; Ziegler, Georg C.; Karolinska Schizophrenia Project (KaSP); Thompson, Paul M.; Dima, Danai; Radiology and Imaging Sciences, School of MedicineDelineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.Item Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci(medRxiv, 2024-03-13) Strom, Nora I.; Gerring, Zachary F.; Galimberti, Marco; Yu, Dongmei; Halvorsen, Matthew W.; Abdellaoui, Abdel; Rodriguez-Fontenla, Cristina; Sealock, Julia M.; Bigdeli, Tim; Coleman, Jonathan R.; Mahjani, Behrang; Thorp, Jackson G.; Bey, Katharina; Burton, Christie L.; Luykx, Jurjen J.; Zai, Gwyneth; Alemany, Silvia; Andre, Christine; Askland, Kathleen D.; Banaj, Nerisa; Barlassina, Cristina; Becker Nissen, Judith; Bienvenu, O. Joseph; Black, Donald; Bloch, Michael H.; Boberg, Julia; Børte, Sigrid; Bosch, Rosa; Breen, Michael; Brennan, Brian P.; Brentani, Helena; Buxbaum, Joseph D.; Bybjerg-Grauholm, Jonas; Byrne, Enda M.; Cabana-Dominguez, Judith; Camarena, Beatriz; Camarena, Adrian; Cappi, Carolina; Carracedo, Angel; Casas, Miguel; Cavallini, Maria Cristina; Ciullo, Valentina; Cook, Edwin H.; Crosby, Jesse; Cullen, Bernadette A.; De Schipper, Elles J.; Delorme, Richard; Djurovic, Srdjan; Elias, Jason A.; Estivill, Xavier; Falkenstein, Martha J.; Fundin, Bengt T.; Garner, Lauryn; German, Chris; Gironda, Christina; Goes, Fernando S.; Grados, Marco A.; Grove, Jakob; Guo, Wei; Haavik, Jan; Hagen, Kristen; Harrington, Kelly; Havdahl, Alexandra; Höffler, Kira D.; Hounie, Ana G.; Hucks, Donald; Hultman, Christina; Janecka, Magdalena; Jenike, Eric; Karlsson, Elinor K.; Kelley, Kara; Klawohn, Julia; Krasnow, Janice E.; Krebs, Kristi; Lange, Christoph; Lanzagorta, Nuria; Levey, Daniel; Lindblad-Toh, Kerstin; Macciardi, Fabio; Maher, Brion; Mathes, Brittany; McArthur, Evonne; McGregor, Nathaniel; McLaughlin, Nicole C.; Meier, Sandra; Miguel, Euripedes C.; Mulhern, Maureen; Nestadt, Paul S.; Nurmi, Erika L.; O'Connell, Kevin S.; Osiecki, Lisa; Ousdal, Olga Therese; Palviainen, Teemu; Pedersen, Nancy L.; Piras, Fabrizio; Piras, Federica; Potluri, Sriramya; Rabionet, Raquel; Ramirez, Alfredo; Rauch, Scott; Reichenberg, Abraham; Riddle, Mark A.; Ripke, Stephan; Rosário, Maria C.; Sampaio, Aline S.; Schiele, Miriam A.; Skogholt, Anne Heidi; Sloofman, Laura G.; Smit, Jan; Soler, Artigas María; Thomas, Laurent F.; Tifft, Eric; Vallada, Homero; van Kirk, Nathanial; Veenstra-VanderWeele, Jeremy; Vulink, Nienke N.; Walker, Christopher P.; Wang, Ying; Wendland, Jens R.; Winsvold, Bendik S.; Yao, Yin; Zhou, Hang; 23andMe Research Team; VA Million Veteran Program; Estonian Biobank; CoGa research team; iPSYCH; HUNT research team; NORDiC research team; Agrawal, Arpana; Alonso, Pino; Berberich, Götz; Bucholz, Kathleen K.; Bulik, Cynthia M.; Cath, Danielle; Denys, Damiaan; Eapen, Valsamma; Edenberg, Howard; Falkai, Peter; Fernandez, Thomas V.; Fyer, Abby J.; Gaziano, J. M.; Geller, Dan A.; Grabe, Hans J.; Greenberg, Benjamin D.; Hanna, Gregory L.; Hickie, Ian B.; Hougaard, David M.; Kathmann, Norbert; Kennedy, James; Lai, Dongbing; Landén, Mikael; Le Hellard, Stéphanie; Leboyer, Marion; Lochner, Christine; McCracken, James T.; Medland, Sarah E.; Mortensen, Preben B.; Neale, Benjamin M.; Nicolini, Humberto; Nordentoft, Merete; Pato, Michele; Pato, Carlos; Pauls, David L.; Piacentini, John; Pittenger, Christopher; Posthuma, Danielle; Ramos-Quiroga, Josep Antoni; Rasmussen, Steven A.; Richter, Margaret A.; Rosenberg, David R.; Ruhrmann, Stephan; Samuels, Jack F.; Sandin, Sven; Sandor, Paul; Spalletta, Gianfranco; Stein, Dan J.; Stewart, S. Evelyn; Storch, Eric A.; Stranger, Barbara E.; Turiel, Maurizio; Werge, Thomas; Andreassen, Ole A.; Børglum, Anders D.; Walitza, Susanne; Hveem, Kristian; Hansen, Bjarne K.; Rück, Christian P.; Martin, Nicholas G.; Milani, Lili; Mors, Ole; Reichborn-Kjennerud, Ted; Ribasés, Marta; Kvale, Gerd; Mataix-Cols, David; Domschke, Katharina; Grünblatt, Edna; Wagner, Michael; Zwart, John-Anker; Breen, Gerome; Nestadt, Gerald; Kaprio, Jaakko; Arnold, Paul D.; Grice, Dorothy E.; Knowles, James A.; Ask, Helga; Verweij, Karin J.; Davis, Lea K.; Smit, Dirk J.; Crowley, James J.; Scharf, Jeremiah M.; Stein, Murray B.; Gelernter, Joel; Mathews, Carol A.; Derks, Eske M.; Mattheisen, Manuel; Biochemistry and Molecular Biology, School of MedicineObsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.Item Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years(Wiley, 2022) Dima, Danai; Modabbernia, Amirhossein; Papachristou, Efstathios; Doucet, Gaelle E.; Agartz, Ingrid; Aghajani, Moji; Akudjedu, Theophilus N.; Albajes-Eizagirre, Anton; Alnæs, Dag; Alpert, Kathryn I.; Andersson, Micael; Andreasen, Nancy C.; Andreassen, Ole A.; Asherson, Philip; Banaschewski, Tobias; Bargallo, Nuria; Baumeister, Sarah; Baur-Streubel, Ramona; Bertolino, Alessandro; Bonvino, Aurora; Boomsma, Dorret I.; Borgwardt, Stefan; Bourque, Josiane; Brandeis, Daniel; Breier, Alan; Brodaty, Henry; Brouwer, Rachel M.; Buitelaar, Jan K.; Busatto, Geraldo F.; Buckner, Randy L.; Calhoun, Vincent; Canales-Rodríguez, Erick J.; Cannon, Dara M.; Caseras, Xavier; Castellanos, Francisco X.; Cervenka, Simon; Chaim-Avancini, Tiffany M.; Ching, Christopher R.K.; Chubar, Victoria; Clark, Vincent P.; Conrod, Patricia; Conzelmann, Annette; Crespo-Facorro, Benedicto; Crivello, Fabrice; Crone, Eveline A.; Dannlowski, Udo; Dale, Anders M.; Davey, Christopher; de Geus, Eco J.C.; de Haan, Lieuwe; de Zubicaray, Greig I.; den Braber, Anouk; Dickie, Erin W.; Di Giorgio, Annabella; Doan, Nhat Trung; Dørum, Erlend S.; Ehrlich, Stefan; Erk, Susanne; Espeseth, Thomas; Fatouros-Bergman, Helena; Fisher, Simon E.; Fouche, Jean-Paul; Franke, Barbara; Frodl, Thomas; Fuentes-Claramonte, Paola; Glahn, David C.; Gotlib, Ian H.; Grabe, Hans-Jörgen; Grimm, Oliver; Groenewold, Nynke A.; Grotegerd, Dominik; Gruber, Oliver; Gruner, Patricia; Gur, Rachel E.; Gur, Ruben C.; Hahn, Tim; Harrison, Ben J.; Hartman, Catharine A.; Hatton, Sean N.; Heinz, Andreas; Heslenfeld, Dirk J.; Hibar, Derrek P.; Hickie, Ian B.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hohmann, Sarah; Holmes, Avram J.; Hoogman, Martine; Hosten, Norbert; Howells, Fleur M.; Hulshoff Pol, Hilleke E.; Huyser, Chaim; Jahanshad, Neda; James, Anthony; Jernigan, Terry L.; Jiang, Jiyang; Jönsson, Erik G.; Joska, John A.; Kahn, Rene; Kalnin, Andrew; Kanai, Ryota; Klein, Marieke; Klyushnik, Tatyana P.; Koenders, Laura; Koops, Sanne; Krämer, Bernd; Kuntsi, Jonna; Lagopoulos, Jim; Lázaro, Luisa; Lebedeva, Irina; Lee, Won Hee; Lesch, Klaus-Peter; Lochner, Christine; Machielsen, Marise W.J.; Maingault, Sophie; Martin, Nicholas G.; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Mazoyer, Bernard; McDonald, Colm; McDonald, Brenna C.; McIntosh, Andrew M.; McMahon, Katie L.; McPhilemy, Genevieve; Menchón, José M.; Medland, Sarah E.; Meyer-Lindenberg, Andreas; Naaijen, Jilly; Najt, Pablo; Nakao, Tomohiro; Meinert, Susanne; Nordvik, Jan E.; Nyberg, Lars; Oosterlaan, Jaap; Ortiz-García de la Foz, Víctor; Paloyelis, Yannis; Pauli, Paul; Pergola, Giulio; Pomarol-Clotet, Edith; Portella, Maria J.; Potkin, Steven G.; Radua, Joaquim; Reif, Andreas; Rinker, Daniel A.; Roffman, Joshua L.; Rosa, Pedro G.P.; Sacchet, Matthew D.; Sachdev, Perminder S.; Salvador, Raymond; Sánchez-Juan, Pascual; Sarró, Salvador; Satterthwaite, Theodore D.; Saykin, Andrew J.; Serpa, Mauricio H.; Schmaal, Lianne; Schnell, Knut; Schumann, Gunter; Sim, Kang; Smoller, Jordan W.; Sommer, Iris; Soriano-Mas, Carles; Stein, Dan J.; Strike, Lachlan T.; Swagerman, Suzanne C.; Tamnes, Christian K.; Temmingh, Henk S.; Thomopoulos, Sophia I.; Tomyshev, Alexander S.; Tordesillas-Gutiérrez, Diana; Trollor, Julian N.; Turner, Jessica A.; Uhlmann, Anne; van den Heuvel, Odile A.; van den Meer, Dennis; van der Wee, Nic J.A.; van Haren, Neeltje E.M.; van't Ent, Dennis; van Erp, Theo G.M.; Veer, Ilya M.; Veltman, Dick J.; Voineskos, Aristotle; Völzke, Henry; Walter, Henrik; Walton, Esther; Wang, Lei; Wang, Yang; Wassink, Thomas H.; Weber, Bernd; Wen, Wei; West, John D.; Westlye, Lars T.; Whalley, Heather; Wierenga, Lara M.; Williams, Steven C.R.; Wittfeld, Katharina; Wolf, Daniel H.; Worker, Amanda; Wright, Margaret J.; Yang, Kun; Yoncheva, Yulyia; Zanetti, Marcus V.; Ziegler, Georg C.; Thompson, Paul M.; Frangou, Sophia; Karolinska Schizophrenia Project (KaSP); Radiology and Imaging Sciences, School of MedicineAge has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.