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1. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

Author: Schmaal, L, Hibar, DP, Sämann, PG, Hall, GB, Baune, BT, Jahanshad, N, Cheung, JW, van Erp, TGM, Bos, D, Ikram, MA, Vernooij, MW, Niessen, WJ, Tiemeier, H, Hofman, A, Wittfeld, K, Grabe, HJ, Janowitz, D, Bülow, R, Selonke, M, Völzke, H, Grotegerd, D, Dannlowski, U, Arolt, V, Opel, N, Heindel, W, Kugel, H, Hoehn, D, Czisch, M, Couvy-Duchesne, B, Rentería, ME, Strike, LT, Wright, MJ, Mills, NT, de Zubicaray, GI, McMahon, KL, Medland, SE, Martin, NG, Gillespie, NA, Goya-Maldonado, R, Gruber, O, Krämer, B, Hatton, SN, Lagopoulos, J, Hickie, IB, Frodl, T, Carballedo, A, Frey, EM, van Velzen, LS, Penninx, BWJH, van Tol, M-J, van der Wee, NJ, Davey, CG, Harrison, BJ, Mwangi, B, Cao, B, Soares, JC, Veer, IM, Walter, H, Schoepf, D, Zurowski, B, Konrad, C, Schramm, E, Normann, C, Schnell, K, Sacchet, MD, Gotlib, IH, MacQueen, GM, Godlewska, BR, Nickson, T, McIntosh, AM, Papmeyer, M, Whalley, HC, Hall, J, Sussmann, JE, Li, M, Walter, M, Aftanas, L, Brack, I, Bokhan, NA, Thompson, PM, and Veltman, DJ
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Major Depressive Disorder, Serious Mental Illness, Neurosciences, Biomedical Imaging, Depression, Basic Behavioral and Social Science, Mental Health, Brain Disorders, Clinical Research, Pediatric, Behavioral and Social Science, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Adolescent, Adult, Brain, Cerebral Cortex, Depressive Disorder, Major, Female, Frontal Lobe, Gray Matter, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Neuroimaging, Prefrontal Cortex, Temporal Lobe, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
Published: 2017

2. Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

Author: Rentería, ME, Schmaal, L, Hibar, DP, Couvy-Duchesne, B, Strike, LT, Mills, NT, de Zubicaray, GI, McMahon, KL, Medland, SE, Gillespie, NA, Hatton, SN, Lagopoulos, J, Veltman, DJ, van der Wee, N, van Erp, TGM, Wittfeld, K, Grabe, HJ, Block, A, Hegenscheid, K, Völzke, H, Veer, IM, Walter, H, Schnell, K, Schramm, E, Normann, C, Schoepf, D, Konrad, C, Zurowski, B, Godlewska, BR, Cowen, PJ, Penninx, BWJH, Jahanshad, N, Thompson, PM, Wright, MJ, Martin, NG, Christensen, H, and Hickie, IB
Subjects: Brain, Humans, Magnetic Resonance Imaging, Prevalence, Risk Factors, Suicide, Depressive Disorder, Major, Adult, Aged, Middle Aged, Female, Male, Young Adult, Suicidal Ideation, Neuroimaging, Depressive Disorder, Major, Psychology, Clinical Sciences, Public Health and Health Services
Abstract: The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10-3) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.
Published: 2017

3. Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Author: Boen, R, Kaufmann, T, van der Meer, D, Frei, O, Agartz, I, Ames, D, Andersson, M, Armstrong, NJ, Artiges, E, Atkins, JR, Bauer, J, Benedetti, F, Boomsma, DI, Brodaty, H, Brosch, K, Buckner, RL, Cairns, MJ, Calhoun, V, Caspers, S, Cichon, S, Corvin, AP, Crespo-Facorro, B, Dannlowski, U, David, FS, de Geus, EJC, de Zubicaray, GI, Desrivieres, S, Doherty, JL, Donohoe, G, Ehrlich, S, Eising, E, Espeseth, T, Fisher, SE, Forstner, AJ, Fortaner-Uya, L, Frouin, V, Fukunaga, M, Ge, T, Glahn, DC, Goltermann, J, Grabe, HJ, Green, MJ, Groenewold, NA, Grotegerd, D, Grontvedt, GR, Hahn, T, Hashimoto, R, Hehir-Kwa, JY, Henskens, FA, Holmes, AJ, Haberg, AK, Haavik, J, Jacquemont, S, Jansen, A, Jockwitz, C, Joensson, EG, Kikuchi, M, Kircher, T, Kumar, K, Le Hellard, S, Leu, C, Linden, DE, Liu, J, Loughnan, R, Mather, KA, Mcmahon, KL, Mcrae, AF, Medland, SE, Meinert, S, Moreau, CA, Morris, DW, Mowry, BJ, Muehleisen, TW, Nenadic, I, Noethen, MM, Nyberg, L, Ophoff, RA, Owen, MJ, Pantelis, C, Paolini, M, Paus, T, Pausova, Z, Persson, K, Quide, Y, Marques, TR, Sachdev, PS, Sando, SB, Schall, U, Scott, RJ, Selbaek, G, Shumskaya, E, Silva, AI, Sisodiya, SM, Stein, F, Stein, DJ, Straube, B, Streit, F, Strike, LT, Teumer, A, Teutenberg, L, Thalamuthu, A, Tooney, PA, Tordesillas-Gutierrez, D, Trollor, JN, Van't Ent, D, van den Bree, MBM, van Haren, NEM, Vazquez-Bourgon, J, Voelzke, H, Wen, W, Wittfeld, K, Ching, CRK, Westlye, LT, Thompson, PM, Bearden, CE, Selmer, KK, Alnaes, D, Andreassen, OA, Sonderby, IE, Boen, R, Kaufmann, T, van der Meer, D, Frei, O, Agartz, I, Ames, D, Andersson, M, Armstrong, NJ, Artiges, E, Atkins, JR, Bauer, J, Benedetti, F, Boomsma, DI, Brodaty, H, Brosch, K, Buckner, RL, Cairns, MJ, Calhoun, V, Caspers, S, Cichon, S, Corvin, AP, Crespo-Facorro, B, Dannlowski, U, David, FS, de Geus, EJC, de Zubicaray, GI, Desrivieres, S, Doherty, JL, Donohoe, G, Ehrlich, S, Eising, E, Espeseth, T, Fisher, SE, Forstner, AJ, Fortaner-Uya, L, Frouin, V, Fukunaga, M, Ge, T, Glahn, DC, Goltermann, J, Grabe, HJ, Green, MJ, Groenewold, NA, Grotegerd, D, Grontvedt, GR, Hahn, T, Hashimoto, R, Hehir-Kwa, JY, Henskens, FA, Holmes, AJ, Haberg, AK, Haavik, J, Jacquemont, S, Jansen, A, Jockwitz, C, Joensson, EG, Kikuchi, M, Kircher, T, Kumar, K, Le Hellard, S, Leu, C, Linden, DE, Liu, J, Loughnan, R, Mather, KA, Mcmahon, KL, Mcrae, AF, Medland, SE, Meinert, S, Moreau, CA, Morris, DW, Mowry, BJ, Muehleisen, TW, Nenadic, I, Noethen, MM, Nyberg, L, Ophoff, RA, Owen, MJ, Pantelis, C, Paolini, M, Paus, T, Pausova, Z, Persson, K, Quide, Y, Marques, TR, Sachdev, PS, Sando, SB, Schall, U, Scott, RJ, Selbaek, G, Shumskaya, E, Silva, AI, Sisodiya, SM, Stein, F, Stein, DJ, Straube, B, Streit, F, Strike, LT, Teumer, A, Teutenberg, L, Thalamuthu, A, Tooney, PA, Tordesillas-Gutierrez, D, Trollor, JN, Van't Ent, D, van den Bree, MBM, van Haren, NEM, Vazquez-Bourgon, J, Voelzke, H, Wen, W, Wittfeld, K, Ching, CRK, Westlye, LT, Thompson, PM, Bearden, CE, Selmer, KK, Alnaes, D, Andreassen, OA, and Sonderby, IE
Abstract: BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference. RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
Published: 2024

4. Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.

Author: Belov, V, Erwin-Grabner, T, Aghajani, M, Aleman, A, Amod, AR, Basgoze, Z, Benedetti, F, Besteher, B, Bülow, R, Ching, CRK, Connolly, CG, Cullen, K, Davey, CG, Dima, D, Dols, A, Evans, JW, Fu, CHY, Gonul, AS, Gotlib, IH, Grabe, HJ, Groenewold, N, Hamilton, JP, Harrison, BJ, Ho, TC, Mwangi, B, Jaworska, N, Jahanshad, N, Klimes-Dougan, B, Koopowitz, S-M, Lancaster, T, Li, M, Linden, DEJ, MacMaster, FP, Mehler, DMA, Melloni, E, Mueller, BA, Ojha, A, Oudega, ML, Penninx, BWJH, Poletti, S, Pomarol-Clotet, E, Portella, MJ, Pozzi, E, Reneman, L, Sacchet, MD, Sämann, PG, Schrantee, A, Sim, K, Soares, JC, Stein, DJ, Thomopoulos, SI, Uyar-Demir, A, van der Wee, NJA, van der Werff, SJA, Völzke, H, Whittle, S, Wittfeld, K, Wright, MJ, Wu, M-J, Yang, TT, Zarate, C, Veltman, DJ, Schmaal, L, Thompson, PM, Goya-Maldonado, R, ENIGMA Major Depressive Disorder working group, Belov, V, Erwin-Grabner, T, Aghajani, M, Aleman, A, Amod, AR, Basgoze, Z, Benedetti, F, Besteher, B, Bülow, R, Ching, CRK, Connolly, CG, Cullen, K, Davey, CG, Dima, D, Dols, A, Evans, JW, Fu, CHY, Gonul, AS, Gotlib, IH, Grabe, HJ, Groenewold, N, Hamilton, JP, Harrison, BJ, Ho, TC, Mwangi, B, Jaworska, N, Jahanshad, N, Klimes-Dougan, B, Koopowitz, S-M, Lancaster, T, Li, M, Linden, DEJ, MacMaster, FP, Mehler, DMA, Melloni, E, Mueller, BA, Ojha, A, Oudega, ML, Penninx, BWJH, Poletti, S, Pomarol-Clotet, E, Portella, MJ, Pozzi, E, Reneman, L, Sacchet, MD, Sämann, PG, Schrantee, A, Sim, K, Soares, JC, Stein, DJ, Thomopoulos, SI, Uyar-Demir, A, van der Wee, NJA, van der Werff, SJA, Völzke, H, Whittle, S, Wittfeld, K, Wright, MJ, Wu, M-J, Yang, TT, Zarate, C, Veltman, DJ, Schmaal, L, Thompson, PM, Goya-Maldonado, R, and ENIGMA Major Depressive Disorder working group
Abstract: Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
Published: 2024

5. Response to Dr Fried & Dr Kievit, and Dr Malhi et al.

Author: Schmaal, L, Veltman, DJ, van Erp, TGM, Sämann, PG, Frodl, T, Jahanshad, N, Loehrer, E, Vernooij, MW, Niessen, WJ, Ikram, MA, Wittfeld, K, Grabe, HJ, Block, A, Hegenscheid, K, Hoehn, D, Czisch, M, Lagopoulos, J, Hatton, SN, Hickie, IB, Goya-Maldonado, R, Krämer, B, Gruber, O, Couvy-Duchesne, B, Rentería, ME, Strike, LT, Wright, MJ, de Zubicaray, GI, McMahon, KL, Medland, SE, Gillespie, NA, Hall, GB, van Velzen, LS, van Tol, M-J, van der Wee, NJ, Veer, IM, Walter, H, Schramm, E, Normann, C, Schoepf, D, Konrad, C, Zurowski, B, McIntosh, AM, Whalley, HC, Sussmann, JE, Godlewska, BR, Fischer, FH, Penninx, BWJH, Thompson, PM, and Hibar, DP
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Clinical Sciences, Psychology, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Published: 2016

6. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

Author: Schmaal, L, Veltman, DJ, van Erp, TGM, Sämann, PG, Frodl, T, Jahanshad, N, Loehrer, E, Tiemeier, H, Hofman, A, Niessen, WJ, Vernooij, MW, Ikram, MA, Wittfeld, K, Grabe, HJ, Block, A, Hegenscheid, K, Völzke, H, Hoehn, D, Czisch, M, Lagopoulos, J, Hatton, SN, Hickie, IB, Goya-Maldonado, R, Krämer, B, Gruber, O, Couvy-Duchesne, B, Rentería, ME, Strike, LT, Mills, NT, de Zubicaray, GI, McMahon, KL, Medland, SE, Martin, NG, Gillespie, NA, Wright, MJ, Hall, GB, MacQueen, GM, Frey, EM, Carballedo, A, van Velzen, LS, van Tol, MJ, van der Wee, NJ, Veer, IM, Walter, H, Schnell, K, Schramm, E, Normann, C, Schoepf, D, Konrad, C, Zurowski, B, Nickson, T, McIntosh, AM, Papmeyer, M, Whalley, HC, Sussmann, JE, Godlewska, BR, Cowen, PJ, Fischer, FH, Rose, M, Penninx, BWJH, Thompson, PM, and Hibar, DP
Subjects: Brain, Hippocampus, Humans, Magnetic Resonance Imaging, Case-Control Studies, Depressive Disorder, Major, Adult, Middle Aged, Female, Male, Neuroimaging, major depressive disorder, structural volumes, ENIGMA consortium, meta-analysis, hippocampus, Depressive Disorder, Major, Psychiatry, Medical and Health Sciences, Biological Sciences, Psychology and Cognitive Sciences
Abstract: The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.
Published: 2016

7. P-101 Exploring the dynamics between brain and heart in the Study of Health in Pomerania

Author: Krause, E., primary, Wittfeld, K., additional, Vollmer, M., additional, Dörr, M., additional, Felix, S., additional, Stubbe, B., additional, Ewert, R., additional, Völzke, H., additional, and Grabe, H., additional
Published: 2023
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8. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

Author: Groenewold, NA, Bas-Hoogendam, JM, Amod, AR, Laansma, MA, Van Velzen, LS, Aghajani, M, Hilbert, K, Oh, H, Salas, R, Jackowski, AP, Pan, PM, Salum, GA, Blair, JR, Blair, KS, Hirsch, J, Pantazatos, SP, Schneier, FR, Talati, A, Roelofs, K, Volman, I, Blanco-Hinojo, L, Cardoner, N, Pujol, J, Beesdo-Baum, K, Ching, CRK, Thomopoulos, SI, Jansen, A, Kircher, T, Krug, A, Nenadić, I, Stein, F, Dannlowski, U, Grotegerd, D, Lemke, H, Meinert, S, Winter, A, Erb, M, Kreifelts, B, Gong, Q, Lui, S, Zhu, F, Mwangi, B, Soares, JC, Wu, M-J, Bayram, A, Canli, M, Tükel, R, Westenberg, PM, Heeren, A, Cremers, HR, Hofmann, D, Straube, T, Doruyter, AGG, Lochner, C, Peterburs, J, Van Tol, M-J, Gur, RE, Kaczkurkin, AN, Larsen, B, Satterthwaite, TD, Filippi, CA, Gold, AL, Harrewijn, A, Zugman, A, Bülow, R, Grabe, HJ, Völzke, H, Wittfeld, K, Böhnlein, J, Dohm, K, Kugel, H, Schrammen, E, Zwanzger, P, Leehr, EJ, Sindermann, L, Ball, TM, Fonzo, GA, Paulus, MP, Simmons, A, Stein, MB, Klumpp, H, Phan, KL, Furmark, T, Månsson, KNT, Manzouri, A, Avery, SN, Blackford, JU, Clauss, JA, Feola, B, Harper, JC, Sylvester, CM, Lueken, U, Veltman, DJ, Winkler, AM, Jahanshad, N, Pine, DS, Thompson, PM, Stein, DJ, Van der Wee, NJA, Groenewold, NA, Bas-Hoogendam, JM, Amod, AR, Laansma, MA, Van Velzen, LS, Aghajani, M, Hilbert, K, Oh, H, Salas, R, Jackowski, AP, Pan, PM, Salum, GA, Blair, JR, Blair, KS, Hirsch, J, Pantazatos, SP, Schneier, FR, Talati, A, Roelofs, K, Volman, I, Blanco-Hinojo, L, Cardoner, N, Pujol, J, Beesdo-Baum, K, Ching, CRK, Thomopoulos, SI, Jansen, A, Kircher, T, Krug, A, Nenadić, I, Stein, F, Dannlowski, U, Grotegerd, D, Lemke, H, Meinert, S, Winter, A, Erb, M, Kreifelts, B, Gong, Q, Lui, S, Zhu, F, Mwangi, B, Soares, JC, Wu, M-J, Bayram, A, Canli, M, Tükel, R, Westenberg, PM, Heeren, A, Cremers, HR, Hofmann, D, Straube, T, Doruyter, AGG, Lochner, C, Peterburs, J, Van Tol, M-J, Gur, RE, Kaczkurkin, AN, Larsen, B, Satterthwaite, TD, Filippi, CA, Gold, AL, Harrewijn, A, Zugman, A, Bülow, R, Grabe, HJ, Völzke, H, Wittfeld, K, Böhnlein, J, Dohm, K, Kugel, H, Schrammen, E, Zwanzger, P, Leehr, EJ, Sindermann, L, Ball, TM, Fonzo, GA, Paulus, MP, Simmons, A, Stein, MB, Klumpp, H, Phan, KL, Furmark, T, Månsson, KNT, Manzouri, A, Avery, SN, Blackford, JU, Clauss, JA, Feola, B, Harper, JC, Sylvester, CM, Lueken, U, Veltman, DJ, Winkler, AM, Jahanshad, N, Pine, DS, Thompson, PM, Stein, DJ, and Van der Wee, NJA
Abstract: There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
Published: 2023

9. Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease.

Author: Duperron, M-G, Knol, MJ, Le Grand, Q, Evans, TE, Mishra, A, Tsuchida, A, Roshchupkin, G, Konuma, T, Trégouët, D-A, Romero, JR, Frenzel, S, Luciano, M, Hofer, E, Bourgey, M, Dueker, ND, Delgado, P, Hilal, S, Tankard, RM, Dubost, F, Shin, J, Saba, Y, Armstrong, NJ, Bordes, C, Bastin, ME, Beiser, A, Brodaty, H, Bülow, R, Carrera, C, Chen, C, Cheng, C-Y, Deary, IJ, Gampawar, PG, Himali, JJ, Jiang, J, Kawaguchi, T, Li, S, Macalli, M, Marquis, P, Morris, Z, Muñoz Maniega, S, Miyamoto, S, Okawa, M, Paradise, M, Parva, P, Rundek, T, Sargurupremraj, M, Schilling, S, Setoh, K, Soukarieh, O, Tabara, Y, Teumer, A, Thalamuthu, A, Trollor, JN, Valdés Hernández, MC, Vernooij, MW, Völker, U, Wittfeld, K, Wong, TY, Wright, MJ, Zhang, J, Zhao, W, Zhu, Y-C, Schmidt, H, Sachdev, PS, Wen, W, Yoshida, K, Joutel, A, Satizabal, CL, Sacco, RL, Bourque, G, CHARGE consortium, Lathrop, M, Paus, T, Fernandez-Cadenas, I, Yang, Q, Mazoyer, B, Boutinaud, P, Okada, Y, Grabe, HJ, Mather, KA, Schmidt, R, Joliot, M, Ikram, MA, Matsuda, F, Tzourio, C, Wardlaw, JM, Seshadri, S, Adams, HHH, Debette, S, Duperron, M-G, Knol, MJ, Le Grand, Q, Evans, TE, Mishra, A, Tsuchida, A, Roshchupkin, G, Konuma, T, Trégouët, D-A, Romero, JR, Frenzel, S, Luciano, M, Hofer, E, Bourgey, M, Dueker, ND, Delgado, P, Hilal, S, Tankard, RM, Dubost, F, Shin, J, Saba, Y, Armstrong, NJ, Bordes, C, Bastin, ME, Beiser, A, Brodaty, H, Bülow, R, Carrera, C, Chen, C, Cheng, C-Y, Deary, IJ, Gampawar, PG, Himali, JJ, Jiang, J, Kawaguchi, T, Li, S, Macalli, M, Marquis, P, Morris, Z, Muñoz Maniega, S, Miyamoto, S, Okawa, M, Paradise, M, Parva, P, Rundek, T, Sargurupremraj, M, Schilling, S, Setoh, K, Soukarieh, O, Tabara, Y, Teumer, A, Thalamuthu, A, Trollor, JN, Valdés Hernández, MC, Vernooij, MW, Völker, U, Wittfeld, K, Wong, TY, Wright, MJ, Zhang, J, Zhao, W, Zhu, Y-C, Schmidt, H, Sachdev, PS, Wen, W, Yoshida, K, Joutel, A, Satizabal, CL, Sacco, RL, Bourque, G, CHARGE consortium, Lathrop, M, Paus, T, Fernandez-Cadenas, I, Yang, Q, Mazoyer, B, Boutinaud, P, Okada, Y, Grabe, HJ, Mather, KA, Schmidt, R, Joliot, M, Ikram, MA, Matsuda, F, Tzourio, C, Wardlaw, JM, Seshadri, S, Adams, HHH, and Debette, S
Abstract: Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.
Published: 2023

10. New insights into the genetic etiology of Alzheimer's disease and related dementias

Author: Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. A., Piñol-Ripoll, G., Pisanu, C., Polak, T., Popp, J., Posthuma, D., Priller, J., Puerta, R., Quenez, O., Quintela, I., Thomassen, J. Q., Rábano, A., Rainero, I., Rajabli, F., Ramakers, I., Real, L. M., Reinders, M. J. T., Reitz, C., Reyes-Dumeyer, D., Ridge, P., Riedel-Heller, S., Riederer, P., Roberto, N., Rodriguez-Rodriguez, E., Rongve, A., Allende, I. R., Rosende-Roca, M., Royo, J. L., Rubino, E., Rujescu, D., Sáez, M. E., Sakka, P., Saltvedt, I., Sanabria, Á., Sánchez-Arjona, M. B., Sanchez-Garcia, F., Juan, P. S., Sánchez-Valle, R., Sando, S. B., Sarnowski, C., Satizabal, C. L., Scamosci, M., Scarmeas, N., Scarpini, E., Scheltens, P., Scherbaum, N., Scherer, M., Schmid, M., Schneider, A., Schott, J. M., Selbæk, G., Seripa, D., Serrano, M., Sha, J., Shadrin, A. A., Skrobot, O., Slifer, S., Snijders, G. J. L., Soininen, H., Solfrizzi, V., Solomon, A., Song, Y. E., Sorbi, S., Sotolongo-Grau, O., Spalletta, G., Spottke, A., Squassina, A., Stordal, E., Tartan, J. 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S., Collinge, J., Craig, D., Deloukas, P., Fox, N., Gerrish, A., Gill, M., Gwilliam, R., Harold, D., Hollingworth, P., Johnston, J. A., Jones, L., Lawlor, B., Livingston, G., Lovestone, S., Lupton, M., Lynch, A., Mann, D., Mcguinness, B., Mcquillin, A., O’Donovan, M. C., Owen, M. J., Passmore, P., Powell, J. F., Proitsi, P., Rossor, M., Shaw, C. E., Smith, A. D., Gurling, H., Todd, S., Mummery, C., Ryan, N., Lacidogna, G., Adarmes-Gómez, A., Mauleón, A., Pancho, A., Gailhajenet, A., Lafuente, A., Macias-García, D., Martín, E., Pelejà, E., Carrillo, F., Merlín, I. S., Garrote-Espina, L., Vargas, L., Carrion-Claro, M., Marín, M., Labrador, M., Buendia, M., Alonso, M. D., Guitart, M., Moreno, M., Ibarria, M., Periñán, M., Aguilera, N., Gómez-Garre, P., Cañabate, P., Escuela, R., Pineda-Sánchez, R., Vigo-Ortega, R., Jesús, S., Preckler, S., Rodrigo-Herrero, S., Diego, S., Vacca, A., Roveta, F., Salvadori, N., Chipi, E., Boecker, H., Laske, C., Perneczky, R., Anastasiou, C., Janowitz, D., Malik, R., Anastasiou, A., Parveen, K., López-García, S., Antonell, A., Mihova, K. Y., Belezhanska, D., Weber, H., Kochen, S., Solis, P., Medel, N., Lisso, J., Sevillano, Z., Politis, D. G., Cores, V., Cuesta, C., Ortiz, C., Bacha, J. I., Rios, M., Saenz, A., Abalos, M. S., Kohler, E., Palacio, D. L., Etchepareborda, I., Kohler, M., Novack, G., Prestia, F. A., Galeano, P., Castaño, E. M., Germani, S., Toso, C. R., Rojo, M., Ingino, C., Mangone, C., Rubinsztein, D. C., Teipel, S., Fievet, N., Deramerourt, V., Forsell, C., Thonberg, H., Bjerke, M., Roeck, E. D., Martínez-Larrad, M. 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M., Pickering-Brown, S., Sussams, R., Warner, N., Bayer, A., Heuser, I., Drichel, D., Klopp, N., Mayhaus, M., Riemenschneider, M., Pinchler, S., Feulner, T., Gu, W., van den Bussche, H., Hüll, M., Frölich, L., Wichmann, H. -E., Jöckel, K. -H., O’Donovan, M., Owen, M., Bahrami, S., Bosnes, I., Selnes, P., Bergh, S., Palotie, A., Daly, M., Jacob, H., Matakidou, A., Runz, H., John, S., Plenge, R., Mccarthy, M., Hunkapiller, J., Ehm, M., Waterworth, D., Fox, C., Malarstig, A., Klinger, K., Call, K., Behrens, T., Loerch, P., Mäkelä, T., Kaprio, J., Virolainen, P., Pulkki, K., Kilpi, T., Perola, M., Partanen, J., Pitkäranta, A., Kaarteenaho, R., Vainio, S., Turpeinen, M., Serpi, R., Laitinen, T., Mäkelä, J., Kosma, V. -M., Kujala, U., Tuovila, O., Hendolin, M., Pakkanen, R., Waring, J., Riley-Gillis, B., Liu, J., Biswas, S., Diogo, D., Marshall, C., Hu, X., Gossel, M., Graham, R., Cummings, B., Ripatti, S., Schleutker, J., Arvas, M., Carpén, O., Hinttala, R., Kettunen, J., Mannermaa, A., Laukkanen, J., Julkunen, V., Remes, A., Kälviäinen, R., Peltola, J., Tienari, P., Rinne, J., Ziemann, A., Esmaeeli, S., Smaoui, N., Lehtonen, A., Eaton, S., Lahdenperä, S., van Adelsberg, J., Michon, J., Kerchner, G., Bowers, N., Teng, E., Eicher, J., Mehta, V., Gormley, P., Linden, K., Whelan, C., Xu, F., Pulford, D., Färkkilä, M., Pikkarainen, S., Jussila, A., Blomster, T., Kiviniemi, M., Voutilainen, M., Georgantas, B., Heap, G., Rahimov, F., Usiskin, K., Lu, T., Oh, D., Kalpala, K., Miller, M., Mccarthy, L., Eklund, K., Palomäki, A., Isomäki, P., Pirilä, L., Kaipiainen-Seppänen, O., Huhtakangas, J., Lertratanakul, A., Hochfeld, M., Bing, N., Gordillo, J. 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P., Brein, G., Awaisa, G., Shcherban, A., Donner, K., Loukola, A., Laiho, P., Sistonen, T., Kaiharju, E., Laukkanen, M., Järvensivu, E., Lähteenmäki, S., Männikkö, L., Wong, R., Mattsson, H., Hiekkalinna, T., Paajanen, T., Pärn, K., Gracia-Tabuenca, J., Abner, E., Adams, P. M., Aguirre, A., Albert, M. S., Albin, R. L., Allen, M., Alvarez, L., Apostolova, L. G., Arnold, S. E., Asthana, S., Atwood, C. S., Ayres, G., Baldwin, C. T., Barber, R. C., Barnes, L. L., Beach, T. G., Becker, J. T., Beecham, G. W., Beekly, D., Benitez, B. A., Bennett, D., Bertelson, J., Margaret, F. E., Bird, T. D., Blacker, D., Boeve, B. F., Bowen, J. D., Boxer, A., Brewer, J., Burke, J. R., Burns, J. M., Buxbaum, J. D., Cairns, N. J., Cao, C., Carlson, C. S., Carlsson, C. M., Carney, R. M., Carrasquillo, M. M., Chasse, S., Chesselet, M. -F., Chesi, A., Chin, N. A., Chui, H. C., Craft, S., Crane, P. K., Cribbs, D. H., Crocco, E. A., Cruchaga, C., Cullum, M., Darby, E., Davis, B., De Jager, P. 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M, Rossi, P, Djurovic, S, Duron, E, Düzel, E, Dufouil, C, Eiriksdottir, G, Engelborghs, S, Escott-Price, V, Espinosa, A, Ewers, M, Faber, K, Fabrizio, T, Nielsen, S, Fardo, D, Farotti, L, Fenoglio, C, Fernández-Fuertes, M, Ferrari, R, Ferreira, C, Ferri, E, Fin, B, Fischer, P, Fladby, T, Fließbach, K, Fongang, B, Fornage, M, Fortea, J, Foroud, T, Fostinelli, S, Fox, N, Franco-Macías, E, Bullido, M, Frank-García, A, Froelich, L, Fulton-Howard, B, Galimberti, D, García-Alberca, J, García-González, P, Garcia-Madrona, S, Garcia-Ribas, G, Ghidoni, R, Giegling, I, Giorgio, G, Goate, A, Goldhardt, O, Gomez-Fonseca, D, González-Pérez, A, Graff, C, Grande, G, Green, E, Grimmer, T, Grünblatt, E, Grunin, M, Gudnason, V, Guetta-Baranes, T, Haapasalo, A, Hadjigeorgiou, G, Haines, J, Hamilton-Nelson, K, Hampel, H, Hanon, O, Hardy, J, Hartmann, A, Hausner, L, Harwood, J, Heilmann-Heimbach, S, Helisalmi, S, Heneka, M, Hernández, I, Herrmann, M, Hoffmann, P, Holmes, C, Holstege, H, Vilas, R, Hulsman, M, Humphrey, J, Biessels, G, Jian, X, Johansson, C, Jun, G, Kastumata, Y, Kauwe, J, Kehoe, P, Kilander, L, Ståhlbom, A, Kivipelto, M, Koivisto, A, Kornhuber, J, Kosmidis, M, Kukull, W, Kuksa, P, Kunkle, B, Kuzma, A, Lage, C, Laukka, E, Launer, L, Lauria, A, Lee, C, Lehtisalo, J, Lerch, O, Lleó, A, Longstreth, W, Lopez, O, de Munain, A, Love, S, Löwemark, M, Luckcuck, L, Lunetta, K, Ma, Y, Macías, J, Macleod, C, Maier, W, Mangialasche, F, Spallazzi, M, Marquié, M, Marshall, R, Martin, E, Montes, A, Rodríguez, C, Masullo, C, Mayeux, R, Mead, S, Mecocci, P, Medina, M, Meggy, A, Mehrabian, S, Mendoza, S, Menéndez-González, M, Mir, P, Moebus, S, Mol, M, Molina-Porcel, L, Montrreal, L, Morelli, L, Moreno, F, Morgan, K, Mosley, T, Nöthen, M, Muchnik, C, Mukherjee, S, Nacmias, B, Ngandu, T, Nicolas, G, Nordestgaard, B, Olaso, R, Orellana, A, Orsini, M, Ortega, G, Padovani, A, Paolo, C, Papenberg, G, Parnetti, L, Pasquier, F, Pastor, P, Peloso, G, Pérez-Cordón, A, Pérez-Tur, J, Pericard, P, Peters, O, Pijnenburg, Y, Pineda, J, Piñol-Ripoll, G, Pisanu, C, Polak, T, Popp, J, Posthuma, D, Priller, J, Puerta, R, Quenez, O, Quintela, I, Thomassen, J, Rábano, A, Rainero, I, Rajabli, F, Ramakers, I, Real, L, Reinders, M, Reitz, C, Reyes-Dumeyer, D, Ridge, P, Riedel-Heller, S, Riederer, P, Roberto, N, Rodriguez-Rodriguez, E, Rongve, A, Allende, I, Rosende-Roca, M, Royo, J, Rubino, E, Rujescu, D, Sáez, M, Sakka, P, Saltvedt, I, Sanabria, Á, Sánchez-Arjona, M, Sanchez-Garcia, F, Juan, P, Sánchez-Valle, R, Sando, S, Sarnowski, C, Satizabal, C, Scamosci, M, Scarmeas, N, Scarpini, E, Scheltens, P, Scherbaum, N, Scherer, M, Schmid, M, Schneider, A, Schott, J, Selbæk, G, Seripa, D, Serrano, M, Sha, J, Shadrin, A, Skrobot, O, Slifer, S, Snijders, G, Soininen, H, Solfrizzi, V, Solomon, A, Song, Y, Sorbi, S, Sotolongo-Grau, O, Spalletta, G, Spottke, A, Squassina, A, Stordal, E, Tartan, J, Tárraga, L, Tesí, N, Thalamuthu, A, Thomas, T, Tosto, G, Traykov, L, Tremolizzo, L, Tybjærg-Hansen, A, Uitterlinden, A, Ullgren, A, Ulstein, I, Valero, S, Valladares, O, Broeckhoven, C, Vance, J, Vardarajan, B, van der Lugt, A, Dongen, J, van Rooij, J, van Swieten, J, Vandenberghe, R, Verhey, F, Vidal, J, Vogelgsang, J, Vyhnalek, M, Wagner, M, Wallon, D, Wang, L, Wang, R, Weinhold, L, Wiltfang, J, Windle, G, Woods, B, Yannakoulia, M, Zare, H, Zhao, Y, Zhang, X, Zhu, C, Zulaica, M, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Farrer, L, Psaty, B, Ghanbari, M, Raj, T, Sachdev, P, Mather, K, Jessen, F, Ikram, M, de Mendonça, A, Hort, J, Tsolaki, M, Pericak-Vance, M, Amouyel, P, Williams, J, Frikke-Schmidt, R, Clarimon, J, Deleuze, J, Rossi, G, Seshadri, S, Andreassen, O, Ingelsson, M, Hiltunen, M, Sleegers, K, Schellenberg, G, van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, VU University medical center, Amsterdam Neuroscience - Neurodegeneration, Neurology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, APH - Personalized Medicine, APH - Methodology, Bellenguez, Céline [0000-0002-1240-7874], Küçükali, Fahri [0000-0002-3835-9639], Amin, Najaf [0000-0002-8944-1771], Holmans, Peter A [0000-0003-0870-9412], van der Lee, Sven J [0000-0003-1606-8643], Costa, Marcos R [0000-0002-4928-2163], Kuulasmaa, Teemu [0000-0002-1795-7314], Yang, Qiong [0000-0002-3658-1375], de Rojas, Itziar [0000-0002-2148-381X], Bis, Joshua C [0000-0002-3409-1110], Yaqub, Amber [0000-0002-3579-8054], Prokic, Ivana [0000-0002-0370-1473], Chapuis, Julien [0000-0002-5802-2857], Ahmad, Shahzad [0000-0002-8658-3790], Giedraitis, Vilmantas [0000-0003-3423-2021], Garcia-Gonzalez, Pablo [0000-0003-0125-5403], Alcolea, Daniel [0000-0002-3819-3245], Alvarez, Ignacio [0000-0002-8537-3935], Tsolaki, Anthoula [0000-0002-5563-7776], Baquero, Miquel [0000-0002-6861-1831], Pastor, Ana Belén [0000-0001-9637-4688], Berr, Claudine [0000-0001-5254-7655], Bessi, Valentina [0000-0002-6176-3584], Boada, Mercè [0000-0003-2617-3009], Bossù, Paola [0000-0002-1432-0078], Bråthen, Geir [0000-0003-3224-7983], Bressler, Jan [0000-0001-6578-4772], Bresner, Catherine [0000-0003-2673-9762], Brodaty, Henry [0000-0001-9487-6617], Brookes, Keeley J [0000-0003-2427-2513], Burholt, Vanessa [0000-0002-6789-127X], Bush, William S [0000-0002-9729-6519], Calero, Miguel [0000-0001-5366-3324], Chung, Jaeyoon [0000-0002-6431-9454], Cervera-Carles, Laura [0000-0003-2286-200X], Costantini, Emanuele [0000-0002-1096-8221], Dalmasso, Maria Carolina [0000-0002-4901-9955], de Paiva Lopes, Katia [0000-0002-0240-0126], de Witte, Lot D [0000-0002-7235-9958], Debette, Stéphanie [0000-0001-8675-7968], Del Ser, Teodoro [0000-0001-9806-7083], Dichgans, Martin [0000-0002-0654-387X], Diehl-Schmid, Janine [0000-0002-7745-1382], Diez-Fairen, Mónica [0000-0003-1882-0309], Djurovic, Srdjan [0000-0002-8140-8061], Dufouil, Carole [0000-0003-2442-4476], Escott-Price, Valentina [0000-0003-1784-5483], Ewers, Michael [0000-0001-5231-1714], Fabrizio, Tagliavini [0000-0003-1039-7315], Fladby, Tormod [0000-0002-9984-9797], Fornage, Myriam [0000-0003-0677-8158], Fox, Nick C [0000-0002-6660-657X], Bullido, María J [0000-0002-6477-1117], Froelich, Lutz [0000-0003-1494-0813], Galimberti, Daniela [0000-0002-9284-5953], García-Alberca, Jose Maria [0000-0003-2951-6644], Goate, Alison M [0000-0002-0576-2472], González-Pérez, Antonio [0000-0001-9771-5982], Green, Emma [0000-0002-8687-5590], Grünblatt, Edna [0000-0001-8505-7265], Gudnason, Vilmundur [0000-0001-5696-0084], Haapasalo, Annakaisa [0000-0003-0959-2957], Harwood, Janet [0000-0002-3225-0069], Heilmann-Heimbach, Stefanie [0000-0003-1057-465X], Herrmann, Martin J [0000-0001-9970-2122], Holstege, Henne [0000-0002-7688-3087], Biessels, Geert Jan [0000-0001-6862-2496], Jian, Xueqiu [0000-0002-0313-6494], Johansson, Charlotte [0000-0002-5351-1950], Jun, Gyungah R [0000-0002-3230-8697], Kastumata, Yuriko [0000-0002-0188-8094], Kehoe, Patrick G [0000-0002-7542-1139], Kornhuber, Johannes [0000-0002-8096-3987], Kosmidis, Mary H [0000-0001-8790-1220], Lage, Carmen [0000-0003-1703-121X], Launer, Lenore [0000-0002-3238-7612], Lee, Chien-Yueh [0000-0002-4304-974X], Lleó, Alberto [0000-0002-2568-5478], Lopez, Oscar [0000-0002-8546-8256], de Munain, Adolfo Lopez [0000-0002-9509-4032], Lunetta, Kathryn L [0000-0002-9268-810X], Ma, Yiyi [0000-0002-3609-8877], MacLeod, Catherine A [0000-0002-9314-7380], Marquié, Marta [0000-0002-0660-0950], Montes, Angel Martín [0000-0002-1694-786X], Mead, Simon [0000-0002-4326-1468], Medina, Miguel [0000-0002-7016-5340], Menéndez-González, Manuel [0000-0002-5218-0774], Mol, Merel [0000-0003-2533-2530], Morgan, Kevin [0000-0002-8217-2396], Nöthen, Markus M [0000-0002-8770-2464], Muchnik, Carolina [0000-0002-1542-3706], Nacmias, Benedetta [0000-0001-9338-9040], Nicolas, Gael [0000-0001-9391-7800], Nordestgaard, Børge G [0000-0002-1954-7220], Pasquier, Florence [0000-0001-9880-9788], Pastor, Pau [0000-0002-7493-8777], Peloso, Gina [0000-0002-5355-8636], Pérez-Cordón, Alba [0000-0002-6028-0791], Pérez-Tur, Jordi [0000-0002-9111-1712], Pericard, Pierre [0000-0001-8167-6448], Pineda, Juan A [0000-0002-3751-0296], Pisanu, Claudia [0000-0002-9151-4319], Posthuma, Danielle [0000-0001-7582-2365], Puerta, Raquel [0000-0002-1191-5893], Quenez, Olivier [0000-0002-8273-8505], Thomassen, Jesper Qvist [0000-0003-3484-9531], Real, Luis M [0000-0003-4932-7429], Reinders, Marcel JT [0000-0002-1148-1562], Reitz, Christiane [0000-0001-8757-7889], Riedel-Heller, Steffi [0000-0003-4321-6090], Rodriguez-Rodriguez, Eloy [0000-0001-7742-677X], Rongve, Arvid [0000-0002-0476-4134], Sáez, María Eugenia [0000-0001-9299-2534], Saltvedt, Ingvild [0000-0002-7897-9808], Juan, Pascual Sánchez [0000-0002-6081-8037], Sarnowski, Chloé [0000-0002-6090-7099], Satizabal, Claudia L [0000-0002-1115-4430], Schott, Jonathan M [0000-0003-2059-024X], Selbæk, Geir [0000-0001-6511-8219], Shadrin, Alexey A [0000-0002-7467-250X], Soininen, Hilkka [0000-0002-2785-9937], Solfrizzi, Vincenzo [0000-0002-8524-0315], Song, Yeunjoo [0000-0002-7452-3731], Sotolongo-Grau, Oscar [0000-0002-9679-0670], Spalletta, Gianfranco [0000-0002-7432-4249], Squassina, Alessio [0000-0001-7415-7607], Stordal, Eystein [0000-0002-2443-7923], Tosto, Giuseppe [0000-0001-7075-8245], Uitterlinden, Andre [0000-0002-7276-3387], Valladares, Otto [0000-0001-8055-2187], Broeckhoven, Christine Van [0000-0003-0183-7665], Vidal, Jean-Sébastien [0000-0001-6770-0720], Vogelgsang, Jonathan [0000-0001-9326-8193], Wagner, Michael [0000-0003-2589-6440], Wallon, David [0000-0002-2634-7198], Wiltfang, Jens [0000-0003-1492-5330], Woods, Bob [0000-0002-6781-651X], Yannakoulia, Mary [0000-0003-2171-7337], Zare, Habil [0000-0001-5902-6238], Zhang, Xiaoling [0000-0001-8237-1857], Farrer, Lindsay A [0000-0001-5533-4225], Psaty, Bruce M [0000-0002-7278-2190], Ghanbari, Mohsen [0000-0002-9476-7143], Raj, Towfique [0000-0002-9355-5704], Sachdev, Perminder [0000-0002-9595-3220], Mather, Karen [0000-0003-4143-8941], Ikram, M Arfan [0000-0003-0372-8585], Tsolaki, Magda [0000-0002-2072-8010], Pericak-Vance, Margaret A [0000-0001-7283-8804], Amouyel, Philippe [0000-0001-9088-234X], Williams, Julie [0000-0002-4069-0259], Frikke-Schmidt, Ruth [0000-0003-4084-5027], Seshadri, Sudha [0000-0001-6135-2622], Andreassen, Ole A [0000-0002-4461-3568], Sleegers, Kristel [0000-0002-0283-2332], van Duijn, Cornelia M [0000-0002-2374-9204], Sims, Rebecca [0000-0002-3885-1199], van der Flier, Wiesje M [0000-0001-8766-6224], Ramirez, Alfredo [0000-0003-4991-763X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Complex Trait Genetics, Clinical sciences, Neuroprotection & Neuromodulation, Pathologic Biochemistry and Physiology, Clinical Biology, Epidemiology, Internal Medicine, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
Subjects: tau Proteins/genetics, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], Neurologi, MED/03 - GENETICA MEDICA, 45/43, Medizin, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], genetics [Alzheimer Disease], Genome-Wide Association Study, Humans, tau Proteins, Alzheimer Disease, Cognitive Dysfunction, VARIANTS, pathology [Alzheimer Disease], Tau Proteins, Settore BIO/13 - Biologia Applicata, Cognitive Dysfunction/psychology, 692/699/375/365/1283, IMPUTATION, article, 1184 Genetics, developmental biology, physiology, Biología y Biomedicina / Biología, AMYLOID-BETA, Settore MED/26 - NEUROLOGIA, Neurology, psychology [Cognitive Dysfunction], Medical Genetics, Human, Neuroscience(all), 631/208/205/2138, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:570, Genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, Medicinsk genetik, MED/26 - NEUROLOGIA, Alzheimer Disease/genetics, neurology, tau Protein, NECROSIS-FACTOR-ALPHA, RISK LOCI, genetics [tau Proteins], PREDICTION MODELS, Human medicine, GENERATION, RESPONSES
Abstract: 25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
Published: 2022

11. BDNF Val66Met polymorphism and hippocampal volume in neuropsychiatric disorders: A systematic review and meta-analysis

Author: Harrisberger, F., Smieskova, R., Schmidt, A., Lenz, C., Walter, A., Wittfeld, K., Grabe, H.J., Lang, U.E., Fusar-Poli, P., and Borgwardt, S.
Published: 2015
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12. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author: Brouwer, RM, Klein, M, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alanaes, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Boen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bulow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivieres, S, Diaz-Caneja, CM, Doan, NT, Dohm, K, Froehner, JH, Goltermann, J, Grigis, A, Grotegerd, D, Han, LKM, Harris, MA, Hartman, CA, Heany, SJ, Heindel, W, Heslenfeld, DJ, Hohmann, S, Ittermann, B, Jansen, PR, Janssen, J, Jia, T, Jiang, J, Jockwitz, C, Karali, T, Keeser, D, Koevoets, MGJC, Lenroot, RK, Malchow, B, Mandl, RCW, Medel, V, Meinert, S, Morgan, CA, Muehleisen, TW, Nabulsi, L, Opel, N, de la Foz, VO-G, Overs, BJ, Paillere Martinot, M-L, Redlich, R, Marques, TR, Repple, J, Roberts, G, Roshchupkin, GV, Setiaman, N, Shumskaya, E, Stein, F, Sudre, G, Takahashi, S, Thalamuthu, A, Tordesillas-Gutierrez, D, van der Lugt, A, van Haren, NEM, Wardlaw, JM, Wen, W, Westeneng, H-J, Wittfeld, K, Zhu, AH, Zugman, A, Armstrong, NJ, Bonfiglio, G, Bralten, J, Dalvie, S, Davies, G, Di Forti, M, Ding, L, Donohoe, G, Forstner, AJ, Gonzalez-Penas, J, Guimaraes, JPOFT, Homuth, G, Hottenga, J-J, Knol, MJ, Kwok, JBJ, Le Hellard, S, Mather, KA, Milaneschi, Y, Morris, DW, Noethen, MM, Papiol, S, Rietschel, M, Santoro, ML, Steen, VM, Stein, JL, Streit, F, Tankard, RM, Teumer, A, van 't Ent, D, van der Meer, D, van Eijk, KR, Vassos, E, Vazquez-Bourgon, J, Witt, SH, Adams, HHH, Agartz, I, Ames, D, Amunts, K, Andreassen, OA, Arango, C, Banaschewski, T, Baune, BT, Belangero, SI, Bokde, ALW, Boomsma, DI, Bressan, RA, Brodaty, H, Buitelaar, JK, Cahn, W, Caspers, S, Cichon, S, Crespo-Facorro, B, Cox, SR, Dannlowski, U, Elvsashagen, T, Espeseth, T, Falkai, PG, Fisher, SE, Flor, H, Fullerton, JM, Garavan, H, Gowland, PA, Grabe, HJ, Hahn, T, Heinz, A, Hillegers, M, Hoare, J, Hoekstra, PJ, Ikram, MA, Jackowski, AP, Jansen, A, Jonsson, EG, Kahn, RS, Kircher, T, Korgaonkar, MS, Krug, A, Lemaitre, H, Malt, UF, Martinot, J-L, McDonald, C, Mitchell, PB, Muetzel, RL, Murray, RM, Nees, F, Nenadic, I, Oosterlaan, J, Ophoff, RA, Pan, PM, Penninx, BWJH, Poustka, L, Sachdev, PS, Salum, GA, Schofield, PR, Schumann, G, Shaw, P, Sim, K, Smolka, MN, Stein, DJ, Trollor, JN, van den Berg, LH, Veldink, JH, Walter, H, Westlye, LT, Whelan, R, White, T, Wright, MJ, Medland, SE, Franke, B, Thompson, PM, Hulshoff Pol, HE, Brouwer, RM, Klein, M, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alanaes, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Boen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bulow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivieres, S, Diaz-Caneja, CM, Doan, NT, Dohm, K, Froehner, JH, Goltermann, J, Grigis, A, Grotegerd, D, Han, LKM, Harris, MA, Hartman, CA, Heany, SJ, Heindel, W, Heslenfeld, DJ, Hohmann, S, Ittermann, B, Jansen, PR, Janssen, J, Jia, T, Jiang, J, Jockwitz, C, Karali, T, Keeser, D, Koevoets, MGJC, Lenroot, RK, Malchow, B, Mandl, RCW, Medel, V, Meinert, S, Morgan, CA, Muehleisen, TW, Nabulsi, L, Opel, N, de la Foz, VO-G, Overs, BJ, Paillere Martinot, M-L, Redlich, R, Marques, TR, Repple, J, Roberts, G, Roshchupkin, GV, Setiaman, N, Shumskaya, E, Stein, F, Sudre, G, Takahashi, S, Thalamuthu, A, Tordesillas-Gutierrez, D, van der Lugt, A, van Haren, NEM, Wardlaw, JM, Wen, W, Westeneng, H-J, Wittfeld, K, Zhu, AH, Zugman, A, Armstrong, NJ, Bonfiglio, G, Bralten, J, Dalvie, S, Davies, G, Di Forti, M, Ding, L, Donohoe, G, Forstner, AJ, Gonzalez-Penas, J, Guimaraes, JPOFT, Homuth, G, Hottenga, J-J, Knol, MJ, Kwok, JBJ, Le Hellard, S, Mather, KA, Milaneschi, Y, Morris, DW, Noethen, MM, Papiol, S, Rietschel, M, Santoro, ML, Steen, VM, Stein, JL, Streit, F, Tankard, RM, Teumer, A, van 't Ent, D, van der Meer, D, van Eijk, KR, Vassos, E, Vazquez-Bourgon, J, Witt, SH, Adams, HHH, Agartz, I, Ames, D, Amunts, K, Andreassen, OA, Arango, C, Banaschewski, T, Baune, BT, Belangero, SI, Bokde, ALW, Boomsma, DI, Bressan, RA, Brodaty, H, Buitelaar, JK, Cahn, W, Caspers, S, Cichon, S, Crespo-Facorro, B, Cox, SR, Dannlowski, U, Elvsashagen, T, Espeseth, T, Falkai, PG, Fisher, SE, Flor, H, Fullerton, JM, Garavan, H, Gowland, PA, Grabe, HJ, Hahn, T, Heinz, A, Hillegers, M, Hoare, J, Hoekstra, PJ, Ikram, MA, Jackowski, AP, Jansen, A, Jonsson, EG, Kahn, RS, Kircher, T, Korgaonkar, MS, Krug, A, Lemaitre, H, Malt, UF, Martinot, J-L, McDonald, C, Mitchell, PB, Muetzel, RL, Murray, RM, Nees, F, Nenadic, I, Oosterlaan, J, Ophoff, RA, Pan, PM, Penninx, BWJH, Poustka, L, Sachdev, PS, Salum, GA, Schofield, PR, Schumann, G, Shaw, P, Sim, K, Smolka, MN, Stein, DJ, Trollor, JN, van den Berg, LH, Veldink, JH, Walter, H, Westlye, LT, Whelan, R, White, T, Wright, MJ, Medland, SE, Franke, B, Thompson, PM, and Hulshoff Pol, HE
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Published: 2022

13. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, LM, Doucet, GE, Dima, D, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andreassen, OA, Anticevic, A, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, den Braber, A, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Calhoun, VD, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Chaim-Avancini, TM, Ching, CRK, Clark, VP, Conrod, PJ, Conzelmann, A, Crivello, F, Davey, CG, Dickie, EW, Ehrlich, S, Van't Ent, D, Fisher, SE, Fouche, J-P, Franke, B, Fuentes-Claramonte, P, de Geus, EJC, Di Giorgio, A, Glahn, DC, Gotlib, IH, Grabe, HJ, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Gurholt, TP, de Haan, L, Haatveit, B, Harrison, BJ, Hartman, CA, Hatton, SN, Heslenfeld, DJ, van den Heuvel, OA, Hickie, IB, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, AC, Jiang, J, Jonsson, EG, Joska, JA, Kalnin, AJ, Klein, M, Koenders, L, Kolskar, KK, Kramer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, IS, Lee, PH, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, BC, McDonald, C, McIntosh, AM, McMahon, KL, McPhilemy, G, van der Meer, D, Menchon, JM, Naaijen, J, Nyberg, L, Oosterlaan, J, Paloyelis, Y, Pauli, P, Pergola, G, Pomarol-Clotet, E, Portella, MJ, Radua, J, Reif, A, Richard, G, Roffman, JL, Rosa, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sarro, S, Satterthwaite, TD, Saykin, AJ, Serpa, MH, Sim, K, Simmons, A, Smoller, JW, Sommer, IE, Soriano-Mas, C, Stein, DJ, Strike, LT, Szeszko, PR, Temmingh, HS, Thomopoulos, S, Tomyshev, AS, Trollor, JN, Uhlmann, A, Veer, IM, Veltman, DJ, Voineskos, A, Volzke, H, Walter, H, Wang, L, Wang, Y, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, HC, Williams, SCR, Wittfeld, K, Wolf, DH, Wright, MJ, Yoncheva, YN, Zanetti, M, Ziegler, GC, de Zubicaray, G, Thompson, PM, Crone, EA, Frangou, S, Tamnes, CK, Wierenga, LM, Doucet, GE, Dima, D, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andreassen, OA, Anticevic, A, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, den Braber, A, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Calhoun, VD, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Chaim-Avancini, TM, Ching, CRK, Clark, VP, Conrod, PJ, Conzelmann, A, Crivello, F, Davey, CG, Dickie, EW, Ehrlich, S, Van't Ent, D, Fisher, SE, Fouche, J-P, Franke, B, Fuentes-Claramonte, P, de Geus, EJC, Di Giorgio, A, Glahn, DC, Gotlib, IH, Grabe, HJ, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Gurholt, TP, de Haan, L, Haatveit, B, Harrison, BJ, Hartman, CA, Hatton, SN, Heslenfeld, DJ, van den Heuvel, OA, Hickie, IB, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, AC, Jiang, J, Jonsson, EG, Joska, JA, Kalnin, AJ, Klein, M, Koenders, L, Kolskar, KK, Kramer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, IS, Lee, PH, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, BC, McDonald, C, McIntosh, AM, McMahon, KL, McPhilemy, G, van der Meer, D, Menchon, JM, Naaijen, J, Nyberg, L, Oosterlaan, J, Paloyelis, Y, Pauli, P, Pergola, G, Pomarol-Clotet, E, Portella, MJ, Radua, J, Reif, A, Richard, G, Roffman, JL, Rosa, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sarro, S, Satterthwaite, TD, Saykin, AJ, Serpa, MH, Sim, K, Simmons, A, Smoller, JW, Sommer, IE, Soriano-Mas, C, Stein, DJ, Strike, LT, Szeszko, PR, Temmingh, HS, Thomopoulos, S, Tomyshev, AS, Trollor, JN, Uhlmann, A, Veer, IM, Veltman, DJ, Voineskos, A, Volzke, H, Walter, H, Wang, L, Wang, Y, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, HC, Williams, SCR, Wittfeld, K, Wolf, DH, Wright, MJ, Yoncheva, YN, Zanetti, M, Ziegler, GC, de Zubicaray, G, Thompson, PM, Crone, EA, Frangou, S, and Tamnes, CK
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022

14. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author: Dima, D, Modabbernia, A, Papachristou, E, Doucet, GE, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Cervenka, S, Chaim-Avancini, TM, Ching, CRK, Chubar, V, Clark, VP, Conrod, P, Conzelmann, A, Crespo-Facorro, B, Crivello, F, Crone, EA, Dale, AM, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, Ortiz-Garcia De la Foz, V, Paloyelis, Y, Pauli, P, Pergola, G, Pomarol-Clotet, E, Portella, MJ, Potkin, SG, Radua, J, Reif, A, Rinker, DA, Roffman, JL, Rosa, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sanchez-Juan, P, Sarro, S, Satterthwaite, TD, Saykin, AJ, Serpa, MH, Schmaal, L, Schnell, K, Schumann, G, Sim, K, Smoller, JW, Sommer, I, Soriano-Mas, C, Stein, DJ, Strike, LT, Swagerman, SC, Tamnes, CK, Temmingh, HS, Thomopoulos, S, Tomyshev, AS, Tordesillas-Gutierrez, D, Trollor, JN, Turner, JA, Uhlmann, A, van den Heuvel, OA, van den Meer, D, van der Wee, NJA, van Haren, NEM, Van't Ent, D, van Erp, TGM, Veer, IM, Veltman, DJ, Voineskos, A, Voelzke, H, Walter, H, Walton, E, Wang, L, Wang, Y, Wassink, TH, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, H, Wierenga, LM, Williams, SCR, Wittfeld, K, Wolf, DH, Worker, A, Wright, MJ, Yang, K, Yoncheva, Y, Zanetti, M, Ziegler, GC, Thompson, PM, Frangou, S, Dima, D, Modabbernia, A, Papachristou, E, Doucet, GE, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Cervenka, S, Chaim-Avancini, TM, Ching, CRK, Chubar, V, Clark, VP, Conrod, P, Conzelmann, A, Crespo-Facorro, B, Crivello, F, Crone, EA, Dale, AM, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, Ortiz-Garcia De la Foz, V, Paloyelis, Y, Pauli, P, Pergola, G, Pomarol-Clotet, E, Portella, MJ, Potkin, SG, Radua, J, Reif, A, Rinker, DA, Roffman, JL, Rosa, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sanchez-Juan, P, Sarro, S, Satterthwaite, TD, Saykin, AJ, Serpa, MH, Schmaal, L, Schnell, K, Schumann, G, Sim, K, Smoller, JW, Sommer, I, Soriano-Mas, C, Stein, DJ, Strike, LT, Swagerman, SC, Tamnes, CK, Temmingh, HS, Thomopoulos, S, Tomyshev, AS, Tordesillas-Gutierrez, D, Trollor, JN, Turner, JA, Uhlmann, A, van den Heuvel, OA, van den Meer, D, van der Wee, NJA, van Haren, NEM, Van't Ent, D, van Erp, TGM, Veer, IM, Veltman, DJ, Voineskos, A, Voelzke, H, Walter, H, Walton, E, Wang, L, Wang, Y, Wassink, TH, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, H, Wierenga, LM, Williams, SCR, Wittfeld, K, Wolf, DH, Worker, A, Wright, MJ, Yang, K, Yoncheva, Y, Zanetti, M, Ziegler, GC, Thompson, PM, and Frangou, S
Abstract: Age 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.
Published: 2022

15. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Author: Frangou, S, Modabbernia, A, Williams, SCR, Papachristou, E, Doucet, GE, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Cervenka, S, Chaim-Avancini, TM, Ching, CRK, Chubar, V, Clark, VP, Conrod, P, Conzelmann, A, Crespo-Facorro, B, Crivello, F, Crone, EA, Dale, AM, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, de la Foz, VO-G, Paloyelis, Y, Pauli, P, Pergola, G, Pomarol-Clotet, E, Portella, MJ, Potkin, SG, Radua, J, Reif, A, Rinker, DA, Roffman, JL, Rosa, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sanchez-Juan, P, Sarro, S, Satterthwaite, TD, Saykin, AJ, Serpa, MH, Schmaal, L, Schnell, K, Schumann, G, Sim, K, Smoller, JW, Sommer, I, Soriano-Mas, C, Stein, DJ, Strike, LT, Swagerman, SC, Tamnes, CK, Temmingh, HS, Thomopoulos, S, Tomyshev, AS, Tordesillas-Gutierrez, D, Trollor, JN, Turner, JA, Uhlmann, A, van den Heuvel, OA, van den Meer, D, van der Wee, NJA, van Haren, NEM, van't Ent, D, van Erp, TGM, Veer, IM, Veltman, DJ, Voineskos, A, Voelzke, H, Walter, H, Walton, E, Wang, L, Wang, Y, Wassink, TH, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, H, Wierenga, LM, Wittfeld, K, Wolf, DH, Worker, A, Wright, MJ, Yang, K, Yoncheva, Y, Zanetti, M, Ziegler, GC, Thompson, PM, Dima, D, Frangou, S, Modabbernia, A, Williams, SCR, Papachristou, E, Doucet, GE, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Cervenka, S, Chaim-Avancini, TM, Ching, CRK, Chubar, V, Clark, VP, Conrod, P, Conzelmann, A, Crespo-Facorro, B, Crivello, F, Crone, EA, Dale, AM, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, de la Foz, VO-G, Paloyelis, Y, Pauli, P, Pergola, G, Pomarol-Clotet, E, Portella, MJ, Potkin, SG, Radua, J, Reif, A, Rinker, DA, Roffman, JL, Rosa, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sanchez-Juan, P, Sarro, S, Satterthwaite, TD, Saykin, AJ, Serpa, MH, Schmaal, L, Schnell, K, Schumann, G, Sim, K, Smoller, JW, Sommer, I, Soriano-Mas, C, Stein, DJ, Strike, LT, Swagerman, SC, Tamnes, CK, Temmingh, HS, Thomopoulos, S, Tomyshev, AS, Tordesillas-Gutierrez, D, Trollor, JN, Turner, JA, Uhlmann, A, van den Heuvel, OA, van den Meer, D, van der Wee, NJA, van Haren, NEM, van't Ent, D, van Erp, TGM, Veer, IM, Veltman, DJ, Voineskos, A, Voelzke, H, Walter, H, Walton, E, Wang, L, Wang, Y, Wassink, TH, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, H, Wierenga, LM, Wittfeld, K, Wolf, DH, Worker, A, Wright, MJ, Yang, K, Yoncheva, Y, Zanetti, M, Ziegler, GC, Thompson, PM, and Dima, D
Abstract: Delineating 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.
Published: 2022

16. Deep Generative Medical Image Harmonization for Improving Cross-Site Generalization in Deep Learning Predictors

Author: Bashyam, VM, Doshi, J, Erus, G, Srinivasan, D, Abdulkadir, A, Singh, A, Habes, M, Fan, Y, Masters, CL, Maruff, P, Zhuo, C, Voelzke, H, Johnson, SC, Fripp, J, Koutsouleris, N, Satterthwaite, TD, Wolf, DH, Gur, RE, Gur, RC, Morris, JC, Albert, MS, Grabe, HJ, Resnick, SM, Bryan, NR, Wittfeld, K, Bulow, R, Wolk, DA, Shou, H, Nasrallah, IM, Davatzikos, C, Bashyam, VM, Doshi, J, Erus, G, Srinivasan, D, Abdulkadir, A, Singh, A, Habes, M, Fan, Y, Masters, CL, Maruff, P, Zhuo, C, Voelzke, H, Johnson, SC, Fripp, J, Koutsouleris, N, Satterthwaite, TD, Wolf, DH, Gur, RE, Gur, RC, Morris, JC, Albert, MS, Grabe, HJ, Resnick, SM, Bryan, NR, Wittfeld, K, Bulow, R, Wolk, DA, Shou, H, Nasrallah, IM, and Davatzikos, C
Abstract: BACKGROUND: In the medical imaging domain, deep learning-based methods have yet to see widespread clinical adoption, in part due to limited generalization performance across different imaging devices and acquisition protocols. The deviation between estimated brain age and biological age is an established biomarker of brain health and such models may benefit from increased cross-site generalizability. PURPOSE: To develop and evaluate a deep learning-based image harmonization method to improve cross-site generalizability of deep learning age prediction. STUDY TYPE: Retrospective. POPULATION: Eight thousand eight hundred and seventy-six subjects from six sites. Harmonization models were trained using all subjects. Age prediction models were trained using 2739 subjects from a single site and tested using the remaining 6137 subjects from various other sites. FIELD STRENGTH/SEQUENCE: Brain imaging with magnetization prepared rapid acquisition with gradient echo or spoiled gradient echo sequences at 1.5 T and 3 T. ASSESSMENT: StarGAN v2, was used to perform a canonical mapping from diverse datasets to a reference domain to reduce site-based variation while preserving semantic information. Generalization performance of deep learning age prediction was evaluated using harmonized, histogram matched, and unharmonized data. STATISTICAL TESTS: Mean absolute error (MAE) and Pearson correlation between estimated age and biological age quantified the performance of the age prediction model. RESULTS: Our results indicated a substantial improvement in age prediction in out-of-sample data, with the overall MAE improving from 15.81 (±0.21) years to 11.86 (±0.11) with histogram matching to 7.21 (±0.22) years with generative adversarial network (GAN)-based harmonization. In the multisite case, across the 5 out-of-sample sites, MAE improved from 9.78 (±6.69) years to 7.74 (±3.03) years with histogram normalization to 5.32 (±4.07) years with GAN-based harmonization. DATA CONCLUSION: While
Published: 2022

17. Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group

Author: Ho, TC, Gutman, B, Pozzi, E, Grabe, HJ, Hosten, N, Wittfeld, K, Voelzke, H, Baune, B, Dannlowski, U, Foerster, K, Grotegerd, D, Redlich, R, Jansen, A, Kircher, T, Krug, A, Meinert, S, Nenadic, I, Opel, N, Dinga, R, Veltman, DJ, Schnell, K, Veer, I, Walter, H, Gotlib, IH, Sacchet, MD, Aleman, A, Groenewold, NA, Stein, DJ, Li, M, Walter, M, Ching, CRK, Jahanshad, N, Ragothaman, A, Isaev, D, Zavaliangos-Petropulu, A, Thompson, PM, Saemann, PG, Schmaal, L, Ho, TC, Gutman, B, Pozzi, E, Grabe, HJ, Hosten, N, Wittfeld, K, Voelzke, H, Baune, B, Dannlowski, U, Foerster, K, Grotegerd, D, Redlich, R, Jansen, A, Kircher, T, Krug, A, Meinert, S, Nenadic, I, Opel, N, Dinga, R, Veltman, DJ, Schnell, K, Veer, I, Walter, H, Gotlib, IH, Sacchet, MD, Aleman, A, Groenewold, NA, Stein, DJ, Li, M, Walter, M, Ching, CRK, Jahanshad, N, Ragothaman, A, Isaev, D, Zavaliangos-Petropulu, A, Thompson, PM, Saemann, PG, and Schmaal, L
Abstract: Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = -0.164 to -0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = -0.173 to -0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.
Published: 2022

18. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author: Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., Räikkönen, K., Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., and Räikkönen, K.
Abstract: Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
Published: 2022

19. The Role of Educational Attainment and Brain Morphology in Major Depressive Disorder: Findings From the ENIGMA Major Depressive Disorder Consortium

Author: Whittle, S, Rakesh, D, Schmaal, L, Veltman, DJ, Thompson, PM, Singh, A, Gonul, AS, Aleman, A, Demir, AU, Krug, A, Mwangi, B, Kramer, B, Baune, BT, Stein, DJ, Grotegerd, D, Pomarol-Clotet, E, Rodriguez-Cano, E, Melloni, E, Benedetti, F, Stein, F, Grabe, HJ, Volzke, H, Gotlib, IH, Nenadic, I, Soares, JC, Repple, J, Sim, K, Brosch, K, Wittfeld, K, Berger, K, Hermesdorf, M, Portella, MJ, Sacchet, MD, Wu, M-J, Opel, N, Groenewold, NA, Gruber, O, Fuentes-Claramonte, P, Salvador, R, Goya-Maldonado, R, Sarro, S, Poletti, S, Meinert, SL, Kircher, T, Dannlowski, U, Pozzi, E, Whittle, S, Rakesh, D, Schmaal, L, Veltman, DJ, Thompson, PM, Singh, A, Gonul, AS, Aleman, A, Demir, AU, Krug, A, Mwangi, B, Kramer, B, Baune, BT, Stein, DJ, Grotegerd, D, Pomarol-Clotet, E, Rodriguez-Cano, E, Melloni, E, Benedetti, F, Stein, F, Grabe, HJ, Volzke, H, Gotlib, IH, Nenadic, I, Soares, JC, Repple, J, Sim, K, Brosch, K, Wittfeld, K, Berger, K, Hermesdorf, M, Portella, MJ, Sacchet, MD, Wu, M-J, Opel, N, Groenewold, NA, Gruber, O, Fuentes-Claramonte, P, Salvador, R, Goya-Maldonado, R, Sarro, S, Poletti, S, Meinert, SL, Kircher, T, Dannlowski, U, and Pozzi, E
Abstract: Brain structural abnormalities and low educational attainment are consistently associated with major depressive disorder (MDD), yet there has been little research investigating the complex interaction of these factors. Brain structural alterations may represent a vulnerability or differential susceptibility marker, and in the context of low educational attainment, predict MDD. We tested this moderation model in a large multisite sample of 1958 adults with MDD and 2921 controls (aged 18 to 86) from the ENIGMA MDD working group. Using generalized linear mixed models and within-sample split-half replication, we tested whether brain structure interacted with educational attainment to predict MDD status. Analyses revealed that cortical thickness in a number of occipital, parietal, and frontal regions significantly interacted with education to predict MDD. For the majority of regions, models suggested a differential susceptibility effect, whereby thicker cortex was more likely to predict MDD in individuals with low educational attainment, but less likely to predict MDD in individuals with high educational attainment. Findings suggest that greater thickness of brain regions subserving visuomotor and social-cognitive functions confers susceptibility to MDD, dependent on level of educational attainment. Longitudinal work, however, is ultimately needed to establish whether cortical thickness represents a preexisting susceptibility marker. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Published: 2022

20. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author: Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, Raikkonen, K, Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, and Raikkonen, K
Abstract: Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
Published: 2022

21. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author: Patel, Y, Shin, J, Abe, C, Agartz, I, Alloza, C, Alnaes, D, Ambrogi, S, Antonucci, LA, Arango, C, Arolt, V, Auzias, G, Ayesa-Arriola, R, Banaj, N, Banaschewski, T, Bandeira, C, Basgoze, Z, Cupertino, RB, Bau, CHD, Bauer, J, Baumeister, S, Bernardoni, F, Bertolino, A, del Mar Bonnin, C, Brandeis, D, Brem, S, Bruggemann, J, Bulow, R, Bustillo, JR, Calderoni, S, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carmona, S, Carr, VJ, Catts, SV, Chenji, S, Chew, QH, Coghill, D, Connolly, CG, Conzelmann, A, Craven, AR, Crespo-Facorro, B, Cullen, K, Dahl, A, Dannlowski, U, Davey, CG, Deruelle, C, Diaz-Caneja, CM, Dohm, K, Ehrlich, S, Epstein, J, Erwin-Grabner, T, Eyler, LT, Fedor, J, Fitzgerald, J, Foran, W, Ford, JM, Fortea, L, Fuentes-Claramonte, P, Fullerton, J, Furlong, L, Gallagher, L, Gao, B, Gao, S, Goikolea, JM, Gotlib, I, Goya-Maldonado, R, Grabe, HJ, Green, M, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Haavik, J, Hahn, T, Harrison, BJ, Heindel, W, Henskens, F, Heslenfeld, DJ, Hilland, E, Hoekstra, PJ, Hohmann, S, Holz, N, Howells, FM, Ipser, JC, Jahanshad, N, Jakobi, B, Jansen, A, Janssen, J, Jonassen, R, Kaiser, A, Kaleda, V, Karantonis, J, King, JA, Kircher, T, Kochunov, P, Koopowitz, S-M, Landen, M, Landro, NI, Lawrie, S, Lebedeva, I, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Mathalon, DH, McDonald, C, McIntosh, A, Meinert, S, Michie, PT, Mitchell, P, Moreno-Alcazar, A, Mowry, B, Muratori, F, Nabulsi, L, Nenadic, I, Tuura, RO, Oosterlaan, J, Overs, B, Pantelis, C, Parellada, M, Pariente, JC, Pauli, P, Pergola, G, Piarulli, FM, Picon, F, Piras, F, Pomarol-Clotet, E, Pretus, C, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Reif, A, Retico, A, Roberts, G, Rossell, S, Rovaris, DL, Rubia, K, Sacchet, M, Salavert, J, Salvador, R, Sarro, S, Sawa, A, Schall, U, Scott, R, Selvaggi, P, Silk, T, Sim, K, Skoch, A, Spalletta, G, Spaniel, F, Stein, DJ, Steinstrater, O, Stolicyn, A, Takayanagi, Y, Tamm, L, Tavares, M, Teumer, A, Thiel, K, Thomopoulos, SI, Tomecek, D, Tomyshev, AS, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, Van Rheenen, T, Vazquez-Bourgon, J, Vernooij, MW, Vieta, E, Vilarroya, O, Weickert, C, Weickert, T, Westlye, LT, Whalley, H, Willinger, D, Winter, A, Wittfeld, K, Yang, TT, Yoncheva, Y, Zijlmans, JL, Hoogman, M, Franke, B, van Rooij, D, Buitelaar, J, Ching, CRK, Andreassen, OA, Pozzi, E, Veltman, D, Schmaal, L, van Erp, TGM, Turner, J, Castellanos, FX, Pausova, Z, Thompson, P, Paus, T, Patel, Y, Shin, J, Abe, C, Agartz, I, Alloza, C, Alnaes, D, Ambrogi, S, Antonucci, LA, Arango, C, Arolt, V, Auzias, G, Ayesa-Arriola, R, Banaj, N, Banaschewski, T, Bandeira, C, Basgoze, Z, Cupertino, RB, Bau, CHD, Bauer, J, Baumeister, S, Bernardoni, F, Bertolino, A, del Mar Bonnin, C, Brandeis, D, Brem, S, Bruggemann, J, Bulow, R, Bustillo, JR, Calderoni, S, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carmona, S, Carr, VJ, Catts, SV, Chenji, S, Chew, QH, Coghill, D, Connolly, CG, Conzelmann, A, Craven, AR, Crespo-Facorro, B, Cullen, K, Dahl, A, Dannlowski, U, Davey, CG, Deruelle, C, Diaz-Caneja, CM, Dohm, K, Ehrlich, S, Epstein, J, Erwin-Grabner, T, Eyler, LT, Fedor, J, Fitzgerald, J, Foran, W, Ford, JM, Fortea, L, Fuentes-Claramonte, P, Fullerton, J, Furlong, L, Gallagher, L, Gao, B, Gao, S, Goikolea, JM, Gotlib, I, Goya-Maldonado, R, Grabe, HJ, Green, M, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Haavik, J, Hahn, T, Harrison, BJ, Heindel, W, Henskens, F, Heslenfeld, DJ, Hilland, E, Hoekstra, PJ, Hohmann, S, Holz, N, Howells, FM, Ipser, JC, Jahanshad, N, Jakobi, B, Jansen, A, Janssen, J, Jonassen, R, Kaiser, A, Kaleda, V, Karantonis, J, King, JA, Kircher, T, Kochunov, P, Koopowitz, S-M, Landen, M, Landro, NI, Lawrie, S, Lebedeva, I, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Mathalon, DH, McDonald, C, McIntosh, A, Meinert, S, Michie, PT, Mitchell, P, Moreno-Alcazar, A, Mowry, B, Muratori, F, Nabulsi, L, Nenadic, I, Tuura, RO, Oosterlaan, J, Overs, B, Pantelis, C, Parellada, M, Pariente, JC, Pauli, P, Pergola, G, Piarulli, FM, Picon, F, Piras, F, Pomarol-Clotet, E, Pretus, C, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Reif, A, Retico, A, Roberts, G, Rossell, S, Rovaris, DL, Rubia, K, Sacchet, M, Salavert, J, Salvador, R, Sarro, S, Sawa, A, Schall, U, Scott, R, Selvaggi, P, Silk, T, Sim, K, Skoch, A, Spalletta, G, Spaniel, F, Stein, DJ, Steinstrater, O, Stolicyn, A, Takayanagi, Y, Tamm, L, Tavares, M, Teumer, A, Thiel, K, Thomopoulos, SI, Tomecek, D, Tomyshev, AS, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, Van Rheenen, T, Vazquez-Bourgon, J, Vernooij, MW, Vieta, E, Vilarroya, O, Weickert, C, Weickert, T, Westlye, LT, Whalley, H, Willinger, D, Winter, A, Wittfeld, K, Yang, TT, Yoncheva, Y, Zijlmans, JL, Hoogman, M, Franke, B, van Rooij, D, Buitelaar, J, Ching, CRK, Andreassen, OA, Pozzi, E, Veltman, D, Schmaal, L, van Erp, TGM, Turner, J, Castellanos, FX, Pausova, Z, Thompson, P, and Paus, T
Abstract: BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t
Published: 2022

22. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author: Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L.A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R.B., Bau, C.H.D., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C.D.M., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J.R., Calderoni, S., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carmona, S., Carr, V.J., Catts, S.V., Chenji, S., Chew, Q.H., Coghill, D., Connolly, C.G., Conzelmann, A., Craven, A.R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C.G., Deruelle, C., Díaz-Caneja, C.M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L.T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J.M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J.M., Gotlib, I., Goya-Maldonado, R., Grabe, H.J., Green, M., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B.J., Heindel, W., Henskens, F., Heslenfeld, D.J., Hilland, E., Hoekstra, P.J., Hohmann, S., Holz, N., Howells, F.M., Ipser, J.C., Jahanshad, N., Jakobi, B., Jansen, A., Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J.A., Kircher, T., Kochunov, P., Koopowitz, S.-M., Landén, M., Landrø, N.I., Lawrie, S., Lebedeva, I., Luna, B., Lundervold, A.J., MacMaster, F.P., Maglanoc, L.A., Mathalon, D.H., McDonald, C., McIntosh, A., Meinert, S., Michie, P.T., Mitchell, P., Moreno-Alcázar, A., Mowry, B., Muratori, F., Nabulsi, L., Nenadić, I., O'Gorman Tuura, R., Oosterlaan, J., Overs, B., Pantelis, C., Parellada, M., Pariente, J.C., Pauli, P., Pergola, G., Piarulli, F.M., Picon, F., Piras, F., Pomarol-Clotet, E., Pretus, C., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Reif, A., Retico, A., Roberts, G., Rossell, S., Rovaris, D.L., Rubia, K., Sacchet, M., Salavert, J., Salvador, R., Sarró, S., Sawa, A., Schall, U., Scott, R., Selvaggi, P., Silk, T., Sim, K., Skoch, A., Spalletta, G., Spaniel, F., Stein, D.J., Steinsträter, O., Stolicyn, A., Takayanagi, Y., Tamm, L., Tavares, M., Teumer, A., Thiel, K., Thomopoulos, S.I., Tomecek, D., Tomyshev, A.S., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Rheenen, T., Vazquez-Bourgón, J., Vernooij, M.W., Vieta, E., Vilarroya, O., Weickert, C., Weickert, T., Westlye, L.T., Whalley, H., Willinger, D., Winter, A., Wittfeld, K., Yang, T.T., Yoncheva, Y., Zijlmans, J.L., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J., Ching, C.R.K., Andreassen, O.A., Pozzi, E., Veltman, D., Schmaal, L., van Erp, T.G.M., Turner, J., Castellanos, F.X., Pausova, Z., Thompson, P., Paus, T., Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L.A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R.B., Bau, C.H.D., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C.D.M., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J.R., Calderoni, S., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carmona, S., Carr, V.J., Catts, S.V., Chenji, S., Chew, Q.H., Coghill, D., Connolly, C.G., Conzelmann, A., Craven, A.R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C.G., Deruelle, C., Díaz-Caneja, C.M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L.T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J.M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J.M., Gotlib, I., Goya-Maldonado, R., Grabe, H.J., Green, M., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B.J., Heindel, W., Henskens, F., Heslenfeld, D.J., Hilland, E., Hoekstra, P.J., Hohmann, S., Holz, N., Howells, F.M., Ipser, J.C., Jahanshad, N., Jakobi, B., Jansen, A., Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J.A., Kircher, T., Kochunov, P., Koopowitz, S.-M., Landén, M., Landrø, N.I., Lawrie, S., Lebedeva, I., Luna, B., Lundervold, A.J., MacMaster, F.P., Maglanoc, L.A., Mathalon, D.H., McDonald, C., McIntosh, A., Meinert, S., Michie, P.T., Mitchell, P., Moreno-Alcázar, A., Mowry, B., Muratori, F., Nabulsi, L., Nenadić, I., O'Gorman Tuura, R., Oosterlaan, J., Overs, B., Pantelis, C., Parellada, M., Pariente, J.C., Pauli, P., Pergola, G., Piarulli, F.M., Picon, F., Piras, F., Pomarol-Clotet, E., Pretus, C., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Reif, A., Retico, A., Roberts, G., Rossell, S., Rovaris, D.L., Rubia, K., Sacchet, M., Salavert, J., Salvador, R., Sarró, S., Sawa, A., Schall, U., Scott, R., Selvaggi, P., Silk, T., Sim, K., Skoch, A., Spalletta, G., Spaniel, F., Stein, D.J., Steinsträter, O., Stolicyn, A., Takayanagi, Y., Tamm, L., Tavares, M., Teumer, A., Thiel, K., Thomopoulos, S.I., Tomecek, D., Tomyshev, A.S., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Rheenen, T., Vazquez-Bourgón, J., Vernooij, M.W., Vieta, E., Vilarroya, O., Weickert, C., Weickert, T., Westlye, L.T., Whalley, H., Willinger, D., Winter, A., Wittfeld, K., Yang, T.T., Yoncheva, Y., Zijlmans, J.L., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J., Ching, C.R.K., Andreassen, O.A., Pozzi, E., Veltman, D., Schmaal, L., van Erp, T.G.M., Turner, J., Castellanos, F.X., Pausova, Z., Thompson, P., and Paus, T.
Abstract: Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t
Published: 2022
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23. Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure

Author: Dannlowski, U, Grabe, H J, Wittfeld, K, Klaus, J, Konrad, C, Grotegerd, D, Redlich, R, Suslow, T, Opel, N, Ohrmann, P, Bauer, J, Zwanzger, P, Laeger, I, Hohoff, C, Arolt, V, Heindel, W, Deppe, M, Domschke, K, Hegenscheid, K, Völzke, H, Stacey, D, Meyer zu Schwabedissen, H, Kugel, H, and Baune, B T
Published: 2015
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24. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Author: Sønderby, I.E., Ching, CRK, Thomopoulos, S.I., van der Meer, D., Sun, D., Villalon-Reina, J.E., Agartz, I., Amunts, K., Arango, C., Armstrong, N.J., Ayesa-Arriola, R., Bakker, G., Bassett, A.S., Boomsma, D.I., Bülow, R., Butcher, N.J., Calhoun, V.D., Caspers, S., Chow, EWC, Cichon, S., Ciufolini, S., Craig, M.C., Crespo-Facorro, B., Cunningham, A.C., Dale, A.M., Dazzan, P., de Zubicaray, G.I., Djurovic, S., Doherty, J.L., Donohoe, G., Draganski, B., Durdle, C.A., Ehrlich, S., Emanuel, B.S., Espeseth, T., Fisher, S.E., Ge, T., Glahn, D.C., Grabe, H.J., Gur, R.E., Gutman, B.A., Haavik, J., Håberg, A.K., Hansen, L.A., Hashimoto, R., Hibar, D.P., Holmes, A.J., Hottenga, J.J., Hulshoff Pol, H.E., Jalbrzikowski, M., Knowles, EEM, Kushan, L., Linden, DEJ, Liu, J., Lundervold, A.J., Martin-Brevet, S., Martínez, K., Mather, K.A., Mathias, S.R., McDonald-McGinn, D.M., McRae, A.F., Medland, S.E., Moberget, T., Modenato, C., Monereo Sánchez, J., Moreau, C.A., Mühleisen, T.W., Paus, T., Pausova, Z., Prieto, C., Ragothaman, A., Reinbold, C.S., Reis Marques, T., Repetto, G.M., Reymond, A., Roalf, D.R., Rodriguez-Herreros, B., Rucker, J.J., Sachdev, P.S., Schmitt, J.E., Schofield, P.R., Silva, A.I., Stefansson, H., Stein, D.J., Tamnes, C.K., Tordesillas-Gutiérrez, D., Ulfarsson, M.O., Vajdi, A., van 't Ent, D., van den Bree, MBM, Vassos, E., Vázquez-Bourgon, J., Vila-Rodriguez, F., Walters, G.B., Wen, W., Westlye, L.T., Wittfeld, K., Zackai, E.H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Bearden, C.E., Andreassen, O.A., ENIGMA-CNV Working Group, ENIGMA 22q11.2 Deletion Syndrome Working Group, Bernard, M., Blackburn, N.B., Bøen, R., de Geus, E., de Zwarte, SMC, Forti, M.D., Frei, O., Fukunaga, M., Hehir-Kwa, J.Y., Hillegers, MHJ, Hoffmann, P., Homuth, G., Jahanshad, N., Koops, S., Kumar, K., Kikuchi, M., Le Hellard, S., Leu, C., Murray, R.M., Naerland, T., Nyberg, L., Ophoff, R.A., Pike, G.B., Sando, S.B., Shin, J., Shumskaya, E., Sisodiya, S.M., Steen, V.M., Teumer, A., Uhlmann, A., Wright, M.J., Antshel, K.M., Campbell, L.E., Crossley, N.A., Crowley, T.B., Daly, E., Fiksinski, A.M., Forsyth, J.K., Fremont, W., Goodrich-Hunsaker, N.J., Gudbrandsen, M., Jonas, R.K., Kates, W.R., Lin, A., McCabe, K.L., Moss, H., Murphy, D.G., Murphy, K.C., Owen, M.J., Ruparel, K., Simon, T.J., van Amelsvoort, T., and Vorstman, JAS
Subjects: brain structural imaging, copy number variant, diffusion tensor imaging, evolution, genetics-first approach, neurodevelopmental disorders, psychiatric disorders
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Published: 2022

25. Moderating effects of serum vitamin D on brain structure

Author: Bonk, S, Terock, J, Van der Auwera, S, Frenzel, S, Wittfeld, K, Hosten, N, Nauck, M, Völzke, H, and Grabe, H
Subjects: ddc: 610, 610 Medical sciences, Medicine
Abstract: Background: Vitamin D deficiency is common in the German population and is known to affect a wide range of pathways in human metabolism. As an example, previous studies found a link between Alzheimer's disease and modifications of brain structures [ref:1], [ref:2]. Motivated[for full text, please go to the a.m. URL], 65th Annual Meeting of the German Association for Medical Informatics, Biometry and Epidemiology (GMDS), Meeting of the Central European Network (CEN: German Region, Austro-Swiss Region and Polish Region) of the International Biometric Society (IBS)
Published: 2021
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26. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author: Han, L.K.M., Dinga, R., Hahn, T., Ching, C.R., Eyler, L.T., Aftanas, L., Aghajani, M., Aleman, A., Baune, B.T., Berger, K., Brak, I., Filho, G.B., Carballedo, A., Connolly, C.G., Couvy-Duchesne, B., Cullen, K.R., Dannlowski, U., Davey, C.G., Dima, D., Duran, F.L.S., Enneking, V., Filimonova, E., Frenzel, S., Frodl, T., Fu, C.H.Y., Godlewska, B.R., Gotlib, I.H., Grabe, H.J., Groenewold, N.A., Grotegerd, D., Gruber, O., Hall, G.B., Harrison, B.J., Hatton, S.N., Hermesdorf, M., Hickie, I.B., Ho, T.C., Hosten, N., Jansen, Andreas, Kähler, C., Kircher, T., Klimes-Dougan, B., Krämer, B., Krug, A., Lagopoulos, J., Leenings, R., MacMaster, F.P., MacQueen, G., McIntosh, A., McLellan, Q., McMahon, K.L., Medland, S.E., Mueller, B.A., Mwangi, B., Osipov, E., Portella, M.J., Pozzi, E., Reneman, L., Repple, J., Rosa, P.G., Sacchet, M.D., Sämann, P.G., Schnell, K., Schrantee, A., Simulionyte, E., Soares, J.C., Sommer, J., Stein, D.J., Steinsträter, O., Strike, L.T., Thomopoulos, S.I., Tol, M.J.D. van, Veer, I.M., Vermeiren, R., Walter, H., Wee, N.J.A. van der, Werff, S.J.A. van der, Whalley, H., Winter, N.R., Wittfeld, K., Wright, M.J., Wu, M.J., Völzke, H., Yang, T.T., Zannias, V., Zubicaray, G.I. de, Zunta-Soares, G.B., Abé, C., Alda, M., Andreassen, O.A., Bøen, E., Bonnin, C.M., Canales-Rodriguez, E.J., Cannon, D., Caseras, X., Chaim-Avancini, T.M., Elvsåshagen, T., Favre, P., Foley, S.F., Fullerton, J.M., Ruhé, H.G., Schene, A.H., Marquand, A.F., Cole, J., Schmaal, L., Han, L.K.M., Dinga, R., Hahn, T., Ching, C.R., Eyler, L.T., Aftanas, L., Aghajani, M., Aleman, A., Baune, B.T., Berger, K., Brak, I., Filho, G.B., Carballedo, A., Connolly, C.G., Couvy-Duchesne, B., Cullen, K.R., Dannlowski, U., Davey, C.G., Dima, D., Duran, F.L.S., Enneking, V., Filimonova, E., Frenzel, S., Frodl, T., Fu, C.H.Y., Godlewska, B.R., Gotlib, I.H., Grabe, H.J., Groenewold, N.A., Grotegerd, D., Gruber, O., Hall, G.B., Harrison, B.J., Hatton, S.N., Hermesdorf, M., Hickie, I.B., Ho, T.C., Hosten, N., Jansen, Andreas, Kähler, C., Kircher, T., Klimes-Dougan, B., Krämer, B., Krug, A., Lagopoulos, J., Leenings, R., MacMaster, F.P., MacQueen, G., McIntosh, A., McLellan, Q., McMahon, K.L., Medland, S.E., Mueller, B.A., Mwangi, B., Osipov, E., Portella, M.J., Pozzi, E., Reneman, L., Repple, J., Rosa, P.G., Sacchet, M.D., Sämann, P.G., Schnell, K., Schrantee, A., Simulionyte, E., Soares, J.C., Sommer, J., Stein, D.J., Steinsträter, O., Strike, L.T., Thomopoulos, S.I., Tol, M.J.D. van, Veer, I.M., Vermeiren, R., Walter, H., Wee, N.J.A. van der, Werff, S.J.A. van der, Whalley, H., Winter, N.R., Wittfeld, K., Wright, M.J., Wu, M.J., Völzke, H., Yang, T.T., Zannias, V., Zubicaray, G.I. de, Zunta-Soares, G.B., Abé, C., Alda, M., Andreassen, O.A., Bøen, E., Bonnin, C.M., Canales-Rodriguez, E.J., Cannon, D., Caseras, X., Chaim-Avancini, T.M., Elvsåshagen, T., Favre, P., Foley, S.F., Fullerton, J.M., Ruhé, H.G., Schene, A.H., Marquand, A.F., Cole, J., and Schmaal, L.
Abstract: Item does not contain fulltext, Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
Published: 2021

27. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author: Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Andreassen, O.A., Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., and Andreassen, O.A.
Abstract: Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
Published: 2021

28. Effects of copy number variations on brain structure and risk for psychiatric illness: Large‐scale studies from the ENIGMA working groups on CNVs

Author: Sønderby, I.E., Ching, C.R.K., Thomopoulos, S.I., Meer, D., Sun, D., Villalon‐Reina, J.E., Agartz, I., Amunts, K., Arango, C., Armstrong, N.J., Ayesa‐Arriola, R., Bakker, G., Bassett, A.S., Boomsma, D.I., Bülow, R., Butcher, N.J., Calhoun, V.D., Caspers, S., Chow, E.W.C., Cichon, S., Ciufolini, S., Craig, M.C., Crespo‐Facorro, B., Cunningham, A.C., Dale, A.M., Dazzan, P., Zubicaray, G.I., Djurovic, S., Doherty, J.L., Donohoe, G., Draganski, B., Durdle, C.A., Ehrlich, S., Emanuel, B.S., Espeseth, T., Fisher, S.E., Ge, T., Glahn, D.C., Grabe, H.J., Gur, R.E., Gutman, B.A., Haavik, J., Håberg, A.K., Hansen, L.A., Hashimoto, R., Hibar, D.P., Holmes, A.J., Hottenga, J‐J, Hulshoff Pol, H.E., Jalbrzikowski, M., Knowles, E.E.M., Kushan, L., Linden, D.E.J., Liu, J., Lundervold, A.J., Martin‐Brevet, S., Martinez, K., Mather, K.A., Mathias, S.R., McDonald‐McGinn, D.M., McRae, A.F., Medland, S.E., Moberget, T., Modenato, C., Monereo Sánchez, J., Moreau, C.A., Mühleisen, T.W., Paus, T., Pausova, Z., Prieto, C., Ragothaman, A., Reinbold, C.S., Reis Marques, T., Repetto, G.M., Reymond, A., Roalf, D.R., Rodriguez‐Herreros, B., Rucker, J.J., Sachdev, P.S., Schmitt, J.E., Schofield, P.R., Silva, A.I., Stefánsson, H., Stein, D.J., Tamnes, C.K., Tordesillas‐Gutiérrez, D., Ulfarsson, M.O., Vajdi, A., Ent, D., Bree, M.B.M., Vassos, E., Vázquez‐Bourgon, J., Vila‐Rodriguez, F., Walters, G.B., Wen, W., Westlye, L.T., Wittfeld, K., Zackai, E.H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Bearden, C.E., Andreassen, O.A., Sønderby, I.E., Ching, C.R.K., Thomopoulos, S.I., Meer, D., Sun, D., Villalon‐Reina, J.E., Agartz, I., Amunts, K., Arango, C., Armstrong, N.J., Ayesa‐Arriola, R., Bakker, G., Bassett, A.S., Boomsma, D.I., Bülow, R., Butcher, N.J., Calhoun, V.D., Caspers, S., Chow, E.W.C., Cichon, S., Ciufolini, S., Craig, M.C., Crespo‐Facorro, B., Cunningham, A.C., Dale, A.M., Dazzan, P., Zubicaray, G.I., Djurovic, S., Doherty, J.L., Donohoe, G., Draganski, B., Durdle, C.A., Ehrlich, S., Emanuel, B.S., Espeseth, T., Fisher, S.E., Ge, T., Glahn, D.C., Grabe, H.J., Gur, R.E., Gutman, B.A., Haavik, J., Håberg, A.K., Hansen, L.A., Hashimoto, R., Hibar, D.P., Holmes, A.J., Hottenga, J‐J, Hulshoff Pol, H.E., Jalbrzikowski, M., Knowles, E.E.M., Kushan, L., Linden, D.E.J., Liu, J., Lundervold, A.J., Martin‐Brevet, S., Martinez, K., Mather, K.A., Mathias, S.R., McDonald‐McGinn, D.M., McRae, A.F., Medland, S.E., Moberget, T., Modenato, C., Monereo Sánchez, J., Moreau, C.A., Mühleisen, T.W., Paus, T., Pausova, Z., Prieto, C., Ragothaman, A., Reinbold, C.S., Reis Marques, T., Repetto, G.M., Reymond, A., Roalf, D.R., Rodriguez‐Herreros, B., Rucker, J.J., Sachdev, P.S., Schmitt, J.E., Schofield, P.R., Silva, A.I., Stefánsson, H., Stein, D.J., Tamnes, C.K., Tordesillas‐Gutiérrez, D., Ulfarsson, M.O., Vajdi, A., Ent, D., Bree, M.B.M., Vassos, E., Vázquez‐Bourgon, J., Vila‐Rodriguez, F., Walters, G.B., Wen, W., Westlye, L.T., Wittfeld, K., Zackai, E.H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Bearden, C.E., and Andreassen, O.A.
Abstract: The Enhancing NeuroImaging Genetics through Meta‐Analysis copy number variant (ENIGMA‐CNV) and 22q11.2 Deletion Syndrome Working Groups (22q‐ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA‐CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q‐ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest‐ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi‐site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene‐dosage effects on distinct brain regions also emerged, providing further insight into genotype–phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype‐first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Published: 2021

29. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Author: Frangou, S. (Sophia), Modabbernia, A. (Amirhossein), Williams, S.C.R. (Steven C. R.), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L. (Lisa), Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), Ent, D. (Dennis) van 't, Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), Dima, D. (Danai), Frangou, S. (Sophia), Modabbernia, A. (Amirhossein), Williams, S.C.R. (Steven C. R.), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L. (Lisa), Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), Ent, D. (Dennis) van 't, Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), and Dima, D. (Danai)
Abstract: Delineating 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.
Published: 2021
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30. Brain Correlates of Suicide Attempt in 18,925 Participants Across 18 International Cohorts

Author: Campos, A, Thompson, PM, Veltman, DJ, Pozzi, E, van Veltzen, LS, Jahanshad, N, Adams, MJ, Baune, BT, Berger, K, Brosch, K, Bulow, R, Connolly, CG, Dannlowski, U, Davey, CG, de Zubicaray, G, Dima, D, Erwin-Grabner, T, Evans, JW, Fu, CHY, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Grotegerd, D, Harris, MA, Harrison, BJ, Hatton, SN, Hermesdorf, M, Hickie, IB, Ho, TC, Kircher, T, Krug, A, Lagopoulos, J, Lemke, H, McMahon, K, MacMaster, FP, Martin, NG, McIntosh, AM, Medland, SE, Meinert, S, Meller, T, Nenadic, I, Opel, N, Redlich, R, Reneman, L, Repple, J, Sacchet, MD, Schmitt, S, Schrantee, A, Sim, K, Singh, A, Stein, F, Strike, LT, van Der Wee, NJA, van Der Werff, SJA, Volzke, H, Waltemate, L, Whalley, HC, Wittfeld, K, Wright, MJ, Yang, TT, Zarate, CA, Schmaal, L, Renteria, ME, Campos, A, Thompson, PM, Veltman, DJ, Pozzi, E, van Veltzen, LS, Jahanshad, N, Adams, MJ, Baune, BT, Berger, K, Brosch, K, Bulow, R, Connolly, CG, Dannlowski, U, Davey, CG, de Zubicaray, G, Dima, D, Erwin-Grabner, T, Evans, JW, Fu, CHY, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Grotegerd, D, Harris, MA, Harrison, BJ, Hatton, SN, Hermesdorf, M, Hickie, IB, Ho, TC, Kircher, T, Krug, A, Lagopoulos, J, Lemke, H, McMahon, K, MacMaster, FP, Martin, NG, McIntosh, AM, Medland, SE, Meinert, S, Meller, T, Nenadic, I, Opel, N, Redlich, R, Reneman, L, Repple, J, Sacchet, MD, Schmitt, S, Schrantee, A, Sim, K, Singh, A, Stein, F, Strike, LT, van Der Wee, NJA, van Der Werff, SJA, Volzke, H, Waltemate, L, Whalley, HC, Wittfeld, K, Wright, MJ, Yang, TT, Zarate, CA, Schmaal, L, and Renteria, ME
Abstract: BACKGROUND: Neuroimaging studies of suicidal behavior have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD Working Group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depressive disorder and related phenotypes, including suicidal behavior. METHODS: Here, we pooled data from 18 international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy control subjects and 6448 people with depression, of whom 694 had attempted suicide). We compared regional cortical thickness and surface area and measures of subcortical, lateral ventricular, and intracranial volumes between suicide attempters, clinical control subjects (nonattempters with depression), and healthy control subjects. RESULTS: We identified 25 regions of interest with statistically significant (false discovery rate < .05) differences between groups. Post hoc examinations identified neuroimaging markers associated with suicide attempt including smaller volumes of the left and right thalamus and the right pallidum and lower surface area of the left inferior parietal lobe. CONCLUSIONS: This study addresses the lack of replicability and consistency in several previously published neuroimaging studies of suicide attempt and further demonstrates the need for well-powered samples and collaborative efforts. Our results highlight the potential involvement of the thalamus, a structure viewed historically as a passive gateway in the brain, and the pallidum, a region linked to reward response and positive affect. Future functional and connectivity studies of suicidal behaviors may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.
Published: 2021

31. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author: Sonderby, IE, van der Meer, D, Moreau, C, Kaufmann, T, Walters, GB, Ellegaard, M, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB, Blangero, J, Boomsma, DI, Brodaty, H, Brouwer, RM, Buelow, R, Boen, R, Cahn, W, Calhoun, VD, Caspers, S, Ching, CRK, Cichon, S, Ciufolini, S, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Desrivieres, S, Doherty, JL, Donohoe, G, Draganski, B, Ehrlich, S, Eising, E, Espeseth, T, Fejgin, K, Fisher, SE, Fladby, T, Frei, O, Frouin, V, Fukunaga, M, Gareau, T, Ge, T, Glahn, DC, Grabe, HJ, Groenewold, NA, Gustafsson, O, Haavik, J, Haberg, AK, Hall, J, Hashimoto, R, Hehir-Kwa, JY, Hibar, DP, Hillegers, MHJ, Hoffmann, P, Holleran, L, Holmes, AJ, Homuth, G, Hottenga, J-J, Hulshoff Pol, HE, Ikeda, M, Jahanshad, N, Jockwitz, C, Johansson, S, Joensson, EG, Jorgensen, NR, Kikuchi, M, Knowles, EEM, Kumar, K, Le Hellard, S, Leu, C, Linden, DEJ, Liu, J, Lundervold, A, Lundervold, AJ, Maillard, AM, Martin, NG, Martin-Brevet, S, Mather, KA, Mathias, SR, McMahon, KL, McRae, AF, Medland, SE, Meyer-Lindenberg, A, Moberget, T, Modenato, C, Sanchez, JM, Morris, DW, Muehleisen, TW, Murray, RM, Nielsen, J, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, RA, Owen, MJ, Paus, T, Pausova, Z, Peralta, JM, Pike, GB, Prieto, C, Quinlan, EB, Reinbold, CS, Marques, TR, Rucker, JJH, Sachdev, PS, Sando, SB, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Silva, AI, Sisodiya, SM, Steen, VM, Stein, DJ, Strike, LT, Suzuki, IK, Tamnes, CK, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Uhlmann, A, Ulfarsson, MO, van 't Ent, D, van den Bree, MBM, Vanderhaeghen, P, Vassos, E, Wen, W, Wittfeld, K, Wright, MJ, Agartz, I, Djurovic, S, Westlye, LT, Stefansson, H, Stefansson, K, Jacquemont, S, Thompson, PM, Andreassen, OA, Sonderby, IE, van der Meer, D, Moreau, C, Kaufmann, T, Walters, GB, Ellegaard, M, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB, Blangero, J, Boomsma, DI, Brodaty, H, Brouwer, RM, Buelow, R, Boen, R, Cahn, W, Calhoun, VD, Caspers, S, Ching, CRK, Cichon, S, Ciufolini, S, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Desrivieres, S, Doherty, JL, Donohoe, G, Draganski, B, Ehrlich, S, Eising, E, Espeseth, T, Fejgin, K, Fisher, SE, Fladby, T, Frei, O, Frouin, V, Fukunaga, M, Gareau, T, Ge, T, Glahn, DC, Grabe, HJ, Groenewold, NA, Gustafsson, O, Haavik, J, Haberg, AK, Hall, J, Hashimoto, R, Hehir-Kwa, JY, Hibar, DP, Hillegers, MHJ, Hoffmann, P, Holleran, L, Holmes, AJ, Homuth, G, Hottenga, J-J, Hulshoff Pol, HE, Ikeda, M, Jahanshad, N, Jockwitz, C, Johansson, S, Joensson, EG, Jorgensen, NR, Kikuchi, M, Knowles, EEM, Kumar, K, Le Hellard, S, Leu, C, Linden, DEJ, Liu, J, Lundervold, A, Lundervold, AJ, Maillard, AM, Martin, NG, Martin-Brevet, S, Mather, KA, Mathias, SR, McMahon, KL, McRae, AF, Medland, SE, Meyer-Lindenberg, A, Moberget, T, Modenato, C, Sanchez, JM, Morris, DW, Muehleisen, TW, Murray, RM, Nielsen, J, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, RA, Owen, MJ, Paus, T, Pausova, Z, Peralta, JM, Pike, GB, Prieto, C, Quinlan, EB, Reinbold, CS, Marques, TR, Rucker, JJH, Sachdev, PS, Sando, SB, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Silva, AI, Sisodiya, SM, Steen, VM, Stein, DJ, Strike, LT, Suzuki, IK, Tamnes, CK, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Uhlmann, A, Ulfarsson, MO, van 't Ent, D, van den Bree, MBM, Vanderhaeghen, P, Vassos, E, Wen, W, Wittfeld, K, Wright, MJ, Agartz, I, Djurovic, S, Westlye, LT, Stefansson, H, Stefansson, K, Jacquemont, S, Thompson, PM, and Andreassen, OA
Abstract: Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
Published: 2021

32. Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders (May, 2020, 10.1038/s41380-020-0774-9)

Author: Opel, N, Thalamuthu, A, Milaneschi, Y, Grotegerd, D, Flint, C, Leenings, R, Goltermann, J, Richter, M, Hahn, T, Woditsch, G, Berger, K, Hermesdorf, M, McIntosh, A, Whalley, HC, Harris, MA, MacMaster, FP, Walter, H, Veer, IM, Frodl, T, Carballedo, A, Krug, A, Nenadic, I, Kircher, T, Aleman, A, Groenewold, NA, Stein, DJ, Soares, JC, Zunta-Soares, GB, Mwangi, B, Wu, M-J, Walter, M, Li, M, Harrison, BJ, Davey, CG, Cullen, KR, Klimes-Dougan, B, Mueller, BA, Samann, PG, Penninx, B, Nawijn, L, Veltman, DJ, Aftanas, L, Brak, IV, Filimonova, EA, Osipov, EA, Reneman, L, Schrantee, A, Grabe, HJ, van der Auwera, S, Wittfeld, K, Hosten, N, Volzke, H, Sim, K, Gotlib, IH, Sacchet, MD, Lagopoulos, J, Hatton, SN, Hickie, I, Pozzi, E, Thompson, PM, Jahanshad, N, Schmaal, L, Baune, BT, Dannlowski, U, Opel, N, Thalamuthu, A, Milaneschi, Y, Grotegerd, D, Flint, C, Leenings, R, Goltermann, J, Richter, M, Hahn, T, Woditsch, G, Berger, K, Hermesdorf, M, McIntosh, A, Whalley, HC, Harris, MA, MacMaster, FP, Walter, H, Veer, IM, Frodl, T, Carballedo, A, Krug, A, Nenadic, I, Kircher, T, Aleman, A, Groenewold, NA, Stein, DJ, Soares, JC, Zunta-Soares, GB, Mwangi, B, Wu, M-J, Walter, M, Li, M, Harrison, BJ, Davey, CG, Cullen, KR, Klimes-Dougan, B, Mueller, BA, Samann, PG, Penninx, B, Nawijn, L, Veltman, DJ, Aftanas, L, Brak, IV, Filimonova, EA, Osipov, EA, Reneman, L, Schrantee, A, Grabe, HJ, van der Auwera, S, Wittfeld, K, Hosten, N, Volzke, H, Sim, K, Gotlib, IH, Sacchet, MD, Lagopoulos, J, Hatton, SN, Hickie, I, Pozzi, E, Thompson, PM, Jahanshad, N, Schmaal, L, Baune, BT, and Dannlowski, U
Published: 2021

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

Author: Opel, N, Thalamuthu, A, Milaneschi, Y, Grotegerd, D, Flint, C, Leenings, R, Goltermann, J, Richter, M, Hahn, T, Woditsch, G, Berger, K, Hermesdorf, M, McIntosh, A, Whalley, HC, Harris, MA, MacMaster, FP, Walter, H, Veer, IM, Frodl, T, Carballedo, A, Krug, A, Nenadic, I, Kircher, T, Aleman, A, Groenewold, NA, Stein, DJ, Soares, JC, Zunta-Soares, GB, Mwangi, B, Wu, M-J, Walter, M, Li, M, Harrison, BJ, Davey, CG, Cullen, KR, Klimes-Dougan, B, Mueller, BA, Saemann, PG, Penninx, B, Nawijn, L, Veltman, DJ, Aftanas, L, Brak, I, Filimonova, EA, Osipov, EA, Reneman, L, Schrantee, A, Grabe, HJ, Van der Auwera, S, Wittfeld, K, Hosten, N, Voelzke, H, Sim, K, Gotlib, IH, Sacchet, MD, Lagopoulos, J, Hatton, SN, Hickie, I, Pozzi, E, Thompson, PM, Jahanshad, N, Schmaal, L, Baune, BT, Dannlowski, U, Opel, N, Thalamuthu, A, Milaneschi, Y, Grotegerd, D, Flint, C, Leenings, R, Goltermann, J, Richter, M, Hahn, T, Woditsch, G, Berger, K, Hermesdorf, M, McIntosh, A, Whalley, HC, Harris, MA, MacMaster, FP, Walter, H, Veer, IM, Frodl, T, Carballedo, A, Krug, A, Nenadic, I, Kircher, T, Aleman, A, Groenewold, NA, Stein, DJ, Soares, JC, Zunta-Soares, GB, Mwangi, B, Wu, M-J, Walter, M, Li, M, Harrison, BJ, Davey, CG, Cullen, KR, Klimes-Dougan, B, Mueller, BA, Saemann, PG, Penninx, B, Nawijn, L, Veltman, DJ, Aftanas, L, Brak, I, Filimonova, EA, Osipov, EA, Reneman, L, Schrantee, A, Grabe, HJ, Van der Auwera, S, Wittfeld, K, Hosten, N, Voelzke, H, Sim, K, Gotlib, IH, Sacchet, MD, Lagopoulos, J, Hatton, SN, Hickie, I, Pozzi, E, Thompson, PM, Jahanshad, N, Schmaal, L, Baune, BT, and Dannlowski, U
Abstract: Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.
Published: 2021

34. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author: Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abe, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargallo, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bulow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjo-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Gur, RE, Gur, RC, Haar, S, Haarman, BCM, Haavik, J, Hahn, T, Hajek, T, Harrison, BJ, Harrison, NA, Hartman, CA, Whalley, HC, Heslenfeld, DJ, Hibar, DP, Hilland, E, Hirano, Y, Ho, TC, Hoekstra, PJ, Hoekstra, L, Hohmann, S, Hong, LE, Hoschl, C, Hovik, MF, Howells, FM, Nenadic, I, Jalbrzikowski, M, James, AC, Janssen, J, Jaspers-Fayer, F, Xu, J, Jonassen, R, Karkashadze, G, King, JA, Kircher, T, Kirschner, M, Koch, K, Kochunov, P, Kohls, G, Konrad, K, Kramer, B, Krug, A, Kuntsi, J, Kwon, JS, Landen, M, Landro, NI, Lazaro, L, Lebedeva, IS, Leehr, EJ, Lera-Miguel, S, Lesch, K-P, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Malpas, CB, Portella, MJ, Marsh, R, Martyn, FM, Mataix-Cols, D, Mathalon, DH, McCarthy, H, McDonald, C, McPhilemy, G, Meinert, S, Menchon, JM, Minuzzi, L, Mitchell, PB, Moreno, C, Morgado, P, Muratori, F, Murphy, CM, Murphy, D, Mwangi, B, Nabulsi, L, Nakagawa, A, Nakamae, T, Namazova, L, Narayanaswamy, J, Jahanshad, N, Nguyen, DD, Nicolau, R, O'Gorman Tuura, RL, O'Hearn, K, Oosterlaan, J, Opel, N, Ophoff, RA, Oranje, B, Garcia de la Foz, VO, Overs, BJ, Paloyelis, Y, Pantelis, C, Parellada, M, Pauli, P, Pico-Perez, M, Picon, FA, Piras, F, Plessen, KJ, Pomarol-Clotet, E, Preda, A, Puig, O, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Rauer, L, Reddy, J, Redlich, R, Reif, A, Reneman, L, Repple, J, Retico, A, Richarte, V, Richter, A, Rosa, PGP, Rubia, KK, Hashimoto, R, Sacchet, MD, Salvador, R, Santonja, J, Sarink, K, Sarro, S, Satterthwaite, TD, Sawa, A, Schall, U, Schofield, PR, Schrantee, A, Seitz, J, Serpa, MH, Setien-Suero, E, Shaw, P, Shook, D, Silk, TJ, Sim, K, Simon, S, Simpson, HB, Singh, A, Skoch, A, Skokauskas, N, Soares, JC, Soreni, N, Soriano-Mas, C, Spalletta, G, Spaniel, F, Lawrie, SM, Stern, ER, Stewart, SE, Takayanagi, Y, Temmingh, HS, Tolin, DF, Tomecek, D, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, van Amelsvoort, T, van der Wee, NJA, van der Werff, SJA, van Haren, NEM, van Wingen, GA, Vance, A, Vazquez-Bourgon, J, Vecchio, D, Venkatasubramanian, G, Vieta, E, Vilarroya, O, Vives-Gilabert, Y, Voineskos, AN, Volzke, H, von Polier, GG, Walton, E, Weickert, TW, Weickert, CS, Weideman, AS, Wittfeld, K, Wolf, DH, Wu, M-J, Yang, TT, Yang, K, Yoncheva, Y, Yun, J-Y, Cheng, Y, Zanetti, MV, Ziegler, GC, Franke, B, Hoogman, M, Buitelaar, JK, van Rooij, D, Andreassen, OA, Ching, CRK, Veltman, DJ, Schmaal, L, Stein, DJ, van den Heuvel, OA, Turner, JA, van Erp, TGM, Pausova, Z, Thompson, PM, Paus, T, Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abe, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargallo, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bulow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjo-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Gur, RE, Gur, RC, Haar, S, Haarman, BCM, Haavik, J, Hahn, T, Hajek, T, Harrison, BJ, Harrison, NA, Hartman, CA, Whalley, HC, Heslenfeld, DJ, Hibar, DP, Hilland, E, Hirano, Y, Ho, TC, Hoekstra, PJ, Hoekstra, L, Hohmann, S, Hong, LE, Hoschl, C, Hovik, MF, Howells, FM, Nenadic, I, Jalbrzikowski, M, James, AC, Janssen, J, Jaspers-Fayer, F, Xu, J, Jonassen, R, Karkashadze, G, King, JA, Kircher, T, Kirschner, M, Koch, K, Kochunov, P, Kohls, G, Konrad, K, Kramer, B, Krug, A, Kuntsi, J, Kwon, JS, Landen, M, Landro, NI, Lazaro, L, Lebedeva, IS, Leehr, EJ, Lera-Miguel, S, Lesch, K-P, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Malpas, CB, Portella, MJ, Marsh, R, Martyn, FM, Mataix-Cols, D, Mathalon, DH, McCarthy, H, McDonald, C, McPhilemy, G, Meinert, S, Menchon, JM, Minuzzi, L, Mitchell, PB, Moreno, C, Morgado, P, Muratori, F, Murphy, CM, Murphy, D, Mwangi, B, Nabulsi, L, Nakagawa, A, Nakamae, T, Namazova, L, Narayanaswamy, J, Jahanshad, N, Nguyen, DD, Nicolau, R, O'Gorman Tuura, RL, O'Hearn, K, Oosterlaan, J, Opel, N, Ophoff, RA, Oranje, B, Garcia de la Foz, VO, Overs, BJ, Paloyelis, Y, Pantelis, C, Parellada, M, Pauli, P, Pico-Perez, M, Picon, FA, Piras, F, Plessen, KJ, Pomarol-Clotet, E, Preda, A, Puig, O, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Rauer, L, Reddy, J, Redlich, R, Reif, A, Reneman, L, Repple, J, Retico, A, Richarte, V, Richter, A, Rosa, PGP, Rubia, KK, Hashimoto, R, Sacchet, MD, Salvador, R, Santonja, J, Sarink, K, Sarro, S, Satterthwaite, TD, Sawa, A, Schall, U, Schofield, PR, Schrantee, A, Seitz, J, Serpa, MH, Setien-Suero, E, Shaw, P, Shook, D, Silk, TJ, Sim, K, Simon, S, Simpson, HB, Singh, A, Skoch, A, Skokauskas, N, Soares, JC, Soreni, N, Soriano-Mas, C, Spalletta, G, Spaniel, F, Lawrie, SM, Stern, ER, Stewart, SE, Takayanagi, Y, Temmingh, HS, Tolin, DF, Tomecek, D, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, van Amelsvoort, T, van der Wee, NJA, van der Werff, SJA, van Haren, NEM, van Wingen, GA, Vance, A, Vazquez-Bourgon, J, Vecchio, D, Venkatasubramanian, G, Vieta, E, Vilarroya, O, Vives-Gilabert, Y, Voineskos, AN, Volzke, H, von Polier, GG, Walton, E, Weickert, TW, Weickert, CS, Weideman, AS, Wittfeld, K, Wolf, DH, Wu, M-J, Yang, TT, Yang, K, Yoncheva, Y, Yun, J-Y, Cheng, Y, Zanetti, MV, Ziegler, GC, Franke, B, Hoogman, M, Buitelaar, JK, van Rooij, D, Andreassen, OA, Ching, CRK, Veltman, DJ, Schmaal, L, Stein, DJ, van den Heuvel, OA, Turner, JA, van Erp, TGM, Pausova, Z, Thompson, PM, and Paus, T
Abstract: IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene
Published: 2021

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

Author: Han, LKM, Dinga, R, Hahn, T, Ching, CRK, Eyler, LT, Aftanas, L, Aghajani, M, Aleman, A, Baune, BT, Berger, K, Brak, I, Busatto Filho, G, Carballedo, A, Connolly, CG, Couvy-Duchesne, B, Cullen, KR, Dannlowski, U, Davey, CG, Dima, D, Duran, FLS, Enneking, V, Filimonova, E, Frenzel, S, Frodl, T, Fu, CHY, Godlewska, BR, Gotlib, IH, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Hall, GB, Harrison, BJ, Hatton, SN, Hermesdorf, M, Hickie, IB, Ho, TC, Hosten, N, Jansen, A, Kaehler, C, Kircher, T, Klimes-Dougan, B, Kraemer, B, Krug, A, Lagopoulos, J, Leenings, R, MacMaster, FP, MacQueen, G, McIntosh, A, McLellan, Q, McMahon, KL, Medland, SE, Mueller, BA, Mwangi, B, Osipov, E, Portella, MJ, Pozzi, E, Reneman, L, Repple, J, Rosa, PGP, Sacchet, MD, Saemann, PG, Schnell, K, Schrantee, A, Simulionyte, E, Soares, JC, Sommer, J, Stein, DJ, Steinstraeter, O, Strike, LT, Thomopoulos, SI, van Tol, M-J, Veer, IM, Vermeiren, RRJM, Walter, H, van der Wee, NJA, van der Werff, SJA, Whalley, H, Winter, NR, Wittfeld, K, Wright, MJ, Wu, M-J, Voelzke, H, Yang, TT, Zannias, V, de Zubicaray, GI, Zunta-Soares, GB, Abe, C, Alda, M, Andreassen, OA, Boen, E, Bonnin, CM, Canales-Rodriguez, EJ, Cannon, D, Caseras, X, Chaim-Avancini, TM, Elvsashagen, T, Favre, P, Foley, SF, Fullerton, JM, Goikolea, JM, Haarman, BCM, Hajek, T, Henry, C, Houenou, J, Howells, FM, Ingvar, M, Kuplicki, R, Lafer, B, Landen, M, Machado-Vieira, R, Malt, UF, McDonald, C, Mitchell, PB, Nabulsi, L, Otaduy, MCG, Overs, BJ, Polosan, M, Pomarol-Clotet, E, Radua, J, Rive, MM, Roberts, G, Ruhe, HG, Salvador, R, Sarro, S, Satterthwaite, TD, Savitz, J, Schene, AH, Schofield, PR, Serpa, MH, Sim, K, Soeiro-de-Souza, MG, Sutherland, AN, Temmingh, HS, Timmons, GM, Uhlmann, A, Vieta, E, Wolf, DH, Zanetti, MV, Jahanshad, N, Thompson, PM, Veltman, DJ, Penninx, BWJH, Marquand, AF, Cole, JH, Schmaal, L, Han, LKM, Dinga, R, Hahn, T, Ching, CRK, Eyler, LT, Aftanas, L, Aghajani, M, Aleman, A, Baune, BT, Berger, K, Brak, I, Busatto Filho, G, Carballedo, A, Connolly, CG, Couvy-Duchesne, B, Cullen, KR, Dannlowski, U, Davey, CG, Dima, D, Duran, FLS, Enneking, V, Filimonova, E, Frenzel, S, Frodl, T, Fu, CHY, Godlewska, BR, Gotlib, IH, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Hall, GB, Harrison, BJ, Hatton, SN, Hermesdorf, M, Hickie, IB, Ho, TC, Hosten, N, Jansen, A, Kaehler, C, Kircher, T, Klimes-Dougan, B, Kraemer, B, Krug, A, Lagopoulos, J, Leenings, R, MacMaster, FP, MacQueen, G, McIntosh, A, McLellan, Q, McMahon, KL, Medland, SE, Mueller, BA, Mwangi, B, Osipov, E, Portella, MJ, Pozzi, E, Reneman, L, Repple, J, Rosa, PGP, Sacchet, MD, Saemann, PG, Schnell, K, Schrantee, A, Simulionyte, E, Soares, JC, Sommer, J, Stein, DJ, Steinstraeter, O, Strike, LT, Thomopoulos, SI, van Tol, M-J, Veer, IM, Vermeiren, RRJM, Walter, H, van der Wee, NJA, van der Werff, SJA, Whalley, H, Winter, NR, Wittfeld, K, Wright, MJ, Wu, M-J, Voelzke, H, Yang, TT, Zannias, V, de Zubicaray, GI, Zunta-Soares, GB, Abe, C, Alda, M, Andreassen, OA, Boen, E, Bonnin, CM, Canales-Rodriguez, EJ, Cannon, D, Caseras, X, Chaim-Avancini, TM, Elvsashagen, T, Favre, P, Foley, SF, Fullerton, JM, Goikolea, JM, Haarman, BCM, Hajek, T, Henry, C, Houenou, J, Howells, FM, Ingvar, M, Kuplicki, R, Lafer, B, Landen, M, Machado-Vieira, R, Malt, UF, McDonald, C, Mitchell, PB, Nabulsi, L, Otaduy, MCG, Overs, BJ, Polosan, M, Pomarol-Clotet, E, Radua, J, Rive, MM, Roberts, G, Ruhe, HG, Salvador, R, Sarro, S, Satterthwaite, TD, Savitz, J, Schene, AH, Schofield, PR, Serpa, MH, Sim, K, Soeiro-de-Souza, MG, Sutherland, AN, Temmingh, HS, Timmons, GM, Uhlmann, A, Vieta, E, Wolf, DH, Zanetti, MV, Jahanshad, N, Thompson, PM, Veltman, DJ, Penninx, BWJH, Marquand, AF, Cole, JH, and Schmaal, L
Abstract: Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
Published: 2021

36. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author: Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S.I., Pozzi, E., Abe, Y., Abé, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S.H., Anagnostou, E., McIntosh, A.A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C.E., Baranov, A., Bargalló, N., Bau, C.H.D., Baumeister, S., Baune, B.T., Bellgrove, M.A., Benedetti, F., Bertolino, A., Boedhoe, P.S.W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B.P., Bruggemann, J.M., Bülow, R., Busatto, G.F., Calderoni, S., Calhoun, V.D., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carr, V.J., Cascella, N., Cercignani, M., Chaim-Avancini, T.M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A.I., Cullen, K.R., Cupertino, R.B., Daly, E., Dannlowski, U., Davey, C.G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E.W., Dima, D., Dohm, K., Ehrlich, S., Ely, B.A., Erwin-Grabner, T., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V., Fatjó-Vilas, M., Fedor, J.M., Fitzgerald, K.D., Ford, J.M., Frodl, T., Fu, C.H.Y., Fullerton, J.M., Gabel, M.C., Glahn, D.C., Roberts, G., Gogberashvili, T., Goikolea, J.M., Gotlib, I.H., Goya-Maldonado, R., Grabe, H.J., Green, M.J., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R.E., Gur, R.C., Haar, S., Haarman, B.C.M., Haavik, J., Hahn, T., Hajek, T., Harrison, B.J., Harrison, N.A., Hartman, C.A., Whalley, H.C., Heslenfeld, D.J., Hibar, D.P., Hilland, E., Hirano, Y., Ho, T.C., Hoekstra, P.J., Hoekstra, L., Hohmann, S., Hong, L.E., Höschl, C., Høvik, M.F., Howells, F.M., Nenadic, I., Jalbrzikowski, M., James, A.C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J.A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Krämer, B., Krug, A., Kuntsi, J., Kwon, J.S., Landén, M., Landrø, N.I., Lazaro, L., Lebedeva, I.S., Leehr, E.J., Lera-Miguel, S., Lesch, K.-P., Lochner, C., Louza, M.R., Luna, B., Lundervold, A.J., Macmaster, F.P., Maglanoc, L.A., Malpas, C.B., Portella, M.J., Marsh, R., Martyn, F.M., Mataix-Cols, D., Mathalon, D.H., McCarthy, H., McDonald, C., McPhilemy, G., Meinert, S., Menchón, J.M., Minuzzi, L., Mitchell, P.B., Moreno, C., Morgado, P., Muratori, F., Murphy, C.M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D.D., Nicolau, R., O'Gorman Tuura, R.L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R.A., Oranje, B., García De La Foz, V.O., Overs, B.J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Picó-Pérez, M., Picon, F.A., Piras, F., Plessen, K.J., Pomarol-Clotet, E., Preda, A., Puig, O., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P.G.P., Rubia, K.K., Hashimoto, R., Sacchet, M.D., Salvador, R., Santonja, J., Sarink, K., Sarró, S., Satterthwaite, T.D., Sawa, A., Schall, U., Schofield, P.R., Schrantee, A., Seitz, J., Serpa, M.H., Setién-Suero, E., Shaw, P., Shook, D., Silk, T.J., Sim, K., Simon, S., Simpson, H.B., Singh, A., Skoch, A., Skokauskas, N., Soares, J.C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S.M., Stern, E.R., Stewart, S.E., Takayanagi, Y., Temmingh, H.S., Tolin, D.F., Tomecek, D., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N.J.A., Van Der Werff, S.J.A., Van Haren, N.E.M., Van Wingen, G.A., Vance, A., Vázquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A.N., Völzke, H., Von Polier, G.G., Walton, E., Weickert, T.W., Weickert, C.S., Weideman, A.S., Wittfeld, K., Wolf, D.H., Wu, M.-J., Yang, T.T., Yang, K., Yoncheva, Y., Yun, J.-Y., Cheng, Y., Zanetti, M.V., Ziegler, G.C., Franke, B., Hoogman, M., Buitelaar, J.K., Van Rooij, D., Andreassen, O.A., Ching, C.R.K., Veltman, D.J., Schmaal, L., Stein, D.J., Van Den Heuvel, O.A., Turner, J.A., Van Erp, T.G.M., Pausova, Z., Thompson, P.M., Paus, T., Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S.I., Pozzi, E., Abe, Y., Abé, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S.H., Anagnostou, E., McIntosh, A.A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C.E., Baranov, A., Bargalló, N., Bau, C.H.D., Baumeister, S., Baune, B.T., Bellgrove, M.A., Benedetti, F., Bertolino, A., Boedhoe, P.S.W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B.P., Bruggemann, J.M., Bülow, R., Busatto, G.F., Calderoni, S., Calhoun, V.D., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carr, V.J., Cascella, N., Cercignani, M., Chaim-Avancini, T.M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A.I., Cullen, K.R., Cupertino, R.B., Daly, E., Dannlowski, U., Davey, C.G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E.W., Dima, D., Dohm, K., Ehrlich, S., Ely, B.A., Erwin-Grabner, T., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V., Fatjó-Vilas, M., Fedor, J.M., Fitzgerald, K.D., Ford, J.M., Frodl, T., Fu, C.H.Y., Fullerton, J.M., Gabel, M.C., Glahn, D.C., Roberts, G., Gogberashvili, T., Goikolea, J.M., Gotlib, I.H., Goya-Maldonado, R., Grabe, H.J., Green, M.J., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R.E., Gur, R.C., Haar, S., Haarman, B.C.M., Haavik, J., Hahn, T., Hajek, T., Harrison, B.J., Harrison, N.A., Hartman, C.A., Whalley, H.C., Heslenfeld, D.J., Hibar, D.P., Hilland, E., Hirano, Y., Ho, T.C., Hoekstra, P.J., Hoekstra, L., Hohmann, S., Hong, L.E., Höschl, C., Høvik, M.F., Howells, F.M., Nenadic, I., Jalbrzikowski, M., James, A.C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J.A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Krämer, B., Krug, A., Kuntsi, J., Kwon, J.S., Landén, M., Landrø, N.I., Lazaro, L., Lebedeva, I.S., Leehr, E.J., Lera-Miguel, S., Lesch, K.-P., Lochner, C., Louza, M.R., Luna, B., Lundervold, A.J., Macmaster, F.P., Maglanoc, L.A., Malpas, C.B., Portella, M.J., Marsh, R., Martyn, F.M., Mataix-Cols, D., Mathalon, D.H., McCarthy, H., McDonald, C., McPhilemy, G., Meinert, S., Menchón, J.M., Minuzzi, L., Mitchell, P.B., Moreno, C., Morgado, P., Muratori, F., Murphy, C.M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D.D., Nicolau, R., O'Gorman Tuura, R.L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R.A., Oranje, B., García De La Foz, V.O., Overs, B.J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Picó-Pérez, M., Picon, F.A., Piras, F., Plessen, K.J., Pomarol-Clotet, E., Preda, A., Puig, O., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P.G.P., Rubia, K.K., Hashimoto, R., Sacchet, M.D., Salvador, R., Santonja, J., Sarink, K., Sarró, S., Satterthwaite, T.D., Sawa, A., Schall, U., Schofield, P.R., Schrantee, A., Seitz, J., Serpa, M.H., Setién-Suero, E., Shaw, P., Shook, D., Silk, T.J., Sim, K., Simon, S., Simpson, H.B., Singh, A., Skoch, A., Skokauskas, N., Soares, J.C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S.M., Stern, E.R., Stewart, S.E., Takayanagi, Y., Temmingh, H.S., Tolin, D.F., Tomecek, D., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N.J.A., Van Der Werff, S.J.A., Van Haren, N.E.M., Van Wingen, G.A., Vance, A., Vázquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A.N., Völzke, H., Von Polier, G.G., Walton, E., Weickert, T.W., Weickert, C.S., Weideman, A.S., Wittfeld, K., Wolf, D.H., Wu, M.-J., Yang, T.T., Yang, K., Yoncheva, Y., Yun, J.-Y., Cheng, Y., Zanetti, M.V., Ziegler, G.C., Franke, B., Hoogman, M., Buitelaar, J.K., Van Rooij, D., Andreassen, O.A., Ching, C.R.K., Veltman, D.J., Schmaal, L., Stein, D.J., Van Den Heuvel, O.A., Turner, J.A., Van Erp, T.G.M., Pausova, Z., Thompson, P.M., and Paus, T.
Abstract: Importance Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. Objective To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. Design, Setting, and Participants Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. Main Outcomes and Measures Interregional profiles of group difference in cortical thickness between cases and controls. Results A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (exce
Published: 2021
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37. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M., Suzuki, H., Jian, X.Q., Sarnowski, C., Evans, T.E., Bis, J.C., Eiriksdottir, G., Sakaue, S., Terzikhan, N., Habes, M., Zhao, W., Armstrong, N.J., Hofer, E., Yanek, L.R., Hagenaars, S.P., Kumar, R.B., Akker, E.B. van den, McWhirter, R.E., Trompet, S., Mishra, A., Saba, Y., Satizabal, C.L., Beaudet, G., Petit, L., Tsuchida, A., Zago, L., Schilling, S., Sigurdsson, S., Gottesman, R.F., Lewis, C.E., Aggarwal, N.T., Lopez, O.L., Smith, J.A., Hernandez, M.C.V., Grond, J. van der, Wright, M.J., Knol, M.J., Dorr, M., Thomson, R.J., Bordes, C., Grand, Q. le, Duperron, M.G., Smith, A.V., Knopman, D.S., Schreiner, P.J., Evans, D.A., Rotter, J.I., Beiser, A.S., Maniega, S.M., Beekman, M., Trollor, J., Stott, D.J., Vernooij, M.W., Wittfeld, K., Niessen, W.J., Soumare, A., Boerwinkle, E., Sidney, S., Turner, S.T., Davies, G., Thalamuthu, A., Volker, U., Buchem, M.A. van, Bryan, R.N., Dupuis, J., Bastin, M.E., Ames, D., Teumer, A., Amouyel, P., Kwok, J.B., Bulow, R., Deary, I.J., Schofield, P.R., Brodaty, H., Jiang, J.Y., Tabara, Y., Setoh, K., Miyamoto, S., Yoshida, K., Nagata, M., Kamatani, Y., Matsuda, F., Psaty, B.M., Bennett, D.A., Jager, P.L. de, Mosley, T.H., Sachdev, P.S., Schmidt, R., Warren, H.R., Evangelou, E., Tregouet, D.A., Ikram, M.A., Wen, W., DeCarli, C., Srikanth, V.K., Jukema, J.W., Slagboom, E.P., Kardia, S.L.R., Okada, Y., Mazoyer, B., Wardlaw, J.M., Nyquist, P.A., Mather, K.A., Grabe, H.J., Schmidt, H., Duijn, C.M. van, Gudnason, V., Longstreth, W.T., Launer, L.J., Lathrop, M., Seshadri, S., Tzourio, C., Adams, H.H., Matthews, P.M., Fornage, M., Debette, S., Int Network Thrombosis INVENT Cons, and Int Headache Genomics Consortium I
Subjects: Adult, Male, Science, BLOOD-PRESSURE, Risk Assessment, behavioral disciplines and activities, GENETIC ARCHITECTURE, Young Adult, Alzheimer Disease, Risk Factors, mental disorders, WHITE-MATTER HYPERINTENSITIES, WIDE ASSOCIATION, Humans, International Headache Genomics Consortium (IHGC), CELL-TYPES, Medical History Taking, METAANALYSIS, AGING RESEARCH, Aged, RISK, Aged, 80 and over, Science & Technology, Mendelian Randomization Analysis, Middle Aged, COGNITIVE IMPAIRMENT, White Matter, Multidisciplinary Sciences, Stroke, Diffusion Tensor Imaging, Genetic Loci, Cerebral Small Vessel Diseases, Hypertension, MENDELIAN RANDOMIZATION, Science & Technology - Other Topics, Female, International Network against Thrombosis (INVENT) Consortium, Genome-Wide Association Study
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p=2.5x10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials. White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.
Published: 2020

38. A genome-wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschlʼs gyrus

Author: Cai, D.-C., Fonteijn, H., Guadalupe, T., Zwiers, M., Wittfeld, K., Teumer, A., Hoogman, M., Arias-Vásquez, A., Yang, Y., Buitelaar, J., Fernández, G., Brunner, H. G., van Bokhoven, H., Franke, B., Hegenscheid, K., Homuth, G., Fisher, S. E., Grabe, H. J., Francks, C., and Hagoort, P.
Published: 2014
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39. Genetic variants for head size share genes and pathways with cancer

Author: Shihua Li, Melissa J. Green, Nagata M, Miyamoto S, Le Grand Q, Pourcain Bs, Grabe Hj, Catherine Helmer, William R. Reay, Nele Friedrich, Mazoyer B, Seshadri S, Per Hoffmann, Simon Haworth, Veronica Witte A, Yang Q, Max Lam, Teunissen Mw, Fang-Chi Hsu, Debette S, Murray J. Cairns, Amod Ar, Setoh K, Windham Bg, Shareefa Dalvie, Georg Homuth, Charlie S. DeCarli, Gennady V. Roshchupkin, Céline S. Reinbold, Mühleisen Tw, Nakahara S, Van der Auwera S, Xueqiu Jian, Cecil Ca, Jean-François Dartigues, Alexa S. Beiser, Stein Jl, Houlden H, Christiane Jockwitz, Moebus S, Claudia L. Satizabal, Tavia E. Evans, Matsuda F, Cora E. Lewis, Wittfeld K, Calhoun Vd, van der Lugt A, Teumer A, Pausova Z, W. T. Longstreth, Aniket Mishra, Tomáš Paus, Vernooij Mw, Medland Se, Palmer Nd, Ahmad R. Hariri, Adrian Preda, Clifford R. Jack, van Erp Tg, Amaia Carrion-Castillo, Werring Dj, Gwénaëlle Catheline, Asta Håberg, Robin Bülow, Sven Cichon, Yann Quidé, Muetzel R, Tabara Y, Sidney S, Cheung C, Brunner Hg, Annchen R. Knodt, Mosley Th, van Dam-Nolen Dh, Hostettler Ic, Jean Shin, Shapland Cy, Reut Avinun, Crivello F, Mäkitie O, Fornage M, Yoshida K, Villringer A, Lim K, Schreiner Pj, Bowden Dw, Thompson Pm, Daniel Bos, Uhlmann A, Enlund-Cerullo M, Schmidt R, Hieab H.H. Adams, Neda Jahanshad, Frauke Beyer, Gloria H.Y. Li, Fabio Macciardi, Lamballais S, Kämpe A, Judith M. Ford, Poot Ra, J. C. Bis, Yoichiro Kamatani, Ami Tsuchida, Markus Scholz, Ikram Ma, Andersson S, Lenore J. Launer, Stein Dj, Koudstaal Pj, Barry I. Freedman, Barbara Franke, Ikram Mk, Sim K, Marie-Gabrielle Duperron, Bryan Rn, Svenja Caspers, Pawlak Ma, Tonya White, Maria J. Knol, Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, and Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium
Subjects: Genetics, 0303 health sciences, education.field_of_study, biology, Population, Wnt signaling pathway, Macrocephaly, Cancer, medicine.disease, Biological pathway, 03 medical and health sciences, 0302 clinical medicine, medicine, biology.protein, PTEN, Human height, medicine.symptom, education, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: The size of the human head is determined by growth in the first years of life, while the rest of the body typically grows until early adulthood1. Such complex developmental processes are regulated by various genes and growth pathways2. Rare genetic syndromes have revealed genes that affect head size3, but the genetic drivers of variation in head size within the general population remain largely unknown. To elucidate biological pathways underlying the growth of the human head, we performed the largest genome-wide association study on human head size to date (N = 79,107). We identified 67 genetic loci, 50 of which are novel, and found that these loci are preferentially associated with head size and mostly independent from height. In subsequent neuroimaging analyses, the majority of genetic variants demonstrated widespread effects on the brain, whereas the effects of 17 variants could be localized to one or two specific brain regions. Through hypothesis-free approaches, we find a strong overlap of head size variants with both cancer pathways and cancer genes. Gene set analyses showed enrichment for different types of cancer and the p53, Wnt and ErbB signalling pathway. Genes overlapping or close to lead variants – such as TP53, PTEN and APC – were enriched for genes involved in macrocephaly syndromes (up to 37-fold) and high-fidelity cancer genes (up to 9-fold), whereas this enrichment was not seen for human height variants. This indicates that genes regulating early brain and cranial growth are associated with a propensity to neoplasia later in life, irrespective of height. Our results warrant further investigations of the link between head size and cancer, as well as its clinical implications in the general population.
Published: 2020

40. Cereb Cortex

Author: Shin, J., Ma, S., Hofer, E., Patel, Y., VOSBERG, D. E., TILLEY, S., ROSHCHUPKIN, G. V., SOUSA, A. M. M., JIAN, X., GOTTESMAN, R., MOSLEY, T. H., FORNAGE, M., SABA, Y., PIRPAMER, L., Schmidt, R., Schmidt, H., CARRION-CASTILLO, A., Crivello, F., Mazoyer, B., BIS, J. C., Li, S., Yang, Q., LUCIANO, M., Karama, S., Lewis, L., BASTIN, M. E., HARRIS, M. A., WARDLAW, J. M., DEARY, I. E., Scholz, M., Loeffler, M., WITTE, A. V., Beyer, F., VILLRINGER, A., ARMSTRONG, N. J., MATHER, K. A., Ames, D., Jiang, J., KWOK, J. B., SCHOFIELD, P. R., THALAMUTHU, A., TROLLOR, J. N., WRIGHT, M. J., BRODATY, H., Wen, W., SACHDEV, P. S., TERZIKHAN, N., EVANS, T. E., ADAMS, Hhhh, Ikram, M. A., FRENZEL, S., AUWERA-PALITSCHKA, S. V., WITTFELD, K., BULOW, R., Grabe, H. J., Tzourio, Christophe, Mishra, Aniket, MAINGAULT, S., Debette, Stéphanie, GILLESPIE, N. A., FRANZ, C. E., KREMEN, W. S., Ding, L., JAHANSHAD, N., Sestan, N., PAUSOVA, Z., SESHADRI, S., PAUS, T., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: endocrine system, VINTAGE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade—albeit in a very limited manner—to behaviors as complex as the choice of one’s occupation.
Published: 2020

41. Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Author: Hofer, E., Roshchupkin, G.V., Adams, H.H.H., Knol, M.J., Lin, H., Li, S., Zare, H., Ahmad, S., Armstrong, N.J., Satizabal, C.L., Bernard, M., Bis, J.C., Gillespie, N.A., Luciano, M., Mishra, A., Scholz, M., Teumer, A., Xia, R., Jian, X., Mosley, T.H., Saba, Y., Pirpamer, L., Seiler, S., Becker, J.T., Carmichael, O., Rotter, J.I., Psaty, B.M., Lopez, O.L., Amin, N., van der Lee, S.J., Yang, Q., Himali, J.J., Maillard, P., Beiser, A.S., DeCarli, C., Karama, S., Lewis, L., Harris, M., Bastin, M.E., Deary, I.J., Veronica Witte, A., Beyer, F., Loeffler, M., Mather, K.A., Schofield, P.R., Thalamuthu, A., Kwok, J.B., Wright, M.J., Ames, D., Trollor, J., Jiang, J., Brodaty, H., Wen, W., Vernooij, M.W., Hofman, A., Uitterlinden, A.G., Niessen, W.J., Wittfeld, K., Bülow, R., Völker, U., Pausova, Z., Bruce Pike, G., Maingault, S., Crivello, F., Tzourio, C., Amouyel, P., Mazoyer, B., Neale, M.C., Franz, C.E., Lyons, M.J., Panizzon, M.S., Andreassen, O.A., Dale, A.M., Logue, M.A., Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Stein, J.L., Thompson, P.M., Medland, S.E., Sachdev, P.S., Kremen, W.S., Wardlaw, J.M., Villringer, A., van Duijn, C.M., Grabe, H.J., Longstreth, W.T., Fornage, M., Paus, T., Debette, S., Arfan Ikram, M., Schmidt, H., Schmidt, R., Seshadri, S., Hofer, E., Roshchupkin, G.V., Adams, H.H.H., Knol, M.J., Lin, H., Li, S., Zare, H., Ahmad, S., Armstrong, N.J., Satizabal, C.L., Bernard, M., Bis, J.C., Gillespie, N.A., Luciano, M., Mishra, A., Scholz, M., Teumer, A., Xia, R., Jian, X., Mosley, T.H., Saba, Y., Pirpamer, L., Seiler, S., Becker, J.T., Carmichael, O., Rotter, J.I., Psaty, B.M., Lopez, O.L., Amin, N., van der Lee, S.J., Yang, Q., Himali, J.J., Maillard, P., Beiser, A.S., DeCarli, C., Karama, S., Lewis, L., Harris, M., Bastin, M.E., Deary, I.J., Veronica Witte, A., Beyer, F., Loeffler, M., Mather, K.A., Schofield, P.R., Thalamuthu, A., Kwok, J.B., Wright, M.J., Ames, D., Trollor, J., Jiang, J., Brodaty, H., Wen, W., Vernooij, M.W., Hofman, A., Uitterlinden, A.G., Niessen, W.J., Wittfeld, K., Bülow, R., Völker, U., Pausova, Z., Bruce Pike, G., Maingault, S., Crivello, F., Tzourio, C., Amouyel, P., Mazoyer, B., Neale, M.C., Franz, C.E., Lyons, M.J., Panizzon, M.S., Andreassen, O.A., Dale, A.M., Logue, M.A., Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Stein, J.L., Thompson, P.M., Medland, S.E., Sachdev, P.S., Kremen, W.S., Wardlaw, J.M., Villringer, A., van Duijn, C.M., Grabe, H.J., Longstreth, W.T., Fornage, M., Paus, T., Debette, S., Arfan Ikram, M., Schmidt, H., Schmidt, R., and Seshadri, S.
Abstract: Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
Published: 2020

42. Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia

Author: Sønderby, I.E., Gústafsson, Ó., Doan, N.T., Hibar, D.P., Martin-Brevet, S., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N., Blangero, J., Boomsma, D.I., Bralten, J., Brattbak, H-R, Brodaty, H., Brouwer, R.M., Bülow, R., Calhoun, V., Caspers, S., Cavalleri, G., Chen, C-H, Cichon, S., Ciufolini, S., Corvin, A., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Delanty, N., den Braber, A., Desrivières, S., Donohoe, G., Draganski, B., Ehrlich, S., Espeseth, T., Fisher, S.E., Franke, B., Frouin, V., Fukunaga, M., Gareau, T., Glahn, D.C., Grabe, H., Groenewold, N.A., Haavik, J., Håberg, A., Hashimoto, R., Hehir-Kwa, J.Y., Heinz, A., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Hottenga, J-J, Hulshoff, H.E., Ikeda, M., Jahanshad, N., Jernigan, T., Jockwitz, C., Johansson, S., Jonsdottir, G.A., Jönsson, E.G., Kahn, R., Kaufmann, T., Kelly, S., Kikuchi, M., Knowles, E.E.M., Kolskår, K.K., Kwok, J.B., Hellard, S.L., Leu, C., Liu, J., Lundervold, A.J., Lundervold, A., Martin, N.G., Mather, K., Mathias, S.R., McCormack, M., McMahon, K.L., McRae, A., Milaneschi, Y., Moreau, C., Morris, D., Mothersill, D., Mühleisen, T.W., Murray, R., Nordvik, J.E., Nyberg, L., Olde Loohuis, L.M., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Peralta, J.M., Pike, B., Prieto, C., Pudas, S., Quinlan, E., Quintana, D.S., Reinbold, C.S., Marques, T.R., Reymond, A., Richard, G., Rodriguez-Herreros, B., Roiz-Santiañez, R., Rokicki, J., Rucker, J., Sachdev, P., Sanders, A-M, Sando, S.B., Schmaal, L., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Sisodiya, S., Steen, V.M., Stein, D.J., Steinberg, S., Strike, L., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J., Ueland, T., Uhlmann, A., Ulfarsson, M.O., van ’t Ent, D., van der Meer, D., van Haren, N.E.M., Vaskinn, A., Vassos, E., Walters, G.B., Wang, Y., Wen, W., Whelan, C.D., Wittfeld, K., Wright, M., Yamamori, H., Zayats, T., Agartz, I., Westlye, L.T., Jacquemont, S., Djurovic, S., Stefánsson, H., Stefánsson, K., Thompson, P., Andreassen, O.A., Sønderby, I.E., Gústafsson, Ó., Doan, N.T., Hibar, D.P., Martin-Brevet, S., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N., Blangero, J., Boomsma, D.I., Bralten, J., Brattbak, H-R, Brodaty, H., Brouwer, R.M., Bülow, R., Calhoun, V., Caspers, S., Cavalleri, G., Chen, C-H, Cichon, S., Ciufolini, S., Corvin, A., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Delanty, N., den Braber, A., Desrivières, S., Donohoe, G., Draganski, B., Ehrlich, S., Espeseth, T., Fisher, S.E., Franke, B., Frouin, V., Fukunaga, M., Gareau, T., Glahn, D.C., Grabe, H., Groenewold, N.A., Haavik, J., Håberg, A., Hashimoto, R., Hehir-Kwa, J.Y., Heinz, A., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Hottenga, J-J, Hulshoff, H.E., Ikeda, M., Jahanshad, N., Jernigan, T., Jockwitz, C., Johansson, S., Jonsdottir, G.A., Jönsson, E.G., Kahn, R., Kaufmann, T., Kelly, S., Kikuchi, M., Knowles, E.E.M., Kolskår, K.K., Kwok, J.B., Hellard, S.L., Leu, C., Liu, J., Lundervold, A.J., Lundervold, A., Martin, N.G., Mather, K., Mathias, S.R., McCormack, M., McMahon, K.L., McRae, A., Milaneschi, Y., Moreau, C., Morris, D., Mothersill, D., Mühleisen, T.W., Murray, R., Nordvik, J.E., Nyberg, L., Olde Loohuis, L.M., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Peralta, J.M., Pike, B., Prieto, C., Pudas, S., Quinlan, E., Quintana, D.S., Reinbold, C.S., Marques, T.R., Reymond, A., Richard, G., Rodriguez-Herreros, B., Roiz-Santiañez, R., Rokicki, J., Rucker, J., Sachdev, P., Sanders, A-M, Sando, S.B., Schmaal, L., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Sisodiya, S., Steen, V.M., Stein, D.J., Steinberg, S., Strike, L., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J., Ueland, T., Uhlmann, A., Ulfarsson, M.O., van ’t Ent, D., van der Meer, D., van Haren, N.E.M., Vaskinn, A., Vassos, E., Walters, G.B., Wang, Y., Wen, W., Whelan, C.D., Wittfeld, K., Wright, M., Yamamori, H., Zayats, T., Agartz, I., Westlye, L.T., Jacquemont, S., Djurovic, S., Stefánsson, H., Stefánsson, K., Thompson, P., and Andreassen, O.A.
Abstract: Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
Published: 2020

43. Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Author: Hofer, E, Roshchupkin, GV, Adams, HHH, Knol, MJ, Lin, H, Li, S, Zare, H, Ahmad, S, Armstrong, NJ, Satizabal, CL, Bernard, M, Bis, JC, Gillespie, NA, Luciano, M, Mishra, A, Scholz, M, Teumer, A, Xia, R, Jian, X, Mosley, TH, Saba, Y, Pirpamer, L, Seiler, S, Becker, JT, Carmichael, O, Rotter, JI, Psaty, BM, Lopez, OL, Amin, N, van der Lee, SJ, Yang, Q, Himali, JJ, Maillard, P, Beiser, AS, Decarli, C, Karama, S, Lewis, L, Harris, M, Bastin, ME, Deary, IJ, Witte, AV, Beyer, F, Loeffler, M, Mather, KA, Schofield, PR, Thalamuthu, A, Kwok, JB, Wright, MJ, Ames, D, Trollor, J, Jiang, J, Brodaty, H, Wen, W, Vernooij, MW, Hofman, A, Uitterlinden, AG, Niessen, WJ, Wittfeld, K, Bülow, R, Völker, U, Pausova, Z, Pike, GB, Maingault, S, Crivello, F, Tzourio, C, Amouyel, P, Mazoyer, B, Neale, MC, Franz, CE, Lyons, MJ, Panizzon, MS, Andreassen, OA, Dale, AM, Logue, M, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Stein, JL, Thompson, PM, Medland, SE, Sachdev, PS, Kremen, WS, Wardlaw, JM, Villringer, A, van Duijn, CM, Grabe, HJ, Longstreth, WT, Fornage, M, Paus, T, Debette, S, Ikram, MA, Schmidt, H, Schmidt, R, Seshadri, S, Ching, CRK, Hofer, E, Roshchupkin, GV, Adams, HHH, Knol, MJ, Lin, H, Li, S, Zare, H, Ahmad, S, Armstrong, NJ, Satizabal, CL, Bernard, M, Bis, JC, Gillespie, NA, Luciano, M, Mishra, A, Scholz, M, Teumer, A, Xia, R, Jian, X, Mosley, TH, Saba, Y, Pirpamer, L, Seiler, S, Becker, JT, Carmichael, O, Rotter, JI, Psaty, BM, Lopez, OL, Amin, N, van der Lee, SJ, Yang, Q, Himali, JJ, Maillard, P, Beiser, AS, Decarli, C, Karama, S, Lewis, L, Harris, M, Bastin, ME, Deary, IJ, Witte, AV, Beyer, F, Loeffler, M, Mather, KA, Schofield, PR, Thalamuthu, A, Kwok, JB, Wright, MJ, Ames, D, Trollor, J, Jiang, J, Brodaty, H, Wen, W, Vernooij, MW, Hofman, A, Uitterlinden, AG, Niessen, WJ, Wittfeld, K, Bülow, R, Völker, U, Pausova, Z, Pike, GB, Maingault, S, Crivello, F, Tzourio, C, Amouyel, P, Mazoyer, B, Neale, MC, Franz, CE, Lyons, MJ, Panizzon, MS, Andreassen, OA, Dale, AM, Logue, M, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Stein, JL, Thompson, PM, Medland, SE, Sachdev, PS, Kremen, WS, Wardlaw, JM, Villringer, A, van Duijn, CM, Grabe, HJ, Longstreth, WT, Fornage, M, Paus, T, Debette, S, Ikram, MA, Schmidt, H, Schmidt, R, Seshadri, S, and Ching, CRK
Abstract: Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
Published: 2020

44. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M, Suzuki, H, Jian, X, Sarnowski, C, Evans, TE, Bis, JC, Eiriksdottir, G, Sakaue, S, Terzikhan, N, Habes, M, Zhao, W, Armstrong, NJ, Hofer, E, Yanek, LR, Hagenaars, SP, Kumar, RB, van den Akker, EB, McWhirter, RE, Trompet, S, Mishra, A, Saba, Y, Satizabal, CL, Beaudet, G, Petit, L, Tsuchida, A, Zago, L, Schilling, S, Sigurdsson, S, Gottesman, RF, Lewis, CE, Aggarwal, NT, Lopez, OL, Smith, JA, Valdés Hernández, MC, van der Grond, J, Wright, MJ, Knol, MJ, Dörr, M, Thomson, RJ, Bordes, C, Le Grand, Q, Duperron, MG, Smith, AV, Knopman, DS, Schreiner, PJ, Evans, DA, Rotter, JI, Beiser, AS, Maniega, SM, Beekman, M, Trollor, J, Stott, DJ, Vernooij, MW, Wittfeld, K, Niessen, WJ, Soumaré, A, Boerwinkle, E, Sidney, S, Turner, ST, Davies, G, Thalamuthu, A, Völker, U, van Buchem, MA, Bryan, RN, Dupuis, J, Bastin, ME, Ames, D, Teumer, A, Amouyel, P, Kwok, JB, Bülow, R, Deary, IJ, Schofield, PR, Brodaty, H, Jiang, J, Tabara, Y, Setoh, K, Miyamoto, S, Yoshida, K, Nagata, M, Kamatani, Y, Matsuda, F, Psaty, BM, Bennett, DA, De Jager, PL, Mosley, TH, Sachdev, PS, Schmidt, R, Warren, HR, Evangelou, E, Trégouët, DA, de Andrade, M, Basu, S, Berr, C, Brody, JA, Chasman, DI, Dartigues, JF, Folsom, AR, Germain, M, Sargurupremraj, M, Suzuki, H, Jian, X, Sarnowski, C, Evans, TE, Bis, JC, Eiriksdottir, G, Sakaue, S, Terzikhan, N, Habes, M, Zhao, W, Armstrong, NJ, Hofer, E, Yanek, LR, Hagenaars, SP, Kumar, RB, van den Akker, EB, McWhirter, RE, Trompet, S, Mishra, A, Saba, Y, Satizabal, CL, Beaudet, G, Petit, L, Tsuchida, A, Zago, L, Schilling, S, Sigurdsson, S, Gottesman, RF, Lewis, CE, Aggarwal, NT, Lopez, OL, Smith, JA, Valdés Hernández, MC, van der Grond, J, Wright, MJ, Knol, MJ, Dörr, M, Thomson, RJ, Bordes, C, Le Grand, Q, Duperron, MG, Smith, AV, Knopman, DS, Schreiner, PJ, Evans, DA, Rotter, JI, Beiser, AS, Maniega, SM, Beekman, M, Trollor, J, Stott, DJ, Vernooij, MW, Wittfeld, K, Niessen, WJ, Soumaré, A, Boerwinkle, E, Sidney, S, Turner, ST, Davies, G, Thalamuthu, A, Völker, U, van Buchem, MA, Bryan, RN, Dupuis, J, Bastin, ME, Ames, D, Teumer, A, Amouyel, P, Kwok, JB, Bülow, R, Deary, IJ, Schofield, PR, Brodaty, H, Jiang, J, Tabara, Y, Setoh, K, Miyamoto, S, Yoshida, K, Nagata, M, Kamatani, Y, Matsuda, F, Psaty, BM, Bennett, DA, De Jager, PL, Mosley, TH, Sachdev, PS, Schmidt, R, Warren, HR, Evangelou, E, Trégouët, DA, de Andrade, M, Basu, S, Berr, C, Brody, JA, Chasman, DI, Dartigues, JF, Folsom, AR, and Germain, M
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Published: 2020

45. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

Author: Dima, D. (Danai), Modabbernia, A. (Amirhossein), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L., Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), van't Ent, D. (Dennis), Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Williams, S.C.R. (Steven C. R.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), Frangou, S. (Sophia), Dima, D. (Danai), Modabbernia, A. (Amirhossein), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L., Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), van't Ent, D. (Dennis), Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Williams, S.C.R. (Steven C. R.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), and Frangou, S. (Sophia)
Abstract: Age 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.
Published: 2020
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46. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. 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(Myriam), Debette, S. (Stéphanie), Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), and Debette, S. (Stéphanie)
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Published: 2020
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47. Global and regional development of the human cerebral cortex: Molecular architecture and occupational aptitudes

Author: Paus, T., Seshadri, S., Pausova, Z., Sestan, N., Jahanshad, N., Ding, L., Kremen, W.S., Franz, C.E., Gillespie, N.A., Debette, S., Maingault, S., Mishra, A., Tzourio, C., Grabe, H.J., Bülow, R., Wittfeld, K., van der -Palitschka, S., Frenzel, S., Ikram, M.A., Adams, H.H.H.H., Evans, T.E., Terzikhan, N., Sachdev, P.S., Wen, W., Brodaty, H., Wright, M.J., Trollor, J.N., Thalamuthu, A., Schofield, P.R., Kwok, J.B., Jiang, J., Ames, D., Mather, K.A., Armstrong, N.J., Villringer, A., Beyer, F., Witte, A.V., Loeffler, M., Scholz, M., Deary, I.E., Wardlaw, J.M., Harris, M.A., Bastin, M.E., Lewis, L., Karama, S., Luciano, M., Yang, Q., Li, S., Bis, J.C., Mazoyer, B., Crivello, F., Carrion-Castillo, A., Schmidt, H., Schmidt, R., Pirpamer, L., Saba, Y., Fornage, M., Mosley, T.H., Gottesman, R., Jian, X., Sousa, A.M.M., Roshchupkin, G.V., Tilley, S., Vosberg, D.E., Patel, Y., Hofer, E., Ma, S., Shin, J., Paus, T., Seshadri, S., Pausova, Z., Sestan, N., Jahanshad, N., Ding, L., Kremen, W.S., Franz, C.E., Gillespie, N.A., Debette, S., Maingault, S., Mishra, A., Tzourio, C., Grabe, H.J., Bülow, R., Wittfeld, K., van der -Palitschka, S., Frenzel, S., Ikram, M.A., Adams, H.H.H.H., Evans, T.E., Terzikhan, N., Sachdev, P.S., Wen, W., Brodaty, H., Wright, M.J., Trollor, J.N., Thalamuthu, A., Schofield, P.R., Kwok, J.B., Jiang, J., Ames, D., Mather, K.A., Armstrong, N.J., Villringer, A., Beyer, F., Witte, A.V., Loeffler, M., Scholz, M., Deary, I.E., Wardlaw, J.M., Harris, M.A., Bastin, M.E., Lewis, L., Karama, S., Luciano, M., Yang, Q., Li, S., Bis, J.C., Mazoyer, B., Crivello, F., Carrion-Castillo, A., Schmidt, H., Schmidt, R., Pirpamer, L., Saba, Y., Fornage, M., Mosley, T.H., Gottesman, R., Jian, X., Sousa, A.M.M., Roshchupkin, G.V., Tilley, S., Vosberg, D.E., Patel, Y., Hofer, E., Ma, S., and Shin, J.
Abstract: We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade—albeit in a very limited manner—to behaviors as complex as the choice of one’s occupation.
Published: 2020

48. The genetic architecture of the human cerebral cortex

Author: Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Ching, C.R.K., McMahon, M.A.B., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A.A., Alnæs, D., Amlien, I.K., Andersson, M., Ard, T., Armstrong, N.J., Ashley-Koch, A., Atkins, J.R., Bernard, M., Brouwer, R.M., Buimer, E.E.L., Bülow, R., Bürger, C., Cannon, D.M., Chakravarty, M.M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., de Araujo, T.K., de Zubicaray, G.I., de Zwarte, S.M.C., den Braber, A., Doan, N.T., Dohm, K., Ehrlich, S., Engelbrecht, H-R, Erk, S., Fan, C.C., Fedko, I.O., Foley, S.F., Ford, J.M., Fukunaga, M., Garrett, M.E., Ge, T., Giddaluru, S., Goldman, A.L., Green, M.J., Groenewold, N.A., Grotegerd, D., Gurholt, T.P., Gutman, B.A., Hansell, N.K., Harris, M.A., Harrison, M.B., Haswell, C.C., Hauser, M., Herms, S., Heslenfeld, D.J., Ho, N.F., Hoehn, D., Hoffmann, P., Holleran, L., Hoogman, M., Hottenga, J-J, Ikeda, M., Janowitz, D., Jansen, I.E., Jia, T., Jockwitz, C., Kanai, R., Karama, S., Kasperaviciute, D., Kaufmann, T., Kelly, S., Kikuchi, M., Klein, M., Knapp, M., Knodt, A.R., Krämer, B., Lam, M., Lancaster, T.M., Lee, P.H., Lett, T.A., Lewis, L.B., Lopes-Cendes, I., Luciano, M., Macciardi, F., Marquand, A.F., Mathias, S.R., Melzer, T.R., Milaneschi, Y., Mirza-Schreiber, N., Moreira, J.C.V., Mühleisen, T.W., Müller-Myhsok, B., Najt, P., Nakahara, S., Nho, K., Olde Loohuis, L.M., Orfanos, D.P., Pearson, J.F., Pitcher, T.L., Pütz, B., Quidé, Y., Ragothaman, A., Rashid, F.M., Reay, W.R., Redlich, R., Reinbold, C.S., Repple, J., Richard, G., Riedel, B.C., Risacher, S.L., Rocha, C.S., Mota, N.R., Salminen, L., Saremi, A., Saykin, A.J., Schlag, F., Schmaal, L., Schofield, P.R., Secolin, R., Shapland, C.Y., Shen, L., Shin, J., Shumskaya, E., Sønderby, I.E., Sprooten, E., Tansey, K.E., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.A., Uhlmann, A., Vallerga, C.L., van der Meer, D., van Donkelaar, M.M.J., van Eijk, L., Van Erp, T.G.M., van Haren, N.E.M., Van Rooij, D., van Tol, M-J, Veldink, J.H., Verhoef, E., Walton, E., Wang, M., Wang, Y., Wardlaw, J.M., Wen, W., Westlye, L.T., Whelan, C.D., Witt, S.H., Wittfeld, K., Wolf, C., Wolfers, T., Wu, J.Q., Yasuda, C.L., Zaremba, D., Zhang, Z., Zwiers, M.P., Artiges, E., Assareh, A.A., Ayesa-Arriola, R., Belger, A., Brandt, C.L., Brown, G.G., Cichon, S., Curran, J.E., Davies, G.E., Degenhardt, F., Dennis, M.F., Dietsche, B., Djurovic, S., Doherty, C.P., Espiritu, R., Garijo, D., Gil, Y., Gowland, P.A., Green, R.C., Häusler, A.N., Heindel, W., Ho, B-C., Hoffmann, W.U., Holsboer, F., Homuth, G., Hosten, N., Jack, C.R., Jang, M., Jansen, A., Kimbrel, N.A., Kolskår, K., Koops, S., Krug, A., Lim, K.O., Luykx, J.J., Mathalon, D.H., Mather, K.A., Mattay, V.S., Matthews, S., Mayoral Van Son, J., McEwen, S.C., Melle, I., Morris, D.W., Mueller, B.A., Nauck, M., Nordvik, J.E., Nöthen, M.M., O’Leary, D.S., Opel, N., Martinot, M-L.P., Pike, G.B., Preda, A., Quinlan, E.B., Rasser, P.E., Ratnakar, V., Reppermund, S., Steen, V.M., Tooney, P.A., Torres, F.R., Veltman, D.J., Voyvodic, J.T., Whelan, R., White, T., Yamamori, H., Adams, H.H.H., Bis, J.C., Debette, S., DeCarli, C., Fornage, M., Gudnason, V., Hofer, E., Ikram, M.A., Launer, L., Longstreth, W.T., Lopez, O.L., Mazoyer, B., Mosley, T.H., Roshchupkin, G.V., Satizabal, C.L., Schmidt, R., Seshadri, S., Yang, Q., Alvim, M.K.M., Ames, D., Anderson, T.J., Andreassen, O.A., Arias-Vasquez, A., Bastin, M.E., Baune, B.T., Beckham, J.C., Blangero, J., Boomsma, D.I., Brodaty, H., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bustillo, J.R., Cahn, W., Cairns, M.J., Calhoun, V., Carr, V.J., Caseras, X., Caspers, S., Cavalleri, G.L., Cendes, F., Corvin, A., Crespo-Facorro, B., Dalrymple-Alford, J.C., Dannlowski, U., de Geus, E.J.C., Deary, I.J., Delanty, N., Depondt, C., Desrivières, S., Donohoe, G., Espeseth, T., Fernández, G., Fisher, S.E., Flor, H., Forstner, A.J., Francks, C., Franke, B., Glahn, D.C., Gollub, R.L., Grabe, H.J., Gruber, O., Håberg, A.K., Hariri, A.R., Hartman, C.A., Hashimoto, R., Heinz, A., Henskens, F.A., Hillegers, M.H.J., Hoekstra, P.J., Holmes, A.J., Hong, L.E., Hopkins, W.D., Hulshoff Pol, H.E., Jernigan, T.L., Jönsson, E.G., Kahn, R.S., Kennedy, M.A., Kircher, T.T.J., Kochunov, P., Kwok, J.B.J., Le Hellard, S., Loughland, C.M., Martin, N.G., Martinot, J-L, McDonald, C., McMahon, K.L., Meyer-Lindenberg, A., Michie, P.T., Morey, R.A., Mowry, B., Nyberg, L., Oosterlaan, J., Ophoff, R.A., Pantelis, C., Paus, T., Pausova, Z., Penninx, B.W.J.H., Polderman, T.J.C., Posthuma, D., Rietschel, M., Roffman, J.L., Rowland, L.M., Sachdev, P.S., Sämann, P.G., Schall, U., Schumann, G., Scott, R.J., Sim, K., Sisodiya, S.M., Smoller, J.W., Sommer, I.E., St Pourcain, B., Stein, D.J., Toga, A.W., Trollor, J.N., van der Wee, N.J.A., van ’t Ent, D., Völzke, H., Walter, H., Weber, B., Weinberger, D.R., Wright, M.J., Zhou, J., Stein, J.L., Thompson, P.M., Medland, S.E., Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Ching, C.R.K., McMahon, M.A.B., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A.A., Alnæs, D., Amlien, I.K., Andersson, M., Ard, T., Armstrong, N.J., Ashley-Koch, A., Atkins, J.R., Bernard, M., Brouwer, R.M., Buimer, E.E.L., Bülow, R., Bürger, C., Cannon, D.M., Chakravarty, M.M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., de Araujo, T.K., de Zubicaray, G.I., de Zwarte, S.M.C., den Braber, A., Doan, N.T., Dohm, K., Ehrlich, S., Engelbrecht, H-R, Erk, S., Fan, C.C., Fedko, I.O., Foley, S.F., Ford, J.M., Fukunaga, M., Garrett, M.E., Ge, T., Giddaluru, S., Goldman, A.L., Green, M.J., Groenewold, N.A., Grotegerd, D., Gurholt, T.P., Gutman, B.A., Hansell, N.K., Harris, M.A., Harrison, M.B., Haswell, C.C., Hauser, M., Herms, S., Heslenfeld, D.J., Ho, N.F., Hoehn, D., Hoffmann, P., Holleran, L., Hoogman, M., Hottenga, J-J, Ikeda, M., Janowitz, D., Jansen, I.E., Jia, T., Jockwitz, C., Kanai, R., Karama, S., Kasperaviciute, D., Kaufmann, T., Kelly, S., Kikuchi, M., Klein, M., Knapp, M., Knodt, A.R., Krämer, B., Lam, M., Lancaster, T.M., Lee, P.H., Lett, T.A., Lewis, L.B., Lopes-Cendes, I., Luciano, M., Macciardi, F., Marquand, A.F., Mathias, S.R., Melzer, T.R., Milaneschi, Y., Mirza-Schreiber, N., Moreira, J.C.V., Mühleisen, T.W., Müller-Myhsok, B., Najt, P., Nakahara, S., Nho, K., Olde Loohuis, L.M., Orfanos, D.P., Pearson, J.F., Pitcher, T.L., Pütz, B., Quidé, Y., Ragothaman, A., Rashid, F.M., Reay, W.R., Redlich, R., Reinbold, C.S., Repple, J., Richard, G., Riedel, B.C., Risacher, S.L., Rocha, C.S., Mota, N.R., Salminen, L., Saremi, A., Saykin, A.J., Schlag, F., Schmaal, L., Schofield, P.R., Secolin, R., Shapland, C.Y., Shen, L., Shin, J., Shumskaya, E., Sønderby, I.E., Sprooten, E., Tansey, K.E., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.A., Uhlmann, A., Vallerga, C.L., van der Meer, D., van Donkelaar, M.M.J., van Eijk, L., Van Erp, T.G.M., van Haren, N.E.M., Van Rooij, D., van Tol, M-J, Veldink, J.H., Verhoef, E., Walton, E., Wang, M., Wang, Y., Wardlaw, J.M., Wen, W., Westlye, L.T., Whelan, C.D., Witt, S.H., Wittfeld, K., Wolf, C., Wolfers, T., Wu, J.Q., Yasuda, C.L., Zaremba, D., Zhang, Z., Zwiers, M.P., Artiges, E., Assareh, A.A., Ayesa-Arriola, R., Belger, A., Brandt, C.L., Brown, G.G., Cichon, S., Curran, J.E., Davies, G.E., Degenhardt, F., Dennis, M.F., Dietsche, B., Djurovic, S., Doherty, C.P., Espiritu, R., Garijo, D., Gil, Y., Gowland, P.A., Green, R.C., Häusler, A.N., Heindel, W., Ho, B-C., Hoffmann, W.U., Holsboer, F., Homuth, G., Hosten, N., Jack, C.R., Jang, M., Jansen, A., Kimbrel, N.A., Kolskår, K., Koops, S., Krug, A., Lim, K.O., Luykx, J.J., Mathalon, D.H., Mather, K.A., Mattay, V.S., Matthews, S., Mayoral Van Son, J., McEwen, S.C., Melle, I., Morris, D.W., Mueller, B.A., Nauck, M., Nordvik, J.E., Nöthen, M.M., O’Leary, D.S., Opel, N., Martinot, M-L.P., Pike, G.B., Preda, A., Quinlan, E.B., Rasser, P.E., Ratnakar, V., Reppermund, S., Steen, V.M., Tooney, P.A., Torres, F.R., Veltman, D.J., Voyvodic, J.T., Whelan, R., White, T., Yamamori, H., Adams, H.H.H., Bis, J.C., Debette, S., DeCarli, C., Fornage, M., Gudnason, V., Hofer, E., Ikram, M.A., Launer, L., Longstreth, W.T., Lopez, O.L., Mazoyer, B., Mosley, T.H., Roshchupkin, G.V., Satizabal, C.L., Schmidt, R., Seshadri, S., Yang, Q., Alvim, M.K.M., Ames, D., Anderson, T.J., Andreassen, O.A., Arias-Vasquez, A., Bastin, M.E., Baune, B.T., Beckham, J.C., Blangero, J., Boomsma, D.I., Brodaty, H., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bustillo, J.R., Cahn, W., Cairns, M.J., Calhoun, V., Carr, V.J., Caseras, X., Caspers, S., Cavalleri, G.L., Cendes, F., Corvin, A., Crespo-Facorro, B., Dalrymple-Alford, J.C., Dannlowski, U., de Geus, E.J.C., Deary, I.J., Delanty, N., Depondt, C., Desrivières, S., Donohoe, G., Espeseth, T., Fernández, G., Fisher, S.E., Flor, H., Forstner, A.J., Francks, C., Franke, B., Glahn, D.C., Gollub, R.L., Grabe, H.J., Gruber, O., Håberg, A.K., Hariri, A.R., Hartman, C.A., Hashimoto, R., Heinz, A., Henskens, F.A., Hillegers, M.H.J., Hoekstra, P.J., Holmes, A.J., Hong, L.E., Hopkins, W.D., Hulshoff Pol, H.E., Jernigan, T.L., Jönsson, E.G., Kahn, R.S., Kennedy, M.A., Kircher, T.T.J., Kochunov, P., Kwok, J.B.J., Le Hellard, S., Loughland, C.M., Martin, N.G., Martinot, J-L, McDonald, C., McMahon, K.L., Meyer-Lindenberg, A., Michie, P.T., Morey, R.A., Mowry, B., Nyberg, L., Oosterlaan, J., Ophoff, R.A., Pantelis, C., Paus, T., Pausova, Z., Penninx, B.W.J.H., Polderman, T.J.C., Posthuma, D., Rietschel, M., Roffman, J.L., Rowland, L.M., Sachdev, P.S., Sämann, P.G., Schall, U., Schumann, G., Scott, R.J., Sim, K., Sisodiya, S.M., Smoller, J.W., Sommer, I.E., St Pourcain, B., Stein, D.J., Toga, A.W., Trollor, J.N., van der Wee, N.J.A., van ’t Ent, D., Völzke, H., Walter, H., Weber, B., Weinberger, D.R., Wright, M.J., Zhou, J., Stein, J.L., Thompson, P.M., and Medland, S.E.
Abstract: INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When co
Published: 2020

49. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

Author: Thompson, P.M. (Paul), Jahanshad, N. (Neda), Ching, C.R.K. (Christopher), Salminen, L.E. (Lauren E.), Thomopoulos, S.I. (Sophia I.), Bright, J. (Joanna), Baune, B.T., Bertolín, S. (Sara), Bralten, L.B.C. (Linda), Bruin, W.B. (Willem B.), Bülow, R. (Robin), Chen, J. (Jian), Chye, Y. (Yann), Dannlowski, U. (Udo), de Kovel, C.G.F. (Carolien G F), Donohoe, D.J. (Dennis), Eyler, L.T. (Lisa T.), Faraone, S.V. (Stephen), Favre, P. (Pauline), Filippi, C.A. (Courtney A.), Frodl, T. (Thomas), Garijo, D. (Daniel), Gil, Y. (Yolanda), Grabe, H.J. (Hans Jörgen), Grasby, K.L. (Katrina L.), Hajek, T. (Tomas), Han, L.K.M. (Laura K M), Hatton, W., Hilbert, K. (Kevin), Ho, T.C. (Tiffany C.), Holleran, L. (Laurena), Homuth, G. (Georg), Hosten, N. (Norbert), Houenou, J. (Josselin), Ivanov, I. (Iliyan), Jia, T. (Tianye), Kelly, S. (Sinead), Klein, M. (Marieke), Kwon, J.S. (Jun Soo), Laansma, M.A. (Max A.), Leerssen, J. (Jeanne), Lueken, U. (Ulrike), Nunes, A. (Abraham), Neill, J.O. (Joseph O'), Opel, N. (Nils), Piras, F. (Fabrizio), Piras, F. (Federica), Postema, M.C. (Merel C.), Pozzi, E. (Elena), Shatokhina, N. (Natalia), Soriano-Mas, C. (Carles), Spalletta, G. (Gianfranco), Sun, D. (Daqiang), Teumer, A. (Alexander), Tilot, A.K. (Amanda K.), Tozzi, L. (Leonardo), van der Merwe, C. (Celia), Someren, E.J.W. (Eus) van, van Wingen, G.A. (Guido A.), Völzke, H. (Henry), Walton, E. (Esther), Wang, L. (Lei), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Wright, M.J. (Margaret), Yun, J.-Y. (Je-Yeon), Zhang, G. (Guohao), Zhang-James, Y. (Yanli), Adhikari, B.M. (Bhim M.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Aleman, A. (André), Althoff, R.R. (Robert R.), Altmann, A. (A.), Andreassen, O.A. (Ole), Baron, D.A. (David A.), Bartnik-Olson, B.L. (Brenda L.), Marie Bas-Hoogendam, J. (Janna), Baskin-Sommers, A.R. (Arielle R.), Bearden, C.E. (Carrie), Berner, L.A. (Laura A.), Boedhoe, P.S.W. (Premika S W), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan), Caeyenberghs, K. (Karen), Cecil, C.A.M. (Charlotte), Cohen, R.A. (Ronald A.), Cole, J.H. (James H.), Conrod, P. (Patricia), De Brito, S.A. (Stephane A.), de Zwarte, S.M.C. (Sonja M C), Dennis, E.L. (Emily L.), Desrivieres, S. (Sylvane), Dima, D. (Danai), Ehrlich, S.M. (Stefan), Esopenko, C. (Carrie), Fairchild, G. (Graeme), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Francks, C. (Clyde), Frangou, S. (Sophia), Franke, B. (Barbara), Garavan, H.P. (Hugh P.), Glahn, D.C. (David), Groenewold, N.A. (Nynke A.), Gurholt, T.P. (Tiril P.), Gutman, B.A. (Boris A.), Hahn, T. (Tim), Harding, I.H. (Ian H.), Hernaus, D. (Dennis), Hibar, D.P. (Derrek P.), Hillary, F.G. (Frank G.), Hoogman, M. (Martine), Hulshoff Pol, H.E. (Hilleke E.), Jalbrzikowski, M. (Maria), Karkashadze, G.A. (George A.), Klapwijk, E.T. (Eduard T.), Knickmeyer, R.C. (Rebecca C.), Kochunov, P. (Peter), Koerte, I.K. (Inga K.), Kong, X.-Z. (Xiang-Zhen), Liew, S.-L. (Sook-Lei), Lin, A.P. (Alexander P.), Logue, M.W. (Mark W.), Luders, E. (Eileen), Macciardi, F. (Fabio), Mackey, S. (Scott), Mayer, A.R. (Andrew R.), McDonald, C.R. (Carrie R.), McMahon, A.B. (Agnes B.), Medland, S.E. (Sarah), Modinos, G. (Gemma), Morey, R.A. (Rajendra A.), Mueller, S.C. (Sven C.), Mukherjee, P. (Pratik), Namazova-Baranova, L. (L.), Nir, T.M. (Talia M.), Olsen, A. (Alexander), Paschou, P. (Peristera), Pine, D.S. (Daniel S.), Pizzagalli, F. (Fabrizio), Rentería, M.E. (Miguel), Rohrer, J.D. (Jonathan D.), Sämann, P.G. (Philipp), Schmaal, L. (Lianne), Schumann, G. (Gunter), Shiroishi, M.S. (Mark S.), Sisodiya, S.M. (Sanjay), Smit, D.J.A. (Dirk J A), Sønderby, I.E. (Ida E.), Stein, D.J. (Dan J.), Stein, J.L., Tahmasian, M. (Masoud), Tate, D.F. (David F.), Turner, J. (Jessica), Heuvel, O.A. (Odile A.), Wee, N.J. (Nic) van der, van der Werf, Y.D. (Ysbrand), Erp, T.G.M. (Theo G.) van, van Haren, N.E.M. (Neeltje E M), van Rooij, D. (Daan), Van Velzen, L.S., Veer, I.M. (Ilya), Veltman, D.J. (Dick), Villalon-Reina, J.E. (Julio E.), Walter, H.J. (Henrik), Whelan, C.D. (Christopher), Wilde, E.A. (Elisabeth A.), Zarei, M. (Mojtaba), Zelman, V. (Vladimir), Thompson, P.M. (Paul), Jahanshad, N. (Neda), Ching, C.R.K. (Christopher), Salminen, L.E. (Lauren E.), Thomopoulos, S.I. (Sophia I.), Bright, J. (Joanna), Baune, B.T., Bertolín, S. (Sara), Bralten, L.B.C. (Linda), Bruin, W.B. (Willem B.), Bülow, R. (Robin), Chen, J. (Jian), Chye, Y. (Yann), Dannlowski, U. (Udo), de Kovel, C.G.F. (Carolien G F), Donohoe, D.J. (Dennis), Eyler, L.T. (Lisa T.), Faraone, S.V. (Stephen), Favre, P. (Pauline), Filippi, C.A. (Courtney A.), Frodl, T. (Thomas), Garijo, D. (Daniel), Gil, Y. (Yolanda), Grabe, H.J. (Hans Jörgen), Grasby, K.L. (Katrina L.), Hajek, T. (Tomas), Han, L.K.M. (Laura K M), Hatton, W., Hilbert, K. (Kevin), Ho, T.C. (Tiffany C.), Holleran, L. (Laurena), Homuth, G. (Georg), Hosten, N. (Norbert), Houenou, J. (Josselin), Ivanov, I. (Iliyan), Jia, T. (Tianye), Kelly, S. (Sinead), Klein, M. (Marieke), Kwon, J.S. (Jun Soo), Laansma, M.A. (Max A.), Leerssen, J. (Jeanne), Lueken, U. (Ulrike), Nunes, A. (Abraham), Neill, J.O. (Joseph O'), Opel, N. (Nils), Piras, F. (Fabrizio), Piras, F. (Federica), Postema, M.C. (Merel C.), Pozzi, E. (Elena), Shatokhina, N. (Natalia), Soriano-Mas, C. (Carles), Spalletta, G. (Gianfranco), Sun, D. (Daqiang), Teumer, A. (Alexander), Tilot, A.K. (Amanda K.), Tozzi, L. (Leonardo), van der Merwe, C. (Celia), Someren, E.J.W. (Eus) van, van Wingen, G.A. (Guido A.), Völzke, H. (Henry), Walton, E. (Esther), Wang, L. (Lei), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Wright, M.J. (Margaret), Yun, J.-Y. (Je-Yeon), Zhang, G. (Guohao), Zhang-James, Y. (Yanli), Adhikari, B.M. (Bhim M.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Aleman, A. (André), Althoff, R.R. (Robert R.), Altmann, A. (A.), Andreassen, O.A. (Ole), Baron, D.A. (David A.), Bartnik-Olson, B.L. (Brenda L.), Marie Bas-Hoogendam, J. (Janna), Baskin-Sommers, A.R. (Arielle R.), Bearden, C.E. (Carrie), Berner, L.A. (Laura A.), Boedhoe, P.S.W. (Premika S W), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan), Caeyenberghs, K. (Karen), Cecil, C.A.M. (Charlotte), Cohen, R.A. (Ronald A.), Cole, J.H. (James H.), Conrod, P. (Patricia), De Brito, S.A. (Stephane A.), de Zwarte, S.M.C. (Sonja M C), Dennis, E.L. (Emily L.), Desrivieres, S. (Sylvane), Dima, D. (Danai), Ehrlich, S.M. (Stefan), Esopenko, C. (Carrie), Fairchild, G. (Graeme), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Francks, C. (Clyde), Frangou, S. (Sophia), Franke, B. (Barbara), Garavan, H.P. (Hugh P.), Glahn, D.C. (David), Groenewold, N.A. (Nynke A.), Gurholt, T.P. (Tiril P.), Gutman, B.A. (Boris A.), Hahn, T. (Tim), Harding, I.H. (Ian H.), Hernaus, D. (Dennis), Hibar, D.P. (Derrek P.), Hillary, F.G. (Frank G.), Hoogman, M. (Martine), Hulshoff Pol, H.E. (Hilleke E.), Jalbrzikowski, M. (Maria), Karkashadze, G.A. (George A.), Klapwijk, E.T. (Eduard T.), Knickmeyer, R.C. (Rebecca C.), Kochunov, P. (Peter), Koerte, I.K. (Inga K.), Kong, X.-Z. (Xiang-Zhen), Liew, S.-L. (Sook-Lei), Lin, A.P. (Alexander P.), Logue, M.W. (Mark W.), Luders, E. (Eileen), Macciardi, F. (Fabio), Mackey, S. (Scott), Mayer, A.R. (Andrew R.), McDonald, C.R. (Carrie R.), McMahon, A.B. (Agnes B.), Medland, S.E. (Sarah), Modinos, G. (Gemma), Morey, R.A. (Rajendra A.), Mueller, S.C. (Sven C.), Mukherjee, P. (Pratik), Namazova-Baranova, L. (L.), Nir, T.M. (Talia M.), Olsen, A. (Alexander), Paschou, P. (Peristera), Pine, D.S. (Daniel S.), Pizzagalli, F. (Fabrizio), Rentería, M.E. (Miguel), Rohrer, J.D. (Jonathan D.), Sämann, P.G. (Philipp), Schmaal, L. (Lianne), Schumann, G. (Gunter), Shiroishi, M.S. (Mark S.), Sisodiya, S.M. (Sanjay), Smit, D.J.A. (Dirk J A), Sønderby, I.E. (Ida E.), Stein, D.J. (Dan J.), Stein, J.L., Tahmasian, M. (Masoud), Tate, D.F. (David F.), Turner, J. (Jessica), Heuvel, O.A. (Odile A.), Wee, N.J. (Nic) van der, van der Werf, Y.D. (Ysbrand), Erp, T.G.M. (Theo G.) van, van Haren, N.E.M. (Neeltje E M), van Rooij, D. (Daan), Van Velzen, L.S., Veer, I.M. (Ilya), Veltman, D.J. (Dick), Villalon-Reina, J.E. (Julio E.), Walter, H.J. (Henrik), Whelan, C.D. (Christopher), Wilde, E.A. (Elisabeth A.), Zarei, M. (Mojtaba), and Zelman, V. (Vladimir)
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
Published: 2020
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50. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

Author: Thompson, PM, Jahanshad, N, Ching, CRK, Salminen, LE, Thomopoulos, SI, Bright, J, Baune, BT, Bertolin, S, Bralten, J, Bruin, WB, Buelow, R, Chen, J, Chye, Y, Dannlowski, U, de Kovel, CGF, Donohoe, G, Eyler, LT, Faraone, SV, Favre, P, Filippi, CA, Frodl, T, Garijo, D, Gil, Y, Grabe, HJ, Grasby, KL, Hajek, T, Han, LKM, Hatton, SN, Hilbert, K, Ho, TC, Holleran, L, Homuth, G, Hosten, N, Houenou, J, Ivanov, I, Jia, T, Kelly, S, Klein, M, Kwon, JS, Laansma, MA, Leerssen, J, Lueken, U, Nunes, A, Neill, JO, Opel, N, Piras, F, Postema, MC, Pozzi, E, Shatokhina, N, Soriano-Mas, C, Spalletta, G, Sun, D, Teumer, A, Tilot, AK, Tozzi, L, van der Merwe, C, Van Someren, EJW, van Wingen, GA, Voelzke, H, Walton, E, Wang, L, Winkler, AM, Wittfeld, K, Wright, MJ, Yun, J-Y, Zhang, G, Zhang-James, Y, Adhikari, BM, Agartz, I, Aghajani, M, Aleman, A, Althoff, RR, Altmann, A, Andreassen, OA, Baron, DA, Bartnik-Olson, BL, Bas-Hoogendam, J, Baskin-Sommers, AR, Bearden, CE, Berner, LA, Boedhoe, PSW, Brouwer, RM, Buitelaar, JK, Caeyenberghs, K, Cecil, CAM, Cohen, RA, Cole, JH, Conrod, PJ, De Brito, SA, de Zwarte, SMC, Dennis, EL, Desrivieres, S, Dima, D, Ehrlich, S, Esopenko, C, Fairchild, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Garavan, HP, Glahn, DC, Groenewold, NA, Gurholt, TP, Gutman, BA, Hahn, T, Harding, IH, Hernaus, D, Hibar, DP, Hillary, FG, Hoogman, M, Pol, HE, Jalbrzikowski, M, Karkashadze, GA, Klapwijk, ET, Knickmeyer, RC, Kochunov, P, Koerte, IK, Kong, X-Z, Liew, S-L, Lin, AP, Logue, MW, Luders, E, Macciardi, F, Mackey, S, Mayer, AR, McDonald, CR, McMahon, AB, Medland, SE, Modinos, G, Morey, RA, Mueller, SC, Mukherjee, P, Namazova-Baranova, L, Nir, TM, Olsen, A, Paschou, P, Pine, DS, Pizzagalli, F, Renteria, ME, Rohrer, JD, Saemann, PG, Schmaal, L, Schumann, G, Shiroishi, MS, Sisodiya, SM, Smit, DJA, Sonderby, IE, Stein, DJ, Stein, JL, Tahmasian, M, Tate, DF, Turner, JA, van den Heuvel, OA, van der Wee, NJA, van der Werf, YD, van Erp, TGM, van Haren, NEM, van Rooij, D, van Velzen, LS, Veer, IM, Veltman, DJ, Villalon-Reina, JE, Walter, H, Whelan, CD, Wilde, EA, Zarei, M, Zelman, V, Thompson, PM, Jahanshad, N, Ching, CRK, Salminen, LE, Thomopoulos, SI, Bright, J, Baune, BT, Bertolin, S, Bralten, J, Bruin, WB, Buelow, R, Chen, J, Chye, Y, Dannlowski, U, de Kovel, CGF, Donohoe, G, Eyler, LT, Faraone, SV, Favre, P, Filippi, CA, Frodl, T, Garijo, D, Gil, Y, Grabe, HJ, Grasby, KL, Hajek, T, Han, LKM, Hatton, SN, Hilbert, K, Ho, TC, Holleran, L, Homuth, G, Hosten, N, Houenou, J, Ivanov, I, Jia, T, Kelly, S, Klein, M, Kwon, JS, Laansma, MA, Leerssen, J, Lueken, U, Nunes, A, Neill, JO, Opel, N, Piras, F, Postema, MC, Pozzi, E, Shatokhina, N, Soriano-Mas, C, Spalletta, G, Sun, D, Teumer, A, Tilot, AK, Tozzi, L, van der Merwe, C, Van Someren, EJW, van Wingen, GA, Voelzke, H, Walton, E, Wang, L, Winkler, AM, Wittfeld, K, Wright, MJ, Yun, J-Y, Zhang, G, Zhang-James, Y, Adhikari, BM, Agartz, I, Aghajani, M, Aleman, A, Althoff, RR, Altmann, A, Andreassen, OA, Baron, DA, Bartnik-Olson, BL, Bas-Hoogendam, J, Baskin-Sommers, AR, Bearden, CE, Berner, LA, Boedhoe, PSW, Brouwer, RM, Buitelaar, JK, Caeyenberghs, K, Cecil, CAM, Cohen, RA, Cole, JH, Conrod, PJ, De Brito, SA, de Zwarte, SMC, Dennis, EL, Desrivieres, S, Dima, D, Ehrlich, S, Esopenko, C, Fairchild, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Garavan, HP, Glahn, DC, Groenewold, NA, Gurholt, TP, Gutman, BA, Hahn, T, Harding, IH, Hernaus, D, Hibar, DP, Hillary, FG, Hoogman, M, Pol, HE, Jalbrzikowski, M, Karkashadze, GA, Klapwijk, ET, Knickmeyer, RC, Kochunov, P, Koerte, IK, Kong, X-Z, Liew, S-L, Lin, AP, Logue, MW, Luders, E, Macciardi, F, Mackey, S, Mayer, AR, McDonald, CR, McMahon, AB, Medland, SE, Modinos, G, Morey, RA, Mueller, SC, Mukherjee, P, Namazova-Baranova, L, Nir, TM, Olsen, A, Paschou, P, Pine, DS, Pizzagalli, F, Renteria, ME, Rohrer, JD, Saemann, PG, Schmaal, L, Schumann, G, Shiroishi, MS, Sisodiya, SM, Smit, DJA, Sonderby, IE, Stein, DJ, Stein, JL, Tahmasian, M, Tate, DF, Turner, JA, van den Heuvel, OA, van der Wee, NJA, van der Werf, YD, van Erp, TGM, van Haren, NEM, van Rooij, D, van Velzen, LS, Veer, IM, Veltman, DJ, Villalon-Reina, JE, Walter, H, Whelan, CD, Wilde, EA, Zarei, M, and Zelman, V
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
Published: 2020

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