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110 results on '"Alhusaini S"'

1. Genetic variants for head size share genes and pathways with cancer

Author: Knol, MJ, Poot, RA, Evans, TE, Satizabal, CL, Mishra, A, Sargurupremraj, M, van der Auwera, S, Duperron, MG, Jian, X, Hostettler, IC, van Dam-Nolen, DHK, Lamballais, S, Pawlak, MA, Lewis, CE, Carrion-Castillo, A, van Erp, TGM, Reinbold, CS, Shin, J, Scholz, M, Håberg, AK, Kämpe, A, Li, GHY, Avinun, R, Atkins, JR, Hsu, FC, Amod, AR, Lam, M, Tsuchida, A, Teunissen, MWA, Aygün, N, Patel, Y, Liang, D, Beiser, AS, Beyer, F, Bis, JC, Bos, D, Bryan, RN, Bülow, R, Caspers, S, Catheline, G, Cecil, CAM, Dalvie, S, Dartigues, JF, DeCarli, C, Enlund-Cerullo, M, Ford, JM, Franke, B, Freedman, BI, Friedrich, N, Green, MJ ; https://orcid.org/0000-0002-9361-4874, Haworth, S, Helmer, C, Hoffmann, P, Homuth, G, Ikram, MK, Jack, CR, Jahanshad, N, Jockwitz, C, Kamatani, Y, Knodt, AR, Li, S, Lim, K, Longstreth, WT, Macciardi, F, Amouyel, P, Arfanakis, K, Aribisala, BS, Bastin, ME, Chauhan, G, Chen, C, Cheng, CY, de Jager, PL, Deary, IJ, Fleischman, DA, Gottesman, RF, Gudnason, V, Hilal, S, Hofer, E, Janowitz, D, Jukema, JW, Liewald, DCM, Lopez, LM, Lopez, O, Luciano, M, Martinez, O, Niessen, WJ, Nyquist, P, Rotter, JI, Rundek, T, Sacco, RL, Schmidt, H, Tiemeier, H, Trompet, S, van der Grond, J, Völzke, H, Wardlaw, JM, Yanek, L, Yang, J, Agartz, I, Alhusaini, S, Quide, Yann ; https://orcid.org/0000-0002-8569-7139, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, Carr, Vaughan ; https://orcid.org/0000-0002-8907-5804, Brodaty, Henry ; https://orcid.org/0000-0001-9487-6617, Wen, Wei ; https://orcid.org/0000-0003-2753-3870, Knol, MJ, Poot, RA, Evans, TE, Satizabal, CL, Mishra, A, Sargurupremraj, M, van der Auwera, S, Duperron, MG, Jian, X, Hostettler, IC, van Dam-Nolen, DHK, Lamballais, S, Pawlak, MA, Lewis, CE, Carrion-Castillo, A, van Erp, TGM, Reinbold, CS, Shin, J, Scholz, M, Håberg, AK, Kämpe, A, Li, GHY, Avinun, R, Atkins, JR, Hsu, FC, Amod, AR, Lam, M, Tsuchida, A, Teunissen, MWA, Aygün, N, Patel, Y, Liang, D, Beiser, AS, Beyer, F, Bis, JC, Bos, D, Bryan, RN, Bülow, R, Caspers, S, Catheline, G, Cecil, CAM, Dalvie, S, Dartigues, JF, DeCarli, C, Enlund-Cerullo, M, Ford, JM, Franke, B, Freedman, BI, Friedrich, N, Green, MJ ; https://orcid.org/0000-0002-9361-4874, Haworth, S, Helmer, C, Hoffmann, P, Homuth, G, Ikram, MK, Jack, CR, Jahanshad, N, Jockwitz, C, Kamatani, Y, Knodt, AR, Li, S, Lim, K, Longstreth, WT, Macciardi, F, Amouyel, P, Arfanakis, K, Aribisala, BS, Bastin, ME, Chauhan, G, Chen, C, Cheng, CY, de Jager, PL, Deary, IJ, Fleischman, DA, Gottesman, RF, Gudnason, V, Hilal, S, Hofer, E, Janowitz, D, Jukema, JW, Liewald, DCM, Lopez, LM, Lopez, O, Luciano, M, Martinez, O, Niessen, WJ, Nyquist, P, Rotter, JI, Rundek, T, Sacco, RL, Schmidt, H, Tiemeier, H, Trompet, S, van der Grond, J, Völzke, H, Wardlaw, JM, Yanek, L, Yang, J, Agartz, I, Alhusaini, S, Quide, Yann ; https://orcid.org/0000-0002-8569-7139, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, Carr, Vaughan ; https://orcid.org/0000-0002-8907-5804, Brodaty, Henry ; https://orcid.org/0000-0001-9487-6617, and Wen, Wei ; https://orcid.org/0000-0003-2753-3870
Abstract: The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.
Published: 2024

2. Reproducibility in the absence of selective reporting: An illustration from large-scale brain asymmetry research

Author: Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, del Carmen Valdés Hernández, M, Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, and del Carmen Valdés Hernández, M
Published: 2022

3. Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Author: Park, B.-y., Larivière, S., Rodríguez-Cruces, R., Royer, J., Tavakol, S., Wang, Y., Caciagli, L., Caligiuri, M.E., Gambardella, A., Concha, L., Keller, S.S., Cendes, F., Alvim, M.K.M., Yasuda, C., Bonilha, L., Gleichgerrcht, E., Focke, N.K., Kreilkamp, B.A.K., Domin, M., Podewils, F. von, Langner, S., Rummel, C., Rebsamen, M., Wiest, R., Martin, P., Kotikalapudi, R., Bender, B., O’Brien, T.J., Law, M., Sinclair, B., Vivash, L., Kwan, P., Desmond, P.M., Malpas, C.B., Lui, E., Alhusaini, S., Doherty, C.P., Cavalleri, G.L., Delanty, N., Kälviäinen, R., Jackson, G.D., Kowalczyk, M., Mascalchi, M., Semmelroch, M., Thomas, R.H., Soltanian-Zadeh, H., Davoodi-Bojd, E., Zhang, J., Lenge, M., Guerrini, R., Bartolini, E., Hamandi, K., Foley, S., Weber, B., Depondt, C., Absil, J., Carr, S.J.A., Abela, E., Richardson, M.P., Devinsky, O., Severino, M., Striano, P., Parodi, C., Tortora, D., Hatton, S.N., Vos, S.B., Duncan, J.S., Galovic, M., Whelan, C.D., Bargalló, N., Pariente, J., Conde-Blanco, E., Vaudano, A.E., Tondelli, M., Meletti, S., Kong, X.Z., Francks, C., Fisher, S.E., Caldairou, B., Ryten, M., Labate, A., Sisodiya, S.M., Thompson, P.M., McDonald, C.R., Bernasconi, A., Bernasconi, N., Bernhardt, B.C., Park, B.-y., Larivière, S., Rodríguez-Cruces, R., Royer, J., Tavakol, S., Wang, Y., Caciagli, L., Caligiuri, M.E., Gambardella, A., Concha, L., Keller, S.S., Cendes, F., Alvim, M.K.M., Yasuda, C., Bonilha, L., Gleichgerrcht, E., Focke, N.K., Kreilkamp, B.A.K., Domin, M., Podewils, F. von, Langner, S., Rummel, C., Rebsamen, M., Wiest, R., Martin, P., Kotikalapudi, R., Bender, B., O’Brien, T.J., Law, M., Sinclair, B., Vivash, L., Kwan, P., Desmond, P.M., Malpas, C.B., Lui, E., Alhusaini, S., Doherty, C.P., Cavalleri, G.L., Delanty, N., Kälviäinen, R., Jackson, G.D., Kowalczyk, M., Mascalchi, M., Semmelroch, M., Thomas, R.H., Soltanian-Zadeh, H., Davoodi-Bojd, E., Zhang, J., Lenge, M., Guerrini, R., Bartolini, E., Hamandi, K., Foley, S., Weber, B., Depondt, C., Absil, J., Carr, S.J.A., Abela, E., Richardson, M.P., Devinsky, O., Severino, M., Striano, P., Parodi, C., Tortora, D., Hatton, S.N., Vos, S.B., Duncan, J.S., Galovic, M., Whelan, C.D., Bargalló, N., Pariente, J., Conde-Blanco, E., Vaudano, A.E., Tondelli, M., Meletti, S., Kong, X.Z., Francks, C., Fisher, S.E., Caldairou, B., Ryten, M., Labate, A., Sisodiya, S.M., Thompson, P.M., McDonald, C.R., Bernasconi, A., Bernasconi, N., and Bernhardt, B.C.
Abstract: Contains fulltext : 252489.pdf (Publisher’s version ) (Open Access)
Published: 2022

4. Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Author: Park, B-Y, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Tavakol, S, Wang, Y, Caciagli, L, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Alvim, MKM, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Kreilkamp, BAK, Domin, M, von Podewils, F, Langner, S, Rummel, C, Rebsamen, M, Wiest, R, Martin, P, Kotikalapudi, R, Bender, B, O'Brien, TJ, Law, M, Sinclair, B, Vivash, L, Kwan, P, Desmond, PM, Malpas, CB, Lui, E, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Parodi, C, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Galovic, M, Whelan, CD, Bargallo, N, Pariente, J, Conde-Blanco, E, Vaudano, AE, Tondelli, M, Meletti, S, Kong, X-Z, Francks, C, Fisher, SE, Caldairou, B, Ryten, M, Labate, A, Sisodiya, SM, Thompson, PM, McDonald, CR, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Park, B-Y, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Tavakol, S, Wang, Y, Caciagli, L, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Alvim, MKM, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Kreilkamp, BAK, Domin, M, von Podewils, F, Langner, S, Rummel, C, Rebsamen, M, Wiest, R, Martin, P, Kotikalapudi, R, Bender, B, O'Brien, TJ, Law, M, Sinclair, B, Vivash, L, Kwan, P, Desmond, PM, Malpas, CB, Lui, E, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Parodi, C, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Galovic, M, Whelan, CD, Bargallo, N, Pariente, J, Conde-Blanco, E, Vaudano, AE, Tondelli, M, Meletti, S, Kong, X-Z, Francks, C, Fisher, SE, Caldairou, B, Ryten, M, Labate, A, Sisodiya, SM, Thompson, PM, McDonald, CR, Bernasconi, A, Bernasconi, N, and Bernhardt, BC
Abstract: Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine ou
Published: 2022

5. A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies

Author: Altmann, A, Ryten, M, Di Nunzio, M, Ravizza, T, Tolomeo, D, Reynolds, RH, Somani, A, Bacigaluppi, M, Iori, V, Micotti, E, Di Sapia, R, Cerovic, M, Palma, E, Ruffolo, G, Botia, JA, Absil, J, Alhusaini, S, Alvim, MKM, Auvinen, P, Bargallo, N, Bartolini, E, Bender, B, Bergo, FPG, Bernardes, T, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Blackmon, K, Braga, B, Caligiuri, ME, Calvo, A, Carlson, C, Carr, SJA, Cavalleri, GL, Cendes, F, Chen, J, Chen, S, Cherubini, A, Concha, L, David, P, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP, Domin, M, Focke, NK, Foley, S, Franca, W, Gambardella, A, Guerrini, R, Hamandi, K, Hibar, DP, Isaev, D, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kowalczyk, MA, Kuzniecky, R, Kwan, P, Labate, A, Langner, S, Lenge, M, Liu, M, Martin, P, Mascalchi, M, Meletti, S, Morita-Sherman, ME, O'Brien, TJ, Pariente, JC, Richardson, MP, Rodriguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, MK, Severino, M, Striano, P, Thesen, T, Thomas, RH, Tondelli, M, Tortora, D, Vaudano, AE, Vivash, L, Podewils, F, Wagner, J, Weber, B, Wiest, R, Yasuda, CL, Zhang, G, Zhang, J, Leu, C, Avbersek, A, Thom, M, Whelan, CD, Thompson, P, McDonald, CR, Vezzani, A, Sisodiya, SM, Altmann, A, Ryten, M, Di Nunzio, M, Ravizza, T, Tolomeo, D, Reynolds, RH, Somani, A, Bacigaluppi, M, Iori, V, Micotti, E, Di Sapia, R, Cerovic, M, Palma, E, Ruffolo, G, Botia, JA, Absil, J, Alhusaini, S, Alvim, MKM, Auvinen, P, Bargallo, N, Bartolini, E, Bender, B, Bergo, FPG, Bernardes, T, Bernasconi, A, Bernasconi, N, Bernhardt, BC, Blackmon, K, Braga, B, Caligiuri, ME, Calvo, A, Carlson, C, Carr, SJA, Cavalleri, GL, Cendes, F, Chen, J, Chen, S, Cherubini, A, Concha, L, David, P, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP, Domin, M, Focke, NK, Foley, S, Franca, W, Gambardella, A, Guerrini, R, Hamandi, K, Hibar, DP, Isaev, D, Jackson, GD, Jahanshad, N, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kowalczyk, MA, Kuzniecky, R, Kwan, P, Labate, A, Langner, S, Lenge, M, Liu, M, Martin, P, Mascalchi, M, Meletti, S, Morita-Sherman, ME, O'Brien, TJ, Pariente, JC, Richardson, MP, Rodriguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, MK, Severino, M, Striano, P, Thesen, T, Thomas, RH, Tondelli, M, Tortora, D, Vaudano, AE, Vivash, L, Podewils, F, Wagner, J, Weber, B, Wiest, R, Yasuda, CL, Zhang, G, Zhang, J, Leu, C, Avbersek, A, Thom, M, Whelan, CD, Thompson, P, McDonald, CR, Vezzani, A, and Sisodiya, SM
Abstract: AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.
Published: 2022

6. Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

Author: Lariviere, S, Royer, J, Rodriguez-Cruces, R, Paquola, C, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, CL, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Lui, E, Vaudano, AE, Meletti, S, Tondelli, M, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Winston, GP, Griffin, A, Singh, A, Tiwari, VK, Kreilkamp, BAK, Lenge, M, Guerrini, R, Hamandi, K, Foley, S, Ruber, T, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Kaestner, E, Hatton, SN, Vos, SB, Caciagli, L, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, Bernhardt, BC, Lariviere, S, Royer, J, Rodriguez-Cruces, R, Paquola, C, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, CL, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Lui, E, Vaudano, AE, Meletti, S, Tondelli, M, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Winston, GP, Griffin, A, Singh, A, Tiwari, VK, Kreilkamp, BAK, Lenge, M, Guerrini, R, Hamandi, K, Foley, S, Ruber, T, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Kaestner, E, Hatton, SN, Vos, SB, Caciagli, L, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, and Bernhardt, BC
Abstract: Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.
Published: 2022

7. Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study

Author: Gleichgerrcht, E, Munsell, BC, Alhusaini, S, Alvim, MKM, Bargallo, N, Bender, B, Bernasconi, A, Bernasconi, N, Bernhardt, B, Blackmon, K, Caligiuri, ME, Cendes, F, Concha, L, Desmond, PM, Devinsky, O, Doherty, CP, Domin, M, Duncan, JS, Focke, NK, Gambardella, A, Gong, B, Guerrini, R, Hatton, SN, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kreilkamp, BAK, Labate, A, Langner, S, Lariviere, S, Lenge, M, Lui, E, Martin, P, Mascalchi, M, Meletti, S, O'Brien, TJ, Pardoe, HR, Pariente, JC, Rao, JX, Richardson, MP, Rodriguez-Cruces, R, Ruber, T, Sinclair, B, Soltanian-Zadeh, H, Stein, DJ, Striano, P, Taylor, PN, Thomas, RH, Vaudano, AE, Vivash, L, von Podewills, F, Vos, SB, Weber, B, Yao, Y, Yasuda, CL, Zhang, J, Thompson, PM, Sisodiya, SM, McDonald, CR, Bonilha, L, Gleichgerrcht, E, Munsell, BC, Alhusaini, S, Alvim, MKM, Bargallo, N, Bender, B, Bernasconi, A, Bernasconi, N, Bernhardt, B, Blackmon, K, Caligiuri, ME, Cendes, F, Concha, L, Desmond, PM, Devinsky, O, Doherty, CP, Domin, M, Duncan, JS, Focke, NK, Gambardella, A, Gong, B, Guerrini, R, Hatton, SN, Kalviainen, R, Keller, SS, Kochunov, P, Kotikalapudi, R, Kreilkamp, BAK, Labate, A, Langner, S, Lariviere, S, Lenge, M, Lui, E, Martin, P, Mascalchi, M, Meletti, S, O'Brien, TJ, Pardoe, HR, Pariente, JC, Rao, JX, Richardson, MP, Rodriguez-Cruces, R, Ruber, T, Sinclair, B, Soltanian-Zadeh, H, Stein, DJ, Striano, P, Taylor, PN, Thomas, RH, Vaudano, AE, Vivash, L, von Podewills, F, Vos, SB, Weber, B, Yao, Y, Yasuda, CL, Zhang, J, Thompson, PM, Sisodiya, SM, McDonald, CR, and Bonilha, L
Abstract: Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.
Published: 2021

8. DTI-BASED EVIDENCE FOR IMPAIRED INTEGRITY OF MAJOR WHITE MATTER TRACTS IN NON-LESIONAL TEMPORAL LOBE EPILEPSY: p446

Author: Whelan, C., Alhusaini, S., Meany, J. F. M., Boyle, G., Fagan, A., Fitzsimons, M., OʼHanlon, E., Doherty, C., Delanty, N., and Cavalleri, G. L.
Published: 2012

9. Genetic architecture of subcortical brain structures in 38,854 individuals worldwide

Author: Satizabal, C., Adams, H., Hibar, D., White, C., Knol, M., Stein, J., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G., Smith, A., Bis, J., Jian, X., Luciano, M., Hofer, E., Teumer, A., Van der Lee, S., Yang, J., Yanek, L., Lee, T., Li, S., Hu, Y., Koh, J., Eicher, J., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M., Kim, S., Höhn, D., Armstrong, N., Chen, Q., Holmes, A., Den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A., Jones, H., Pike, G., Stein, D., Stevens, A., Bralten, J., Vernooij, M., Harris, T., Filippi, I., Witte, A., Guadalupe, T., Wittfeld, K., Mosley, T., Becker, J., Doan, N., Hagenaars, S., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Karbalai, N., Arfanakis, K., Becker, D., Ames, D., Goldman, A., Lee, P., Boomsma, D., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M., Kasperaviciute, D., Schmaal, L., Lawrie, S., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G., Shin, J., Ipser, J., Vinke, L., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U., Aribisala, B., Schmidt, H., Strike, L., Cheng, C., Risacher, S., Pütz, B., Fleischman, D., Assareh, A., Mattay, V., Buckner, R., Mecocci, P., Dale, A., Cichon, S., Boks, M., Matarin, M., Penninx, B., Calhoun, V., Chakravarty, M., Marquand, A., Macare, C., Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J., Schork, A., Liewald, D., De Zubicaray, G., Wong, T., Shen, L., Sämann, P., Brodaty, H., Roffman, J., De Geus, E., Tsolaki, M., Erk, S., Van Eijk, K., Cavalleri, G., Van der Wee, N., McIntosh, A., Gollub, R., Bulayeva, K., Bernard, M., Richards, J., Himali, J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L., Valdés Hernández, M., Hansell, N., Van Erp, T., Wolf, C., Kwok, J., Vellas, B., Heinz, A., Olde Loohuis, L., Delanty, N., Ho, B., Ching, C., Shumskaya, E., Singh, B., Hofman, A., Van der Meer, D., Homuth, G., Psaty, B., Bastin, M., Montgomery, G., Foroud, T., Reppermund, S., Hottenga, J., Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C., Van Donkelaar, M., Yang, Q., Hosten, N., Green, R., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H., Lin, H., Jack Jr., C., Schofield, P., Mühleisen, T., Maillard, P., Potkin, S., Wen, W., Fletcher, E., Toga, A., Gruber, O., Huentelman, M., Smith, G., Launer, L., Nyberg, L., Jönsson, E., Crespo-Facorro, B., Koen, N., Greve, D., Uitterlinden, A., Weinberger, D., Steen, V., Fedko, I., Groenewold, N., Niessen, W., Toro, R., Tzourio, C., Longstreth Jr., W., Ikram, M., Smoller, J., Van Tol, M., Sussmann, J., Paus, T., Lemaître, H., Schroeter, M., Mazoyer, B., Andreassen, O., Holsboer, F., Depondt, C., Veltman, D., Turner, J., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I., McMahon, K., Müller-Myhsok, B., Brouwer, R., Soininen, H., Pandolfo, M., Wassink, T., Cheung, J., Wolfers, T., Martinot, J., Zwiers, M., Nauck, M., Melle, I., Martin, N., Kanai, R., Westman, E., Kahn, R., Sisodiya, S., White, T., Saremi, A., Van Bokhoven, H., Brunner, H., Völzke, H., Wright, M., Van 't Ent, D., Nöthen, M., Ophoff, R., Buitelaar, J., Fernández, G., Sachdev, P., Rietschel, M., Van Haren, N., Fisher, S., Beiser, A., Francks, C., Saykin, A., Mather, K., Romanczuk-Seiferth, N., Hartman, C., DeStefano, A., Heslenfeld, D., Weiner, M., Walter, H., Hoekstra, P., Nyquist, P., Franke, B., Bennett, D., Grabe, H., Johnson, A., Chen, C., Van Duijn, C., Lopez, O., Fornage, M., Wardlaw, J., Schmidt, R., DeCarli, C., De Jager, P., Villringer, A., Debette, S., Gudnason, V., Medland, S., Shulman, J., Thompson, P., and Seshadri, S.
Subjects: nervous system
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019

10. 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., McMahon, M.A., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A. de, Alnaes, 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., Bulow, R., Burger, C., Cannon, D.M., Chakravarty, M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., Araujo, T.K. de, Zubicaray, G.I. de, Zwarte, S.M.C. de, 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, Mark F., 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., Kramer, 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., Franke, B., 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., McMahon, M.A., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A. de, Alnaes, 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., Bulow, R., Burger, C., Cannon, D.M., Chakravarty, M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., Araujo, T.K. de, Zubicaray, G.I. de, Zwarte, S.M.C. de, 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, Mark F., 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., Kramer, 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., Franke, B., Thompson, P.M., and Medland, S.E.
Abstract: Contains fulltext : 218611.pdf (Publisher’s version ) (Closed access), The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

11. The genetic architecture of the human cerebral cortex

Author: Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnæs, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bülow, R, Bürger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Doan, NT, Dohm, K, Ehrlich, S, Engelbrecht, HR, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ ; https://orcid.org/0000-0002-9361-4874, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, JJ, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Krämer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Quide, Yann ; https://orcid.org/0000-0002-8569-7139, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Carr, Vaughan ; https://orcid.org/0000-0002-8907-5804, Thalamuthu, Anbu ; https://orcid.org/0000-0002-7114-1260, Brodaty, Henry ; https://orcid.org/0000-0001-9487-6617, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Wen, Wei ; https://orcid.org/0000-0003-2753-3870, Trollor, Julian ; https://orcid.org/0000-0002-7685-2977, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, Mather, Karen ; https://orcid.org/0000-0003-4143-8941, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnæs, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bülow, R, Bürger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Doan, NT, Dohm, K, Ehrlich, S, Engelbrecht, HR, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ ; https://orcid.org/0000-0002-9361-4874, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, JJ, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Krämer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Quide, Yann ; https://orcid.org/0000-0002-8569-7139, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Carr, Vaughan ; https://orcid.org/0000-0002-8907-5804, Thalamuthu, Anbu ; https://orcid.org/0000-0002-7114-1260, Brodaty, Henry ; https://orcid.org/0000-0001-9487-6617, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Wen, Wei ; https://orcid.org/0000-0003-2753-3870, Trollor, Julian ; https://orcid.org/0000-0002-7685-2977, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, and Mather, Karen ; https://orcid.org/0000-0003-4143-8941
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

12. Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study

Author: Lariviere, S, Rodriguez-Cruces, R, Royer, J, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, Bernhardt, BC, Lariviere, S, Rodriguez-Cruces, R, Royer, J, Caligiuri, ME, Gambardella, A, Concha, L, Keller, SS, Cendes, F, Yasuda, C, Bonilha, L, Gleichgerrcht, E, Focke, NK, Domin, M, von Podewills, F, Langner, S, Rummel, C, Wiest, R, Martin, P, Kotikalapudi, R, O'Brien, TJ, Sinclair, B, Vivash, L, Desmond, PM, Alhusaini, S, Doherty, CP, Cavalleri, GL, Delanty, N, Kalviainen, R, Jackson, GD, Kowalczyk, M, Mascalchi, M, Semmelroch, M, Thomas, RH, Soltanian-Zadeh, H, Davoodi-Bojd, E, Zhang, J, Lenge, M, Guerrini, R, Bartolini, E, Hamandi, K, Foley, S, Weber, B, Depondt, C, Absil, J, Carr, SJA, Abela, E, Richardson, MP, Devinsky, O, Severino, M, Striano, P, Tortora, D, Hatton, SN, Vos, SB, Duncan, JS, Whelan, CD, Thompson, PM, Sisodiya, SM, Bernasconi, A, Labate, A, McDonald, CR, Bernasconi, N, and Bernhardt, BC
Abstract: Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.
Published: 2020

13. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: SATIZABAL, C. L., ADAMS, H. H. H., HIBAR, D. P., WHITE, C. C., KNOL, M. J., STEIN, J. L., Scholz, M., Sargurupremraj, Muralidharan, JAHANSHAD, N., ROSHCHUPKIN, G. V., SMITH, A. V., BIS, J. C., JIAN, X., LUCIANO, M., Hofer, E., TEUMER, A., VAN DER LEE, S. J., Yang, J., YANEK, L. R., LEE, T. V., Li, S., Hu, Y., KOH, J. Y., EICHER, J. D., DESRIVIERES, S., ARIAS-VASQUEZ, A., Chauhan, G., ATHANASIU, L., RENTERIA, M. E., Kim, S., HOEHN, D., ARMSTRONG, N. J., Chen, Q., HOLMES, A. J., DEN BRABER, A., KLOSZEWSKA, I., Andersson, M., ESPESETH, T., Grimm, O., ABRAMOVIC, L., ALHUSAINI, S., MILANESCHI, Y., PAPMEYER, M., AXELSSON, T., Ehrlich, S., ROIZ-SANTIANEZ, R., KRAEMER, B., HABERG, A. K., JONES, H. J., Pike, G. B., STEIN, D. J., Stevens, A., BRALTEN, J., VERNOOIJ, M. W., HARRIS, T. B., FILIPPI, I., WITTE, A. V., Guadalupe, T., WITTFELD, K., MOSLEY, T. H., BECKER, J. T., DOAN, N. T., HAGENAARS, S. P., SABA, Y., CUELLAR-PARTIDA, G., Amin, N., HILAL, S., NHO, K., MIRZA-SCHREIBER, N., ARFANAKIS, K., BECKER, D. M., Ames, D., GOLDMAN, A. L., LEE, P. H., Boomsma, D. I., LOVESTONE, S., GIDDALURU, S., LE HELLARD, S., Mattheisen, M., BOHLKEN, M. M., KASPERAVICIUTE, D., SCHMAAL, L., LAWRIE, S. M., Agartz, I., Walton, E., TORDESILLAS-GUTIERREZ, D., DAVIES, G. E., Shin, J., IPSER, J. C., VINKE, L. N., HOOGMAN, M., Jia, T., BURKHARDT, R., Klein, M., Crivello, Fabrice, JANOWITZ, D., CARMICHAEL, O., HAUKVIK, U. K., ARIBISALA, B. S., Schmidt, H., STRIKE, L. T., CHENG, C. Y., RISACHER, S. L., PUTZ, B., FLEISCHMAN, D. A., ASSAREH, A. A., MATTAY, V. S., BUCKNER, R. L., MECOCCI, P., DALE, A. M., Cichon, S., BOKS, M. P., MATARIN, M., PENNINX, Bwjh, CALHOUN, V. D., CHAKRAVARTY, M. M., MARQUAND, A. F., MACARE, C., KHARABIAN MASOULEH, S., OOSTERLAAN, J., Amouyel, P., HEGENSCHEID, K., ROTTER, J. I., SCHORK, A. J., LIEWALD, D. C. M., DE ZUBICARAY, G. I., WONG, T. Y., Shen, L., SAMANN, P. G., BRODATY, H., ROFFMAN, J. L., DE GEUS, E. J. C., TSOLAKI, M., ERK, S., VAN EIJK, K. R., CAVALLERI, G. L., VAN DER WEE, N. J. A., MCINTOSH, A. M., GOLLUB, R. L., BULAYEVA, K. B., Bernard, M., RICHARDS, J. S., HIMALI, J. J., Loeffler, M., ROMMELSE, N., Hoffmann, W., WESTLYE, L. T., VALDES HERNANDEZ, M. C., HANSELL, N. K., VAN ERP, T. G. M., Wolf, C., KWOK, J. B. J., Vellas, B., Heinz, A., OLDE LOOHUIS, L. M., DELANTY, N., HO, B. C., CHING, C. R. K., SHUMSKAYA, E., Singh, B., Hofman, A., VAN DER MEER, D., Homuth, G., PSATY, B. M., BASTIN, M. E., MONTGOMERY, G. W., FOROUD, T. M., REPPERMUND, S., HOTTENGA, J. J., Simmons, A., Meyer-Lindenberg, A., Cahn, W., WHELAN, C. D., VAN DONKELAAR, M. M. J., Yang, Q., HOSTEN, N., GREEN, R. C., THALAMUTHU, A., MOHNKE, S., HULSHOFF POL, H. E., Lin, H., JACK, C. R., Jr., SCHOFIELD, P. R., MUHLEISEN, T. W., MAILLARD, P., POTKIN, S. G., Wen, W., FLETCHER, E., TOGA, A. W., Gruber, O., HUENTELMAN, M., DAVEY SMITH, G., LAUNER, L. J., Nyberg, L., JONSSON, E. G., CRESPO-FACORRO, B., KOEN, N., GREVE, D. N., UITTERLINDEN, A. G., WEINBERGER, D. R., STEEN, V. M., FEDKO, I. O., GROENEWOLD, N. A., Niessen, W. J., TORO, R., Tzourio, Christophe, LONGSTRETH, W. T., Jr., SMOLLER, J. W., VAN TOL, M. J., SUSSMANN, J. E., PAUS, T., Lemaitre, H., SCHROETER, M. L., Mazoyer, B., ANDREASSEN, O. A., Holsboer, F., DEPONDT, C., VELTMAN, D. J., Turner, J. A., PAUSOVA, Z., Schumann, G., Van Rooij, D., Djurovic, S., DEARY, I. J., MCMAHON, K. L., MULLER-MYHSOK, B., BROUWER, R. M., Soininen, H., Pandolfo, M., WASSINK, T. H., CHEUNG, J. W., WOLFERS, T., MARTINOT, J. L., ZWIERS, M. P., Nauck, M., Melle, I., Martin, N. G., Kanai, R., WESTMAN, E., KAHN, R. S., Sisodiya, S. M., White, T., SAREMI, A., van Bokhoven, H., Brunner, H. G., VOLZKE, H., WRIGHT, M. J., VAN 'T ENT, D., NOTHEN, M. M., OPHOFF, R. A., BUITELAAR, J. K., Fernandez, G., SACHDEV, P. S., Rietschel, M., VAN HAREN, N. E. M., Fisher, S. E., BEISER, A. S., Francks, C., SAYKIN, A. J., MATHER, K. A., ROMANCZUK-SEIFERTH, N., HARTMAN, C. A., DeStefano, A. L., HESLENFELD, D. J., WEINER, M. W., Walter, H., HOEKSTRA, P. J., NYQUIST, P. A., Franke, B., BENNETT, D. A., Grabe, H. J., JOHNSON, A. D., Chen, C., VAN DUIJN, C. M., LOPEZ, O. L., FORNAGE, M., WARDLAW, J. M., Schmidt, R., DeCarli, C., DE JAGER, P. L., VILLRINGER, A., Debette, Stephanie, GUDNASON, V., Medland, S. E., SHULMAN, J. M., THOMPSON, P. M., SESHADRI, S., IKRAM, M. K., Bordeaux population health (BPH), 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), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: nervous system, VINTAGE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HEALTHY
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019
Full Text: View/download PDF

14. Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA consortium

Author: Kong, XZ, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Canive, JM, Cannon, DM, Caparelli, EC, Castellanos, FX, Cavalleri, GL, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dale, A, Dannlowski, U, De Bruttopilo, SA, De Zeeuw, P, Deary, IJ, Delanty, N, Demeter, DV, Di Martino, A, and Dickie, EW
Abstract: © 2018 National Academy of Sciences. All rights reserved. Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.
Published: 2018
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15. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: Satizabal, C.L., Adams, H.H.H., Hibar, D.P., White, C.C., Knol, M.J., Stein, J.L., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G.V., Smith, A.V., Bis, J.C., Jian, X., Luciano, M., Hofer, E., Teumer, A., van der Lee, S.J., Yang, J., Yanek, L.R., Lee, T.V., Li, S., Hu, Y., Koh, J.Y., Eicher, J.D., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M.E., Kim, S., Hoehn, D., Armstrong, N.J., Chen, Q., Holmes, A.J., den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A.K., Jones, H.J., Pike, G.B., Stein, D.J., Stevens, A., Bralten, J., Vernooij, M.W., Harris, T.B., Filippi, I., Witte, A.V., Guadalupe, T., Wittfeld, K., Mosley, T.H., Becker, J.T., Doan, N.T., Hagenaars, S.P., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Mirza-Schreiber, N., Arfanakis, K., Becker, D.M., Ames, D., Goldman, A.L., Lee, P.H., Boomsma, D.I., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M.M., Kasperaviciute, D., Schmaal, L., Lawrie, S.M., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G.E., Shin, J., Ipser, J.C., Vinke, L.N., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U.K., Aribisala, B.S., Schmidt, H., Strike, L.T., Cheng, C-Y, Risacher, S.L., Pütz, B., Fleischman, D.A., Assareh, A.A., Mattay, V.S., Buckner, R.L., Mecocci, P., Dale, A.M., Cichon, S., Boks, M.P., Matarin, M., Penninx, B.W.J.H., Calhoun, V.D., Chakravarty, M.M., Marquand, A.F., Macare, C., Kharabian Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J.I., Schork, A.J., Liewald, D.C.M., de Zubicaray, G.I., Wong, T.Y., Shen, L., Sämann, P.G., Brodaty, H., Roffman, J.L., de Geus, E.J.C., Tsolaki, M., Erk, S., van Eijk, K.R., Cavalleri, G.L., van der Wee, N.J.A., McIntosh, A.M., Gollub, R.L., Bulayeva, K.B., Bernard, M., Richards, J.S., Himali, J.J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L.T., Valdés Hernández, M.C., Hansell, N.K., Van Erp, T.G.M., Wolf, C., Kwok, J.B.J., Vellas, B., Heinz, A., Olde Loohuis, L.M., Delanty, N., Ho, B-C., Ching, C.R.K., Shumskaya, E., Singh, B., Hofman, A., van der Meer, D., Homuth, G., Psaty, B.M., Bastin, M.E., Montgomery, G.W., Foroud, T.M., Reppermund, S., Hottenga, J-J, Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C.D., van Donkelaar, M.M.J., Yang, Q., Hosten, N., Green, R.C., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H.E., Lin, H., Jack, C.R., Schofield, P.R., Mühleisen, T.W., Maillard, P., Potkin, S.G., Wen, W., Fletcher, E., Toga, A.W., Gruber, O., Huentelman, M., Davey Smith, G., Launer, L.J., Nyberg, L., Jönsson, E.G., Crespo-Facorro, B., Koen, N., Greve, D.N., Uitterlinden, A.G., Weinberger, D.R., Steen, V.M., Fedko, I.O., Groenewold, N.A., Niessen, W.J., Toro, R., Tzourio, C., Longstreth, W.T., Ikram, M.K., Smoller, J.W., van Tol, M-J, Sussmann, J.E., Paus, T., Lemaitre, H., Schroeter, M.L., Mazoyer, B., Andreassen, O.A., Holsboer, F., Depondt, C., Veltman, D.J., Turner, J.A., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I.J., McMahon, K.L., Müller-Myhsok, B., Brouwer, R.M., Soininen, H., Pandolfo, M., Wassink, T.H., Cheung, J.W., Wolfers, T., Martinot, J-L, Zwiers, M.P., Nauck, M., Melle, I., Martin, N.G., Kanai, R., Westman, E., Kahn, R.S., Sisodiya, S.M., White, T., Saremi, A., van Bokhoven, H., Brunner, H.G., Völzke, H., Wright, M.J., van ‘t Ent, D., Nöthen, M.M., Ophoff, R.A., Buitelaar, J.K., Fernández, G., Sachdev, P.S., Rietschel, M., van Haren, N.E.M., Fisher, S.E., Beiser, A.S., Francks, C., Saykin, A.J., Mather, K.A., Romanczuk-Seiferth, N., Hartman, C.A., DeStefano, A.L., Heslenfeld, D.J., Weiner, M.W., Walter, H., Hoekstra, P.J., Nyquist, P.A., Franke, B., Bennett, D.A., Grabe, H.J., Johnson, A.D., Chen, C., van Duijn, C.M., Lopez, O.L., Fornage, M., Wardlaw, J.M., Schmidt, R., DeCarli, C., De Jager, P.L., Villringer, A., Debette, S., Gudnason, V., Medland, S.E., Shulman, J.M., Thompson, P.M., Seshadri, S., Ikram, M.A., Satizabal, C.L., Adams, H.H.H., Hibar, D.P., White, C.C., Knol, M.J., Stein, J.L., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G.V., Smith, A.V., Bis, J.C., Jian, X., Luciano, M., Hofer, E., Teumer, A., van der Lee, S.J., Yang, J., Yanek, L.R., Lee, T.V., Li, S., Hu, Y., Koh, J.Y., Eicher, J.D., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M.E., Kim, S., Hoehn, D., Armstrong, N.J., Chen, Q., Holmes, A.J., den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A.K., Jones, H.J., Pike, G.B., Stein, D.J., Stevens, A., Bralten, J., Vernooij, M.W., Harris, T.B., Filippi, I., Witte, A.V., Guadalupe, T., Wittfeld, K., Mosley, T.H., Becker, J.T., Doan, N.T., Hagenaars, S.P., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Mirza-Schreiber, N., Arfanakis, K., Becker, D.M., Ames, D., Goldman, A.L., Lee, P.H., Boomsma, D.I., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M.M., Kasperaviciute, D., Schmaal, L., Lawrie, S.M., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G.E., Shin, J., Ipser, J.C., Vinke, L.N., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U.K., Aribisala, B.S., Schmidt, H., Strike, L.T., Cheng, C-Y, Risacher, S.L., Pütz, B., Fleischman, D.A., Assareh, A.A., Mattay, V.S., Buckner, R.L., Mecocci, P., Dale, A.M., Cichon, S., Boks, M.P., Matarin, M., Penninx, B.W.J.H., Calhoun, V.D., Chakravarty, M.M., Marquand, A.F., Macare, C., Kharabian Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J.I., Schork, A.J., Liewald, D.C.M., de Zubicaray, G.I., Wong, T.Y., Shen, L., Sämann, P.G., Brodaty, H., Roffman, J.L., de Geus, E.J.C., Tsolaki, M., Erk, S., van Eijk, K.R., Cavalleri, G.L., van der Wee, N.J.A., McIntosh, A.M., Gollub, R.L., Bulayeva, K.B., Bernard, M., Richards, J.S., Himali, J.J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L.T., Valdés Hernández, M.C., Hansell, N.K., Van Erp, T.G.M., Wolf, C., Kwok, J.B.J., Vellas, B., Heinz, A., Olde Loohuis, L.M., Delanty, N., Ho, B-C., Ching, C.R.K., Shumskaya, E., Singh, B., Hofman, A., van der Meer, D., Homuth, G., Psaty, B.M., Bastin, M.E., Montgomery, G.W., Foroud, T.M., Reppermund, S., Hottenga, J-J, Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C.D., van Donkelaar, M.M.J., Yang, Q., Hosten, N., Green, R.C., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H.E., Lin, H., Jack, C.R., Schofield, P.R., Mühleisen, T.W., Maillard, P., Potkin, S.G., Wen, W., Fletcher, E., Toga, A.W., Gruber, O., Huentelman, M., Davey Smith, G., Launer, L.J., Nyberg, L., Jönsson, E.G., Crespo-Facorro, B., Koen, N., Greve, D.N., Uitterlinden, A.G., Weinberger, D.R., Steen, V.M., Fedko, I.O., Groenewold, N.A., Niessen, W.J., Toro, R., Tzourio, C., Longstreth, W.T., Ikram, M.K., Smoller, J.W., van Tol, M-J, Sussmann, J.E., Paus, T., Lemaitre, H., Schroeter, M.L., Mazoyer, B., Andreassen, O.A., Holsboer, F., Depondt, C., Veltman, D.J., Turner, J.A., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I.J., McMahon, K.L., Müller-Myhsok, B., Brouwer, R.M., Soininen, H., Pandolfo, M., Wassink, T.H., Cheung, J.W., Wolfers, T., Martinot, J-L, Zwiers, M.P., Nauck, M., Melle, I., Martin, N.G., Kanai, R., Westman, E., Kahn, R.S., Sisodiya, S.M., White, T., Saremi, A., van Bokhoven, H., Brunner, H.G., Völzke, H., Wright, M.J., van ‘t Ent, D., Nöthen, M.M., Ophoff, R.A., Buitelaar, J.K., Fernández, G., Sachdev, P.S., Rietschel, M., van Haren, N.E.M., Fisher, S.E., Beiser, A.S., Francks, C., Saykin, A.J., Mather, K.A., Romanczuk-Seiferth, N., Hartman, C.A., DeStefano, A.L., Heslenfeld, D.J., Weiner, M.W., Walter, H., Hoekstra, P.J., Nyquist, P.A., Franke, B., Bennett, D.A., Grabe, H.J., Johnson, A.D., Chen, C., van Duijn, C.M., Lopez, O.L., Fornage, M., Wardlaw, J.M., Schmidt, R., DeCarli, C., De Jager, P.L., Villringer, A., Debette, S., Gudnason, V., Medland, S.E., Shulman, J.M., Thompson, P.M., Seshadri, S., and Ikram, M.A.
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Published: 2019

16. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Author: Whelan, Cd, Altmann, A, Botía, Ja, Jahanshad, N, Hibar, Dp, Absil, J, Alhusaini, S, Alvim, Mkm, Auvinen, P, Bartolini, E, Bergo, Fpg, Bernardes, T, Blackmon, K, Braga, B, Caligiuri, Me, Calvo, A, Carr, Sj, Chen, J, Chen, S, Cherubini, A, David, P, Domin, M, Foley, S, França, W, Haaker, G, Isaev, D, Keller, Ss, Kotikalapudi, R, Kowalczyk, Ma, Kuzniecky, R, Langner, S, Lenge, M, Leyden, Km, Liu, M, Loi, Rq, Martin, P, Mascalchi, M, Morita, Me, Pariente, Jc, Rodríguez-Cruces, R, Rummel, C, Saavalainen, T, Semmelroch, Mk, Severino, M, Thomas, Rh, Tondelli, M, Tortora, D, Vaudano, AE39, Vivash, L40, von Podewils F42, Wagner, J43, Weber, B43, Yao, Y46, Yasuda, CL7, Zhang, G47, Bargalló, N15, Bender, B26, Bernasconi, N, Bernasconi, A, Bernhardt, Bc, Blümcke, I, Carlson, C, Cavalleri, Gl, Cendes, F, Concha, L, Delanty, N, Depondt, C, Devinsky, O, Doherty, CP51, Focke, Nk, Gambardella, A, Guerrini, R, Hamandi, K, Jackson, Gd, Kälviäinen, R, Kochunov, P, Kwan, P, Labate, A, McDonald, Cr, Meletti, S, O'Brien, Tj, Ourselin, S, Richardson MP Striano, P, Thesen, T, Wiest, R, Zhang, J, Vezzani, A, Ryten, M, Thompson, Pm, and Sisodiya, Sm.
Subjects: MRI, epilepsy, precentral gyrus, thalamus
Published: 2018

17. P.097 Subarachnoid hemorrhage associated with a thromboembolic ischemic stroke- an unexpected observation

Author: Almutlaq, A, primary, Alhusaini, S, additional, Chalk, C, additional, and Cote, R, additional
Published: 2018
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18. GP.01 The relationship between carotid stenosis, cerebral cortex thickness and cognitive function in community dwelling older individuals

Author: Alhusaini, S, primary, Karama, S, additional, Star, JM, additional, Bastin, ME, additional, Wardlaw, JM, additional, Deary, IJ, additional, and Ducharme, S, additional
Published: 2018
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19. Novel genetic loci associated with hippocampal volume

Author: Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivières, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Doan, NT, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jørgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, and Lee, PH
Abstract: © The Author(s) 2017. The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
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20. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author: Adams, HHH, Hibar, DP, Chouraki, V, Stein, JL, Nyquist, PA, Rentería, ME, Trompet, S, Arias-Vasquez, A, Seshadri, S, Desrivières, S, Beecham, AH, Jahanshad, N, Wittfeld, K, Van Der Lee, SJ, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beiser, A, Bernard, M, Bis, JC, Blanken, LME, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chauhan, G, Chen, Q, Ching, CRK, Cuellar-Partida, G, Braber, AD, Doan, NT, Ehrlich, S, Filippi, I, Ge, T, Giddaluru, S, Goldman, AL, Gottesman, RF, Greven, CU, Grimm, O, Griswold, ME, Guadalupe, T, Hass, J, Haukvik, UK, Hilal, S, Hofer, E, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, and Jia, T
Abstract: © 2016 Nature America, Inc., part of Springer Nature. All rights reserved. Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
Published: 2016
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21. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author: Thompson, P, Stein, J, Medland, SE, Hibar, D, Vasquez, A, Renteria, M, Toro, R, Jahanshad, N, Schumann, G, Franke, B, Wright, M, Martin, N, Agartz, I, Alda, M, Alhusaini, S, Almasy, L, and Almeida, J
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. © 2014 The Author(s).
Published: 2016

22. Novel genetic loci associated with hippocampal volume

Author: Hibar, D.P. (Derrek), Adams, H.H.H. (Hieab), Jahanshad, N. (Neda), Chauhan, G. (Ganesh), Stein, J.L., Hofer, E. (Edith), Rentería, M.E. (Miguel), Bis, J.C. (Joshua), Arias-Vásquez, A. (Alejandro), Ikram, M.K. (M. Kamran), Desrivières, S. (Sylvane), Vernooij, M.W. (Meike), Abramovic, L. (Lucija), Alhusaini, S. (Saud), Amin, N. (Najaf), Andersson, M. (Micael), Arfanakis, K. (Konstantinos), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Athanasiu, L. (Lavinia), Axelsson, T. (Tomas), Beecham, A.H. (Ashley), Beiser, A. (Alexa), Bernard, M. (Manon), Blanton, S.H. (Susan H.), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brickman, A.M. (Adam M.), Carmichael, O. (Owen), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Chouraki, V. (Vincent), Cuellar-Partida, G. (Gabriel), Crivello, F. (Fabrice), Braber, A. (Anouk) den, Doan, N.T. (Nhat Trung), Ehrlich, S.M. (Stefan), Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Gottesman, R.F. (Rebecca), Grimm, O. (Oliver), Griswold, M.D. (Michael), Guadalupe, T. (Tulio), Gutman, B.A. (Boris A.), Hass, J. (Johanna), Haukvik, U.K. (Unn), Hoehn, D. (David), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Jørgensen, K.N. (Kjetil N.), Karbalai, N. (Nazanin), Kasperaviciute, D. (Dalia), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Luciano, M. (Michelle), MacAre, C. (Christine), Marquand, A.F. (Andre F.), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), McKay, D.R. (David R.), Milaneschi, Y. (Yuri), Muñoz Maniega, S. (Susana), Nho, K. (Kwangsik), Nugent, A.C. (Allison), Nyquist, P. (Paul), Loohuis, L.M.O. (Loes M. Olde), Oosterlaan, J. (Jaap), Papmeyer, M. (Martina), Pirpamer, L. (Lukas), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Richards, J.S. (Jennifer S.), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rommelse, N. (Nanda), Ropele, S. (Stefan), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rundek, T. (Tatjana), Sämann, P.G. (Philipp), Saremi, A. (Arvin), Satizabal, C.L. (Claudia), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shen, L. (Li), Shin, J. (Jean), Shumskaya, E. (Elena), Smith, A.V. (Albert Vernon), Sprooten, R. (Roy), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Tordesillas-Gutierrez, D. (Diana), Toro, R. (Roberto), Trabzuni, D. (Danyah), Trompet, S. (Stella), Vaidya, D. (Dhananjay), van der Grond, J. (Jeroen), Lee, S.J. (Sven) van der, Van Der Meer, D. (Dennis), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Van Rooij, D. (Daan), Walton, E. (Esther), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Windham, B.G. (Gwen), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Wolfers, T. (Thomas), Yanek, L.R. (Lisa), Yang, J. (Jingyun), Zijdenbos, A.P., Zwiers, M.P. (Marcel), Agartz, I. (Ingrid), Almasy, L. (Laura), Ames, D.J. (David), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Arepalli, S. (Sampath), Assareh, A.A., Barral, S. (Sandra), Bastin, M.E. (Mark), Becker, D.M. (Diane M.), Becker, J.T. (James), Bennett, D.A. (David A.), Blangero, J. (John), Bokhoven, H. (Hans) van, Boomsma, D.I. (Dorret), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cavalleri, G. (Gianpiero), Cheng, C.-Y. (Ching-Yu), Cichon, S. (Sven), Cookson, M.R. (Mark), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Dale, A.M. (Anders), Davies, G.E. (Gareth), Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Jager, P.L. (Philip) de, Zubicaray, G.I. (Greig) de, Deary, I.J. (Ian), Debette, S. (Stéphanie), DeCarli, C. (Charles), Delanty, N., Depondt, C. (Chantal), DeStefano, A.L. (Anita), Dillman, A. (Allissa), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drevets, D.A. (Douglas), Duggirala, R. (Ravi), Dyer, M.D. (Matthew), Enzinger, C. (Christian), Erk, S., Espeseth, T. (Thomas), Fedko, I.O. (Iryna O.), Fernández, G. (Guillén), Ferrucci, L. (Luigi), Fisher, S.E. (Simon), Fleischman, D. (Debra), Ford, I. (Ian), Fornage, M. (Myriam), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Fukunaga, M. (Masaki), Gibbs, J.R. (J. Raphael), Glahn, D.C. (David), Gollub, R.L. (Randy), Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Gruber, O. (Oliver), Gudnason, V. (Vilmundur), Guelfi, S. (Sebastian), Håberg, A.K. (Asta K.), Hansell, N.K. (Narelle), Hardy, J. (John), Hartman, C.A. (C.), Hashimoto, R. (Ryota), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Le Hellard, S. (Stephanie), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Holsboer, F. (Florian), Homuth, G. (Georg), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Huentelman, M.J. (Matthew), Pol, H.H., Ikeda, M. (Masashi), Jack, C.R. (Clifford R.), Jenkinson, S. (Sarah), Johnson, R. (Robert), Jönsson, E.G. (Erik G.), Jukema, J.W., Kahn, R. (René), Kanai, R. (Ryota), Kloszewska, I. (Iwona), Knopman, D.S. (David S.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Lemaître, H. (Herve), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Lopez, O.L. (Oscar L.), Lovestone, S. (Simon), Martinez, O. (Oliver), Martinot, J.-L. (Jean-Luc), Mattay, V.S. (Venkata S.), McDonald, C. (Colm), McIntosh, A.M. (Andrew), McMahon, F.J. (Francis J.), McMahon, K.L. (Katie L.), Mecocci, P. (Patrizia), Melle, I. (Ingrid), Meyer-Lindenberg, A. (Andreas), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant W.), Morris, D.W. (Derek W), Mosley, T.H. (Thomas H.), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (B.), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nichols, T.E. (Thomas), Niessen, W.J. (Wiro), Nöthen, M.M. (Markus), Nyberg, L. (Lars), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Paus, T. (Tomas), Pausova, Z. (Zdenka), Penninx, B.W.J.H. (Brenda), Pike, G.B. (G. Bruce), Potkin, S.G. (Steven), Psaty, B.M. (Bruce), Reppermund, S., Rietschel, M. (Marcella), Roffman, J.L. (Joshua), Seiferth, N. (Nina), Rotter, J.I. (Jerome I.), Ryten, M. (Mina), Sacco, R.L. (Ralph L.), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, C.J. (Christopher), Sigursson, S. (Sigurdur), Simmons, A. (Andrew), Singleton, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soininen, H. (H.), Steen, V.M. (Vidar), Stott, D.J. (David J.), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Tsolaki, M. (Magda), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Hernández, M.C.V. (Maria C. Valdés), Brug, M.P. (Marcel) van der, Lugt, A. (Aad) van der, Wee, N.J. (Nic) van der, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Vardarajan, B.N. (Badri), Vellas, B. (Bruno), Veltman, D.J. (Dick), Völzke, H. (Henry), Walter, H.J. (Henrik), Wardlaw, J. (Joanna), Wassink, A.M.J. (Annemarie), Weale, M.E. (Michael), Weinberger, D.R. (Daniel R.), Weiner, M.W. (Michael W.), Wen, W. (Wei), Westman, E. (Eric), White, T.J.H. (Tonya), Wong, T.Y. (Tien Y.), Wright, C.B. (Clinton B.), Zielke, R.H. (Ronald H.), Zonderman, A.B., Martin, N.G. (Nicholas), Duijn, C.M. (Cornelia) van, Wright, M.J. (Margaret), Longstreth Jr, W.T., Schumann, G. (Gunter), Grabe, H.J. (Hans Jörgen), Franke, B. (Barbara), Launer, L.J. (Lenore), Medland, S.E. (Sarah), Seshadri, S. (Sudha), Thompson, P.M. (Paul), Ikram, M.K. (Kamran), Hibar, D.P. (Derrek), Adams, H.H.H. (Hieab), Jahanshad, N. (Neda), Chauhan, G. (Ganesh), Stein, J.L., Hofer, E. (Edith), Rentería, M.E. (Miguel), Bis, J.C. (Joshua), Arias-Vásquez, A. (Alejandro), Ikram, M.K. (M. Kamran), Desrivières, S. (Sylvane), Vernooij, M.W. (Meike), Abramovic, L. (Lucija), Alhusaini, S. (Saud), Amin, N. (Najaf), Andersson, M. (Micael), Arfanakis, K. (Konstantinos), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Athanasiu, L. (Lavinia), Axelsson, T. (Tomas), Beecham, A.H. (Ashley), Beiser, A. (Alexa), Bernard, M. (Manon), Blanton, S.H. (Susan H.), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brickman, A.M. (Adam M.), Carmichael, O. (Owen), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Chouraki, V. (Vincent), Cuellar-Partida, G. (Gabriel), Crivello, F. (Fabrice), Braber, A. (Anouk) den, Doan, N.T. (Nhat Trung), Ehrlich, S.M. (Stefan), Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Gottesman, R.F. (Rebecca), Grimm, O. (Oliver), Griswold, M.D. (Michael), Guadalupe, T. (Tulio), Gutman, B.A. (Boris A.), Hass, J. (Johanna), Haukvik, U.K. (Unn), Hoehn, D. (David), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Jørgensen, K.N. (Kjetil N.), Karbalai, N. (Nazanin), Kasperaviciute, D. (Dalia), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Luciano, M. (Michelle), MacAre, C. (Christine), Marquand, A.F. (Andre F.), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), McKay, D.R. (David R.), Milaneschi, Y. (Yuri), Muñoz Maniega, S. (Susana), Nho, K. (Kwangsik), Nugent, A.C. (Allison), Nyquist, P. (Paul), Loohuis, L.M.O. (Loes M. Olde), Oosterlaan, J. (Jaap), Papmeyer, M. (Martina), Pirpamer, L. (Lukas), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Richards, J.S. (Jennifer S.), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rommelse, N. (Nanda), Ropele, S. (Stefan), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rundek, T. (Tatjana), Sämann, P.G. (Philipp), Saremi, A. (Arvin), Satizabal, C.L. (Claudia), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shen, L. (Li), Shin, J. (Jean), Shumskaya, E. (Elena), Smith, A.V. (Albert Vernon), Sprooten, R. (Roy), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Tordesillas-Gutierrez, D. (Diana), Toro, R. (Roberto), Trabzuni, D. (Danyah), Trompet, S. (Stella), Vaidya, D. (Dhananjay), van der Grond, J. (Jeroen), Lee, S.J. (Sven) van der, Van Der Meer, D. (Dennis), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Van Rooij, D. (Daan), Walton, E. (Esther), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Windham, B.G. (Gwen), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Wolfers, T. (Thomas), Yanek, L.R. (Lisa), Yang, J. (Jingyun), Zijdenbos, A.P., Zwiers, M.P. (Marcel), Agartz, I. (Ingrid), Almasy, L. (Laura), Ames, D.J. (David), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Arepalli, S. (Sampath), Assareh, A.A., Barral, S. (Sandra), Bastin, M.E. (Mark), Becker, D.M. (Diane M.), Becker, J.T. (James), Bennett, D.A. (David A.), Blangero, J. (John), Bokhoven, H. (Hans) van, Boomsma, D.I. (Dorret), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cavalleri, G. (Gianpiero), Cheng, C.-Y. (Ching-Yu), Cichon, S. (Sven), Cookson, M.R. (Mark), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Dale, A.M. (Anders), Davies, G.E. (Gareth), Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Jager, P.L. (Philip) de, Zubicaray, G.I. (Greig) de, Deary, I.J. (Ian), Debette, S. (Stéphanie), DeCarli, C. (Charles), Delanty, N., Depondt, C. (Chantal), DeStefano, A.L. (Anita), Dillman, A. (Allissa), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drevets, D.A. (Douglas), Duggirala, R. (Ravi), Dyer, M.D. (Matthew), Enzinger, C. (Christian), Erk, S., Espeseth, T. (Thomas), Fedko, I.O. (Iryna O.), Fernández, G. (Guillén), Ferrucci, L. (Luigi), Fisher, S.E. (Simon), Fleischman, D. (Debra), Ford, I. (Ian), Fornage, M. (Myriam), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Fukunaga, M. (Masaki), Gibbs, J.R. (J. Raphael), Glahn, D.C. (David), Gollub, R.L. (Randy), Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Gruber, O. (Oliver), Gudnason, V. (Vilmundur), Guelfi, S. (Sebastian), Håberg, A.K. (Asta K.), Hansell, N.K. (Narelle), Hardy, J. (John), Hartman, C.A. (C.), Hashimoto, R. (Ryota), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Le Hellard, S. (Stephanie), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Holsboer, F. (Florian), Homuth, G. (Georg), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Huentelman, M.J. (Matthew), Pol, H.H., Ikeda, M. (Masashi), Jack, C.R. (Clifford R.), Jenkinson, S. (Sarah), Johnson, R. (Robert), Jönsson, E.G. (Erik G.), Jukema, J.W., Kahn, R. (René), Kanai, R. (Ryota), Kloszewska, I. (Iwona), Knopman, D.S. (David S.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Lemaître, H. (Herve), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Lopez, O.L. (Oscar L.), Lovestone, S. (Simon), Martinez, O. (Oliver), Martinot, J.-L. (Jean-Luc), Mattay, V.S. (Venkata S.), McDonald, C. (Colm), McIntosh, A.M. (Andrew), McMahon, F.J. (Francis J.), McMahon, K.L. (Katie L.), Mecocci, P. (Patrizia), Melle, I. (Ingrid), Meyer-Lindenberg, A. (Andreas), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant W.), Morris, D.W. (Derek W), Mosley, T.H. (Thomas H.), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (B.), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nichols, T.E. (Thomas), Niessen, W.J. (Wiro), Nöthen, M.M. (Markus), Nyberg, L. (Lars), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Paus, T. (Tomas), Pausova, Z. (Zdenka), Penninx, B.W.J.H. (Brenda), Pike, G.B. (G. Bruce), Potkin, S.G. (Steven), Psaty, B.M. (Bruce), Reppermund, S., Rietschel, M. (Marcella), Roffman, J.L. (Joshua), Seiferth, N. (Nina), Rotter, J.I. (Jerome I.), Ryten, M. (Mina), Sacco, R.L. (Ralph L.), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, C.J. (Christopher), Sigursson, S. (Sigurdur), Simmons, A. (Andrew), Singleton, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soininen, H. (H.), Steen, V.M. (Vidar), Stott, D.J. (David J.), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Tsolaki, M. (Magda), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Hernández, M.C.V. (Maria C. Valdés), Brug, M.P. (Marcel) van der, Lugt, A. (Aad) van der, Wee, N.J. (Nic) van der, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Vardarajan, B.N. (Badri), Vellas, B. (Bruno), Veltman, D.J. (Dick), Völzke, H. (Henry), Walter, H.J. (Henrik), Wardlaw, J. (Joanna), Wassink, A.M.J. (Annemarie), Weale, M.E. (Michael), Weinberger, D.R. (Daniel R.), Weiner, M.W. (Michael W.), Wen, W. (Wei), Westman, E. (Eric), White, T.J.H. (Tonya), Wong, T.Y. (Tien Y.), Wright, C.B. (Clinton B.), Zielke, R.H. (Ronald H.), Zonderman, A.B., Martin, N.G. (Nicholas), Duijn, C.M. (Cornelia) van, Wright, M.J. (Margaret), Longstreth Jr, W.T., Schumann, G. (Gunter), Grabe, H.J. (Hans Jörgen), Franke, B. (Barbara), Launer, L.J. (Lenore), Medland, S.E. (Sarah), Seshadri, S. (Sudha), Thompson, P.M. (Paul), and Ikram, M.K. (Kamran)
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
Full Text: View/download PDF

23. Novel genetic loci associated with hippocampal volume

Author: Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., Ikram, M.A., Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., and Ikram, M.A.
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017

24. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author: Thompson, P.M., Stein, J.L., Medland, S.E., Hibar, D.P., Arias Vasquez, A., Renteria, M.E., Toro, R., Jahanshad, N., Schumann, G., Franke, B., Wright, M.J., Martin, N.G., Agartz, I., Alda, M., Alhusaini, S., Almasy, L., Almeida, J., Alpert, K., Andreasen, N.C., Andreassen, O.A., Apostolova, L.G., Appel, K., Armstrong, N.J., Aribisala, B., Bastin, M.E., Bauer, M., Bearden, C.E., Bergmann, O., Binder, E.B., Blangero, J., Bockholt, H.J., Boen, E., Bois, C., Boomsma, D.I., Booth, T., Bowman, I.J., Bralten, J., Brouwer, R.M., Brunner, H.G., Brohawn, D.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K., Bustillo, J.R., Calhoun, V.D., Cannon, D.M., Cantor, R.M., Carless, M.A., Caseras, X., Cavalleri, G.L., Chakravarty, M.M., Chang, K.D., Ching, C.R., Christoforou, A., Cichon, S., Clark, V.P., Conrod, P., Coppola, G., Crespo-Facorro, B., Curran, J.E., Czisch, M., Deary, I.J., Geus, E.J. de, Braber, A., Delvecchio, G., Depondt, C., Haan, L. de, Zubicaray, G.I. de, Dima, D., Dimitrova, R., Djurovic, S., Dong, H., Donohoe, G., Duggirala, R., Dyer, T.D., Ehrlich, S., Ekman, C.J., Elvsashagen, T., Emsell, L., Erk, S., Espeseth, T., Fagerness, J., Fears, S., Fedko, I., Fernandez, G.S.E., Fisher, S.E., Foroud, T., Fox, P.T., Francks, C., Frangou, S., Frey, E.M., Frodl, T., Frouin, V., Garavan, H., Giddaluru, S., Glahn, D.C., Godlewska, B., Goldstein, R.Z., Gollub, R.L., and Grabe, H.J.
Subjects: Neuroinformatics, endocrine system, Multi-site, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Neuroimaging, Medical and Health Sciences, Meta-Analysis as Topic, Clinical Research, 130 000 Cognitive Neurology & Memory, Saguenay Youth Study (SYS) Group, Genetics, Humans, 2.1 Biological and endogenous factors, GWAS, Cooperative Behavior, Aetiology, IMAGEN Consortium, Brain Mapping, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], EPIGEN Consortium, 120 000 Neuronal Coherence, Psychology and Cognitive Sciences, Neurosciences, Experimental Psychology, Alzheimer’s Disease Neuroimaging Initiative, Brain Disorders, Meta-analysis, Mental Health, Good Health and Well Being, Neurological, Schizophrenia, Biomedical Imaging, Consortium, Genome-Wide Association Study, MRI
Abstract: Contains fulltext : 127593.pdf (Publisher’s version ) (Open Access) The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. 30 p.
Published: 2014

25. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author: Adams, H.H.H., Hibar, D.P., Chouraki, V., Stein, J.L., Nyquist, P.A., Renteria, M.E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A.H., Jahanshad, N., Wittfeld, K., van der Lee, S.J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beiser, A., Bernard, M., Bis, J.C., Blanken, L.M.E., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chauhan, G., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., Braber, A.D., Doan, N.T., Ehrlich, S., Filippi, I., Ge, T., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Greven, C.U., Grimm, O., Griswold, M.E., Guadalupe, T., Hass, J., Haukvik, U.K., Hilal, S., Hofer, E., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liao, J., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A., Matarin, M., Mather, K.A., Mattheisen, M., Mazoyer, B., McKay, D.R., McWhirter, R., Milaneschi, Y., Mirza-Schreiber, N., Muetzel, R.L., Maniega, S.M., Nho, K., Nugent, A.C., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pappa, I., Pirpamer, L., Pudas, S., Pütz, B., Rajan, K.B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Thomson, R., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Vaidya, D., Van der Grond, J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Woldehawariat, G., Wolf, C., Wolfers, T., Xu, B., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Aggarwal, N.T., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Chen, C., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., De Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Erk, S., Espeseth, T., Evans, D.A., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Grabe, H.J., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Pol, H.E.H., Ikeda, M., Ikram, M.K., Jack, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Longstreth, W.T., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, K.L., McMahon, F.J., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schofield, P.R., Sigurdsson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Srikanth, V., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Tiemeier, H., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., Van der Lugt, A., van der Wee, N.J.A., van Duijn, C.M., van Haren, N.E.M., Van′t Ent, D., van Tol, M-J, Vardarajan, B.N., Veltman, D.J., Vernooij, M.W., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, H.R., Zonderman, A.B., Deary, I.J., DeCarli, C., Schmidt, H., Martin, N.G., de Craen, A.J.M., Wright, M.J., Launer, L.J., Schumann, G., Fornage, M., Franke, B., Debette, S., Medland, S.E., Ikram, M.A., Thompson, P.M., Adams, H.H.H., Hibar, D.P., Chouraki, V., Stein, J.L., Nyquist, P.A., Renteria, M.E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A.H., Jahanshad, N., Wittfeld, K., van der Lee, S.J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beiser, A., Bernard, M., Bis, J.C., Blanken, L.M.E., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chauhan, G., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., Braber, A.D., Doan, N.T., Ehrlich, S., Filippi, I., Ge, T., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Greven, C.U., Grimm, O., Griswold, M.E., Guadalupe, T., Hass, J., Haukvik, U.K., Hilal, S., Hofer, E., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liao, J., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A., Matarin, M., Mather, K.A., Mattheisen, M., Mazoyer, B., McKay, D.R., McWhirter, R., Milaneschi, Y., Mirza-Schreiber, N., Muetzel, R.L., Maniega, S.M., Nho, K., Nugent, A.C., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pappa, I., Pirpamer, L., Pudas, S., Pütz, B., Rajan, K.B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Thomson, R., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Vaidya, D., Van der Grond, J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Woldehawariat, G., Wolf, C., Wolfers, T., Xu, B., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Aggarwal, N.T., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Chen, C., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., De Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Erk, S., Espeseth, T., Evans, D.A., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Grabe, H.J., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Pol, H.E.H., Ikeda, M., Ikram, M.K., Jack, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Longstreth, W.T., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, K.L., McMahon, F.J., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schofield, P.R., Sigurdsson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Srikanth, V., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Tiemeier, H., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., Van der Lugt, A., van der Wee, N.J.A., van Duijn, C.M., van Haren, N.E.M., Van′t Ent, D., van Tol, M-J, Vardarajan, B.N., Veltman, D.J., Vernooij, M.W., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, H.R., Zonderman, A.B., Deary, I.J., DeCarli, C., Schmidt, H., Martin, N.G., de Craen, A.J.M., Wright, M.J., Launer, L.J., Schumann, G., Fornage, M., Franke, B., Debette, S., Medland, S.E., Ikram, M.A., and Thompson, P.M.
Abstract: Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
Published: 2016

26. P.031 Lemierre’s syndrome - a rare disease with devastating complications

Author: Alhusaini, S, primary, Althubait, S, additional, Melmed, C, additional, and Sidel, M, additional
Published: 2016
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27. The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data

Author: Thompson, PM, Stein, JL, Medland, SE, Hibar, DP, Vasquez, AA, Renteria, ME, Toro, R, Jahanshad, N, Schumann, G, Franke, B, Wright, MJ, Martin, NG, Agartz, I, Alda, M, Alhusaini, S, Almasy, L, Almeida, J, Alpert, K, Andreasen, NC, Andreassen, OA, Apostolova, LG, Appel, K, Armstrong, NJ, Aribisala, B, Bastin, ME, Bauer, M, Bearden, CE, Bergmann, Ø, Binder, EB, Blangero, J, Bockholt, HJ, Bøen, E, Bois, C, Boomsma, DI, Booth, T, Bowman, IJ, Bralten, J, Brouwer, RM, Brunner, HG, Brohawn, DG, Buckner, RL, Buitelaar, J, Bulayeva, K, Bustillo, JR, Calhoun, VD, Cannon, DM, Cantor, RM, Carless, MA, Caseras, X, Cavalleri, GL, Chakravarty, MM, Chang, KD, Ching, CRK, Christoforou, A, Cichon, S, Clark, VP, Conrod, P, Coppola, G, Crespo-Facorro, B, Curran, JE, Czisch, M, Deary, IJ, de Geus, EJC, den Braber, A, Delvecchio, G, Depondt, C, de Haan, L, de Zubicaray, GI, Dima, D, Dimitrova, R, and Djurovic, S
Subjects: endocrine system
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. © 2014 The Author(s).
Published: 2014
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28. Common genetic variants influence human subcortical brain structures

Author: Hibar, DP, Stein, JL, Renteria, ME, Arias-Vasquez, A, Desrivières, S, Jahanshad, N, Toro, R, Wittfeld, K, Abramovic, L, Andersson, M, Aribisala, BS, Armstrong, NJ, Bernard, M, Bohlken, MM, Boks, MP, Bralten, J, Brown, AA, Mallar Chakravarty, M, Chen, Q, Ching, CRK, Cuellar-Partida, G, Den Braber, A, Giddaluru, S, Goldman, AL, Grimm, O, Guadalupe, T, Hass, J, Woldehawariat, G, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Kim, S, Klein, M, Kraemer, B, Lee, PH, Olde Loohuis, LM, Luciano, M, MacAre, C, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Mattheisen, M, Milaneschi, Y, Nho, K, Papmeyer, M, Ramasamy, A, Risacher, SL, Roiz-Santiañez, R, Rose, EJ, Salami, A, Sämann, PG, Schmaal, L, Schork, AJ, Shin, J, Strike, LT, Teumer, A, Van Donkelaar, MMJ, Van Eijk, KR, Walters, RK, Westlye, LT, Whelan, CD, Winkler, AM, Zwiers, MP, Alhusaini, S, Athanasiu, L, Ehrlich, S, Hakobjan, MMH, Hartberg, CB, Haukvik, UK, Heister, AJGAM, Hoehn, D, Kasperaviciute, D, Liewald, DCM, Lopez, LM, Makkinje, RRR, Matarin, M, Naber, MAM, Reese McKay, D, Needham, M, Nugent, AC, Pütz, B, Royle, NA, Shen, L, Sprooten, E, Trabzuni, D, Van Der Marel, SSL, Van Hulzen, KJE, Walton, E, Wolf, C, Almasy, L, Ames, D, Arepalli, S, Assareh, AA, Bastin, ME, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Bulayeva, KB, Carless, MA, Cichon, S, Corvin, A, Curran, JE, Czisch, M, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Wen, Wei ; https://orcid.org/0000-0003-2753-3870, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Thalamuthu, Anbu ; https://orcid.org/0000-0002-7114-1260, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, Schofield, Peter, Hibar, DP, Stein, JL, Renteria, ME, Arias-Vasquez, A, Desrivières, S, Jahanshad, N, Toro, R, Wittfeld, K, Abramovic, L, Andersson, M, Aribisala, BS, Armstrong, NJ, Bernard, M, Bohlken, MM, Boks, MP, Bralten, J, Brown, AA, Mallar Chakravarty, M, Chen, Q, Ching, CRK, Cuellar-Partida, G, Den Braber, A, Giddaluru, S, Goldman, AL, Grimm, O, Guadalupe, T, Hass, J, Woldehawariat, G, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Kim, S, Klein, M, Kraemer, B, Lee, PH, Olde Loohuis, LM, Luciano, M, MacAre, C, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Mattheisen, M, Milaneschi, Y, Nho, K, Papmeyer, M, Ramasamy, A, Risacher, SL, Roiz-Santiañez, R, Rose, EJ, Salami, A, Sämann, PG, Schmaal, L, Schork, AJ, Shin, J, Strike, LT, Teumer, A, Van Donkelaar, MMJ, Van Eijk, KR, Walters, RK, Westlye, LT, Whelan, CD, Winkler, AM, Zwiers, MP, Alhusaini, S, Athanasiu, L, Ehrlich, S, Hakobjan, MMH, Hartberg, CB, Haukvik, UK, Heister, AJGAM, Hoehn, D, Kasperaviciute, D, Liewald, DCM, Lopez, LM, Makkinje, RRR, Matarin, M, Naber, MAM, Reese McKay, D, Needham, M, Nugent, AC, Pütz, B, Royle, NA, Shen, L, Sprooten, E, Trabzuni, D, Van Der Marel, SSL, Van Hulzen, KJE, Walton, E, Wolf, C, Almasy, L, Ames, D, Arepalli, S, Assareh, AA, Bastin, ME, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Bulayeva, KB, Carless, MA, Cichon, S, Corvin, A, Curran, JE, Czisch, M, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Wen, Wei ; https://orcid.org/0000-0003-2753-3870, Kwok, John ; https://orcid.org/0000-0001-9574-6195, Thalamuthu, Anbu ; https://orcid.org/0000-0002-7114-1260, Reppermund, Simone ; https://orcid.org/0000-0003-4785-0224, and Schofield, Peter
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08×10 -33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
Published: 2015

29. Common genetic variants influence human subcortical brain structures

Author: Hibar, D.P. (Derrek), Stein, J.L., Rentería, M.E. (Miguel), Arias-Vásquez, A. (Alejandro), Desrivières, S. (Sylvane), Jahanshad, N. (Neda), Toro, R. (Roberto), Wittfeld, K. (Katharina), Abramovic, L. (Lucija), Andersson, M. (Micael), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Bernard, M. (Manon), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brown, A.A. (Andrew), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Cuellar-Partida, G. (Gabriel), Braber, A. (Anouk) den, Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Grimm, O. (Oliver), Guadalupe, T. (Tulio), Hass, J. (Johanna), Woldehawariat, G. (Girma), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil H.), Olde Loohuis, L.M. (Loes M.), Luciano, M. (Michelle), MacAre, C. (Christine), Mather, R., Mattheisen, M. (Manuel), Milaneschi, Y. (Yuri), Nho, K. (Kwangsik), Papmeyer, M. (Martina), Ramasamy, A. (Adaikalavan), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rose, E.J. (Emma), Salami, A. (Alireza), Sämann, P.G. (Philipp), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shin, J. (Jean), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Walters, R.K. (Raymond), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Winkler, A.M. (Anderson), Zwiers, M.P. (Marcel), Alhusaini, S. (Saud), Athanasiu, L. (Lavinia), Ehrlich, S.M. (Stefan), Hakobjan, M. (Marina), Hartberg, C.B. (Cecilie B.), Haukvik, U.K. (Unn), Heister, A.J.G.A.M. (Angelien J. G. A. M.), Hoehn, D. (David), Kasperaviciute, D. (Dalia), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Makkinje, R.R.R. (Remco R. R.), Matarin, M. (Mar), Naber, M.A.M. (Marlies A. M.), McKay, D.R. (Reese), Needham, M. (Margaret), Nugent, A.C. (Allison), Pütz, B. (Benno), Royle, N.A. (Natalie), Shen, L. (Li), Sprooten, R. (Roy), Trabzuni, D. (Danyah), Van Der Marel, S.S.L. (Saskia S. L.), Van Hulzen, K.J.E. (Kimm J. E.), Walton, E. (Esther), Björnsson, A. (Asgeir), Almasy, L. (Laura), Ames, D.J. (David), Arepalli, S. (Sampath), Assareh, A.A., Bastin, M.E. (Mark), Brodaty, H. (Henry), Bulayeva, K. (Kazima), Carless, M.A. (Melanie), Cichon, S. (Sven), Corvin, A. (Aiden), Curran, J.E. (Joanne), Czisch, M. (Michael), Zubicaray, G.I. (Greig) de, Dillman, A. (Allissa), Duggirala, A. (Aparna), Dyer, M.D. (Matthew), Erk, S., Fedko, I. (Iryna), Ferrucci, L. (Luigi), Foroud, T. (Tatiana), Fox, P.T. (Peter), Fukunaga, M. (Masaki), Raphael Gibbs, J., Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Guelfi, S. (Sebastian), Hansell, N.K. (Narelle), Hartman, C.A. (Catharina), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Hoekstra, P.J. (Pieter), Holsboer, F., Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Ikeda, M. (Masashi), Jack Jr., C.R. (Clifford), Jenkinson, S. (Sarah), Johnson, R. (Robert), Kanai, R. (Ryota), Keil, M. (Maria), Kent, J.W. (Jack W.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Mcmahon, K.L. (Katie), Meisenzahl, E. (Eva), Melle, I. (Ingrid), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant), Mostert, J.C. (Jeanette C.), Mühleisen, T.W. (Thomas), Nalls, M.A. (Michael), Nichols, T.E. (Thomas), Nilsson, L.G., Nöthen, M.M. (Markus), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Perez-Iglesias, R. (Rocio), Pike, G.B. (Bruce), Potkin, S.G. (Steven), Reinvang, I. (Ivar), Reppermund, S., Rietschel, M. (Marcella), Seiferth, N. (Nina), Rosen, G.D. (Glenn D.), Rujescu, D. (Dan), Schnell, K. (Kerry), Schofield, C.J. (Christopher), Smith, C. (Colin), Steen, V.M. (Vidar), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Turner, J. (Jessica), Valdés Hernández, M.C. (Maria), Ent, D. (Dennis) van 't, Brug, M.P. (Marcel) van der, Wee, N.J. (Nic) van der, Tol, M.J.D. (Marie-José) van, Veltman, D.J. (Dick), Wassink, A.M.J. (Annemarie), Westman, E. (Eric), Zielke, R.H. (Ronald H.), Zonderman, A.B. (Alan B.), Ashbrook, D.G. (David G.), Hager, R. (Reinmar), Lu, L. (Lu), Mcmahon, F.J. (Francis J), Morris, D.W. (Derek W), Williams, R.W. (Robert W.), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan K.), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cavalleri, G. (Gianpiero), Crespo-Facorro, B. (Benedicto), Dale, A.M. (Anders), Davies, G.E. (Gareth), Delanty, N., Depondt, C. (Chantal), Djurovic, S. (Srdjan), Drevets, D.A. (Douglas), Espeseth, T. (Thomas), Gollub, R.L. (Randy), Ho, B.C. (Beng ), Hoffmann, W. (Wolfgang), Hosten, N. (Norbert), Kahn, R. (René), Le Hellard, S. (Stephanie), Meyer-Lindenberg, A., Müller-Myhsok, B. (B.), Nauck, M. (Matthias), Nyberg, L. (Lars), Pandolfo, M. (Massimo), Penninx, B.W.J.H. (Brenda), Roffman, J.L. (Joshua), Sisodiya, S.M. (Sanjay), Smoller, J.W., Bokhoven, H. (Hans) van, Haren, N.E.M. (Neeltje E.) van, Völzke, H. (Henry), Walter, H.J. (Henrik), Weiner, M.W. (Michael), Wen, W. (Wei), White, T.J.H. (Tonya), Agartz, I. (Ingrid), Andreassen, O.A. (Ole), Blangero, J. (John), Boomsma, D.I. (Dorret), Brouwer, R.M. (Rachel), Cannon, D.M. (Dara), Cookson, M.R. (Mark), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Donohoe, D.J. (Dennis), Fernandez, G. (Guillén), Fisher, S.E. (Simon), Francks, C. (Clyde), Glahn, D.C. (David), Grabe, H.J. (Hans Jörgen), Gruber, O. (Oliver), Hardy, J. (John), Hashimoto, R. (Ryota), Hulshoff Pol, H.E. (Hilleke), Jönsson, E.G. (Erik), Kloszewska, I. (Iwona), Lovestone, S. (Simon), Mattay, V.S. (Venkata S.), Mecocci, P. (Patrizia), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Ophoff, R.A. (Roel), Paus, T. (Tomas), Pausova, Z. (Zdenka), Ryten, M. (Mina), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Simmons, A. (Andrew), Singleton, A. (Andrew), Soininen, H. (H.), Wardlaw, J.M. (J.), Weale, M.E. (Michael), Weinberger, D.R. (Daniel), Adams, H.H.H. (Hieab), Launer, L.J. (Lenore), Seiler, S. (Stephan), Schmidt, R. (Reinhold), Chauhan, G. (Ganesh), Satizabal, C.L. (Claudia), Becker, J.T. (James), Yanek, L.R. (Lisa), Lee, S.J. (Sven) van der, Ebling, M. (Maritza), Fischl, B. (Bruce), Longstreth Jr, W.T., Greve, D. (Douglas), Nyquist, P. (Paul), Vinke, L.N. (Louis N.), Duijn, C.M. (Cornelia) van, Xue, L. (Luting), Mazoyer, B. (Bernard), Bis, J.C. (Joshua), Gudnason, V. (Vilmundur), Seshadri, S. (Sudha), Ikram, M.A. (Arfan), Martin, N.G. (Nicholas), Wright, M.J. (Margaret), Schumann, G. (Gunter), Franke, B. (Barbara), Thompson, P.M. (Paul), Medland, S.E. (Sarah), Hibar, D.P. (Derrek), Stein, J.L., Rentería, M.E. (Miguel), Arias-Vásquez, A. (Alejandro), Desrivières, S. (Sylvane), Jahanshad, N. (Neda), Toro, R. (Roberto), Wittfeld, K. (Katharina), Abramovic, L. (Lucija), Andersson, M. (Micael), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Bernard, M. (Manon), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brown, A.A. (Andrew), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Cuellar-Partida, G. (Gabriel), Braber, A. (Anouk) den, Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Grimm, O. (Oliver), Guadalupe, T. (Tulio), Hass, J. (Johanna), Woldehawariat, G. (Girma), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil H.), Olde Loohuis, L.M. (Loes M.), Luciano, M. (Michelle), MacAre, C. (Christine), Mather, R., Mattheisen, M. (Manuel), Milaneschi, Y. (Yuri), Nho, K. (Kwangsik), Papmeyer, M. (Martina), Ramasamy, A. (Adaikalavan), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rose, E.J. (Emma), Salami, A. (Alireza), Sämann, P.G. (Philipp), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shin, J. (Jean), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Walters, R.K. (Raymond), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Winkler, A.M. (Anderson), Zwiers, M.P. (Marcel), Alhusaini, S. (Saud), Athanasiu, L. (Lavinia), Ehrlich, S.M. (Stefan), Hakobjan, M. (Marina), Hartberg, C.B. (Cecilie B.), Haukvik, U.K. (Unn), Heister, A.J.G.A.M. (Angelien J. G. A. M.), Hoehn, D. (David), Kasperaviciute, D. (Dalia), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Makkinje, R.R.R. (Remco R. R.), Matarin, M. (Mar), Naber, M.A.M. (Marlies A. M.), McKay, D.R. (Reese), Needham, M. (Margaret), Nugent, A.C. (Allison), Pütz, B. (Benno), Royle, N.A. (Natalie), Shen, L. (Li), Sprooten, R. (Roy), Trabzuni, D. (Danyah), Van Der Marel, S.S.L. (Saskia S. L.), Van Hulzen, K.J.E. (Kimm J. E.), Walton, E. (Esther), Björnsson, A. (Asgeir), Almasy, L. (Laura), Ames, D.J. (David), Arepalli, S. (Sampath), Assareh, A.A., Bastin, M.E. (Mark), Brodaty, H. (Henry), Bulayeva, K. (Kazima), Carless, M.A. (Melanie), Cichon, S. (Sven), Corvin, A. (Aiden), Curran, J.E. (Joanne), Czisch, M. (Michael), Zubicaray, G.I. (Greig) de, Dillman, A. (Allissa), Duggirala, A. (Aparna), Dyer, M.D. (Matthew), Erk, S., Fedko, I. (Iryna), Ferrucci, L. (Luigi), Foroud, T. (Tatiana), Fox, P.T. (Peter), Fukunaga, M. (Masaki), Raphael Gibbs, J., Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Guelfi, S. (Sebastian), Hansell, N.K. (Narelle), Hartman, C.A. (Catharina), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Hoekstra, P.J. (Pieter), Holsboer, F., Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Ikeda, M. (Masashi), Jack Jr., C.R. (Clifford), Jenkinson, S. (Sarah), Johnson, R. (Robert), Kanai, R. (Ryota), Keil, M. (Maria), Kent, J.W. (Jack W.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Mcmahon, K.L. (Katie), Meisenzahl, E. (Eva), Melle, I. (Ingrid), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant), Mostert, J.C. (Jeanette C.), Mühleisen, T.W. (Thomas), Nalls, M.A. (Michael), Nichols, T.E. (Thomas), Nilsson, L.G., Nöthen, M.M. (Markus), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Perez-Iglesias, R. (Rocio), Pike, G.B. (Bruce), Potkin, S.G. (Steven), Reinvang, I. (Ivar), Reppermund, S., Rietschel, M. (Marcella), Seiferth, N. (Nina), Rosen, G.D. (Glenn D.), Rujescu, D. (Dan), Schnell, K. (Kerry), Schofield, C.J. (Christopher), Smith, C. (Colin), Steen, V.M. (Vidar), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Turner, J. (Jessica), Valdés Hernández, M.C. (Maria), Ent, D. (Dennis) van 't, Brug, M.P. (Marcel) van der, Wee, N.J. (Nic) van der, Tol, M.J.D. (Marie-José) van, Veltman, D.J. (Dick), Wassink, A.M.J. (Annemarie), Westman, E. (Eric), Zielke, R.H. (Ronald H.), Zonderman, A.B. (Alan B.), Ashbrook, D.G. (David G.), Hager, R. (Reinmar), Lu, L. (Lu), Mcmahon, F.J. (Francis J), Morris, D.W. (Derek W), Williams, R.W. (Robert W.), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan K.), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cavalleri, G. (Gianpiero), Crespo-Facorro, B. (Benedicto), Dale, A.M. (Anders), Davies, G.E. (Gareth), Delanty, N., Depondt, C. (Chantal), Djurovic, S. (Srdjan), Drevets, D.A. (Douglas), Espeseth, T. (Thomas), Gollub, R.L. (Randy), Ho, B.C. (Beng ), Hoffmann, W. (Wolfgang), Hosten, N. (Norbert), Kahn, R. (René), Le Hellard, S. (Stephanie), Meyer-Lindenberg, A., Müller-Myhsok, B. (B.), Nauck, M. (Matthias), Nyberg, L. (Lars), Pandolfo, M. (Massimo), Penninx, B.W.J.H. (Brenda), Roffman, J.L. (Joshua), Sisodiya, S.M. (Sanjay), Smoller, J.W., Bokhoven, H. (Hans) van, Haren, N.E.M. (Neeltje E.) van, Völzke, H. (Henry), Walter, H.J. (Henrik), Weiner, M.W. (Michael), Wen, W. (Wei), White, T.J.H. (Tonya), Agartz, I. (Ingrid), Andreassen, O.A. (Ole), Blangero, J. (John), Boomsma, D.I. (Dorret), Brouwer, R.M. (Rachel), Cannon, D.M. (Dara), Cookson, M.R. (Mark), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Donohoe, D.J. (Dennis), Fernandez, G. (Guillén), Fisher, S.E. (Simon), Francks, C. (Clyde), Glahn, D.C. (David), Grabe, H.J. (Hans Jörgen), Gruber, O. (Oliver), Hardy, J. (John), Hashimoto, R. (Ryota), Hulshoff Pol, H.E. (Hilleke), Jönsson, E.G. (Erik), Kloszewska, I. (Iwona), Lovestone, S. (Simon), Mattay, V.S. (Venkata S.), Mecocci, P. (Patrizia), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Ophoff, R.A. (Roel), Paus, T. (Tomas), Pausova, Z. (Zdenka), Ryten, M. (Mina), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Simmons, A. (Andrew), Singleton, A. (Andrew), Soininen, H. (H.), Wardlaw, J.M. (J.), Weale, M.E. (Michael), Weinberger, D.R. (Daniel), Adams, H.H.H. (Hieab), Launer, L.J. (Lenore), Seiler, S. (Stephan), Schmidt, R. (Reinhold), Chauhan, G. (Ganesh), Satizabal, C.L. (Claudia), Becker, J.T. (James), Yanek, L.R. (Lisa), Lee, S.J. (Sven) van der, Ebling, M. (Maritza), Fischl, B. (Bruce), Longstreth Jr, W.T., Greve, D. (Douglas), Nyquist, P. (Paul), Vinke, L.N. (Louis N.), Duijn, C.M. (Cornelia) van, Xue, L. (Luting), Mazoyer, B. (Bernard), Bis, J.C. (Joshua), Gudnason, V. (Vilmundur), Seshadri, S. (Sudha), Ikram, M.A. (Arfan), Martin, N.G. (Nicholas), Wright, M.J. (Margaret), Schumann, G. (Gunter), Franke, B. (Barbara), Thompson, P.M. (Paul), and Medland, S.E. (Sarah)
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, a
Published: 2015
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30. Common genetic variants influence human subcortical brain structures

Author: Hibar, D.P., Stein, J.L., Renteria, M.E., Arias-Vasquez, A., Desrivières, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J., Brown, A.A., Mallar Chakravarty, M., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., den Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santiañez, R., Rose, E.J., Salami, A., Sämann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., van Donkelaar, M.M.J., van Eijk, K.R., Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M.H., Hartberg, C.B., Haukvik, U.K., Heister, A.J.G.A.M., Hoehn, D., Kasperaviciute, D., Liewald, D.C.M., Lopez, L.M., Makkinje, R.R.R., Matarin, M., Naber, M.A.M., Reese McKay, D., Needham, M., Nugent, A.C., Pütz, B., Royle, N.A., Shen, Li, Sprooten, E., Trabzuni, D., van der Marel, S.S.L., van Hulzen, K.J.E., Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., de Zubicaray, G.I., Dillman, A., Duggirala, R., Dyer, T.D., Erk, S., Fedko, I.O., Ferrucci, L., Foroud, T.M., Fox, P.T., Fukunaga, M., Raphael Gibbs, J., Göring, H.H.H., Green, R.C., Guelfi, S., Hansell, N.K., Hartman, C.A., Hegenscheid, K., Heinz, A., Hernandez, D.G., Heslenfeld, D.J., Hoekstra, P.J., Holsboer, F., Homuth, G., Hottenga, J-J, Ikeda, M., Jack, C.R., Jenkinson, M., Johnson, R., Kanai, R., Keil, M., Kent, J.W., Kochunov, P., Kwok, J.B., Lawrie, S.M., Liu, X., Longo, D.L., McMahon, K.L., Meisenzahl, E., Melle, I., Mohnke, S., Montgomery, G.W., Mostert, J.C., Mühleisen, T.W., Nalls, M.A., Nichols, T.E., Nilsson, L.G., Nöthen, M.M., Ohi, K., Olvera, R.L., Perez-Iglesias, R., Bruce Pike, G., Potkin, S.G., Reinvang, I., Reppermund, S., Rietschel, M., Romanczuk-Seiferth, N., Rosen, G.D., Rujescu, D., Schnell, K., Schofield, P.R., Smith, C., Steen, V.M., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Valdés Hernández, M.C., van 't Ent, D., van der Brug, M., van der Wee, N.J.A., van Tol, M-J, Veltman, D.J., Wassink, T.H., Westman, E., Zielke, R.H., Zonderman, A.B., Ashbrook, D.G., Hager, R., Lu, L., McMahon, F.J., Morris, D.W., Williams, R.W., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Cahn, W., Calhoun, V.D., Cavalleri, G.L., Crespo-Facorro, B., Dale, A.M., Davies, G.E., Delanty, N., Depondt, C., Djurovic, S., Drevets, W.C., Espeseth, T., Gollub, R.L., Ho, B-C., Hoffmann, W., Hosten, N., Kahn, R.S., Le Hellard, S., Meyer-Lindenberg, A., Müller-Myhsok, B., Nauck, M., Nyberg, L., Pandolfo, M., Penninx, B.W.J.H., Roffman, J.L., Sisodiya, S.M., Smoller, J.W., van Bokhoven, H., van Haren, N.E.M., Völzke, H., Walter, H., Weiner, M.W., Wen, W., White, T., Agartz, I., Andreassen, O.A., Blangero, J., Boomsma, D.I., Brouwer, R.M., Cannon, D.M., Cookson, M.R., de Geus, E.J.C., Deary, I.J., Donohoe, G., Fernández, G., Fisher, S.E., Francks, C., Glahn, D.C., Grabe, H.J., Gruber, O., Hardy, J., Hashimoto, R., Hulshoff Pol, H.E., Jönsson, E.G., Kloszewska, I., Lovestone, S., Mattay, V.S., Mecocci, P., McDonald, C., McIntosh, A.M., Ophoff, R.A., Paus, T., Pausova, Z., Ryten, M., Sachdev, P.S., Saykin, A.J., Simmons, A., Singleton, A., Soininen, H., Wardlaw, J.M., Weale, M.E., Weinberger, D.R., Adams, H.H.H., Launer, L.J., Seiler, S., Schmidt, R., Chauhan, G., Satizabal, C.L., Becker, J.T., Yanek, L., van der Lee, S.J., Ebling, M., Fischl, B., Longstreth, W.T., Greve, D., Schmidt, H., Nyquist, P., Vinke, L.N., van Duijn, C.M., Xue, L., Mazoyer, B., Bis, J.C., Gudnason, V., Seshadri, S., Ikram, M.A., Martin, N.G., Wright, M.J., Schumann, G., Franke, B., Thompson, P.M., Medland, S.E., Hibar, D.P., Stein, J.L., Renteria, M.E., Arias-Vasquez, A., Desrivières, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J., Brown, A.A., Mallar Chakravarty, M., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., den Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santiañez, R., Rose, E.J., Salami, A., Sämann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., van Donkelaar, M.M.J., van Eijk, K.R., Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M.H., Hartberg, C.B., Haukvik, U.K., Heister, A.J.G.A.M., Hoehn, D., Kasperaviciute, D., Liewald, D.C.M., Lopez, L.M., Makkinje, R.R.R., Matarin, M., Naber, M.A.M., Reese McKay, D., Needham, M., Nugent, A.C., Pütz, B., Royle, N.A., Shen, Li, Sprooten, E., Trabzuni, D., van der Marel, S.S.L., van Hulzen, K.J.E., Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., de Zubicaray, G.I., Dillman, A., Duggirala, R., Dyer, T.D., Erk, S., Fedko, I.O., Ferrucci, L., Foroud, T.M., Fox, P.T., Fukunaga, M., Raphael Gibbs, J., Göring, H.H.H., Green, R.C., Guelfi, S., Hansell, N.K., Hartman, C.A., Hegenscheid, K., Heinz, A., Hernandez, D.G., Heslenfeld, D.J., Hoekstra, P.J., Holsboer, F., Homuth, G., Hottenga, J-J, Ikeda, M., Jack, C.R., Jenkinson, M., Johnson, R., Kanai, R., Keil, M., Kent, J.W., Kochunov, P., Kwok, J.B., Lawrie, S.M., Liu, X., Longo, D.L., McMahon, K.L., Meisenzahl, E., Melle, I., Mohnke, S., Montgomery, G.W., Mostert, J.C., Mühleisen, T.W., Nalls, M.A., Nichols, T.E., Nilsson, L.G., Nöthen, M.M., Ohi, K., Olvera, R.L., Perez-Iglesias, R., Bruce Pike, G., Potkin, S.G., Reinvang, I., Reppermund, S., Rietschel, M., Romanczuk-Seiferth, N., Rosen, G.D., Rujescu, D., Schnell, K., Schofield, P.R., Smith, C., Steen, V.M., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Valdés Hernández, M.C., van 't Ent, D., van der Brug, M., van der Wee, N.J.A., van Tol, M-J, Veltman, D.J., Wassink, T.H., Westman, E., Zielke, R.H., Zonderman, A.B., Ashbrook, D.G., Hager, R., Lu, L., McMahon, F.J., Morris, D.W., Williams, R.W., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Cahn, W., Calhoun, V.D., Cavalleri, G.L., Crespo-Facorro, B., Dale, A.M., Davies, G.E., Delanty, N., Depondt, C., Djurovic, S., Drevets, W.C., Espeseth, T., Gollub, R.L., Ho, B-C., Hoffmann, W., Hosten, N., Kahn, R.S., Le Hellard, S., Meyer-Lindenberg, A., Müller-Myhsok, B., Nauck, M., Nyberg, L., Pandolfo, M., Penninx, B.W.J.H., Roffman, J.L., Sisodiya, S.M., Smoller, J.W., van Bokhoven, H., van Haren, N.E.M., Völzke, H., Walter, H., Weiner, M.W., Wen, W., White, T., Agartz, I., Andreassen, O.A., Blangero, J., Boomsma, D.I., Brouwer, R.M., Cannon, D.M., Cookson, M.R., de Geus, E.J.C., Deary, I.J., Donohoe, G., Fernández, G., Fisher, S.E., Francks, C., Glahn, D.C., Grabe, H.J., Gruber, O., Hardy, J., Hashimoto, R., Hulshoff Pol, H.E., Jönsson, E.G., Kloszewska, I., Lovestone, S., Mattay, V.S., Mecocci, P., McDonald, C., McIntosh, A.M., Ophoff, R.A., Paus, T., Pausova, Z., Ryten, M., Sachdev, P.S., Saykin, A.J., Simmons, A., Singleton, A., Soininen, H., Wardlaw, J.M., Weale, M.E., Weinberger, D.R., Adams, H.H.H., Launer, L.J., Seiler, S., Schmidt, R., Chauhan, G., Satizabal, C.L., Becker, J.T., Yanek, L., van der Lee, S.J., Ebling, M., Fischl, B., Longstreth, W.T., Greve, D., Schmidt, H., Nyquist, P., Vinke, L.N., van Duijn, C.M., Xue, L., Mazoyer, B., Bis, J.C., Gudnason, V., Seshadri, S., Ikram, M.A., Martin, N.G., Wright, M.J., Schumann, G., Franke, B., Thompson, P.M., and Medland, S.E.
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
Published: 2015

31. The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data

Author: Thompson, P.M. (Paul), Stein, J.L., Medland, S.E. (Sarah), Hibar, D.P. (Derrek), Vásquez, A.A. (Arias), Rentería, M.E. (Miguel), Toro, R. (Roberto), Jahanshad, N. (Neda), Schumann, G. (Gunter), Franke, B. (Barbara), Wright, M.J. (Margaret), Martin, N.G. (Nicholas), Agartz, I. (Ingrid), Alda, M. (Martin), Alhusaini, S. (Saud), Almasy, L. (Laura), Alpert, K. (Kathryn), Andreasen, N.C., Andreassen, O.A. (Ole), Apostolova, L.G. (Liana), Appel, K. (Katja), Armstrong, N.J. (Nicola), Aribisala, B. (Benjamin), Bastin, M.E. (Mark), Bauer, M. (Michael), Bearden, C.E. (Carrie), Bergmann, Ø. (Ørjan), Binder, E.B. (Elisabeth), Blangero, J. (John), Bockholt, H.J., Bøen, E. (Erlend), Bois, M. (Monique), Boomsma, D.I. (Dorret), Booth, T. (Tom), Bowman, I.J. (Ian), Bralten, L.B.C. (Linda), Brouwer, R.M. (Rachel), Brunner, H.G., Brohawn, D.G. (David), Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Bustillo, J., Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cantor, R.M., Carless, M.A. (Melanie), Caseras, X. (Xavier), Cavalleri, G. (Gianpiero), Chakravarty, M.M. (M. Mallar), Chang, K.D. (Kiki), Ching, C.R.K. (Christopher), Christoforou, A. (Andrea), Cichon, S. (Sven), Clark, V.P., Conrod, P. (Patricia), Coppola, D. (Domenico), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Deary, I.J. (Ian), Geus, E.J.C. (Eco) de, Braber, A. (Anouk) den, Delvecchio, G. (Giuseppe), Depondt, C. (Chantal), Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Dima, D. (Danai), Dimitrova, R. (Rali), Djurovic, S. (Srdjan), Dong, H. (Hongwei), Donohoe, D.J. (Dennis), Duggirala, A. (Aparna), Dyer, M.D. (Matthew), Ehrlich, S.M. (Stefan), Ekman, C.J. (Carl Johan), Elvsåshagen, T. (Torbjørn), Emsell, L. (Louise), Erk, S., Espeseth, T. (Thomas), Fagerness, J. (Jesen), Fears, S. (Scott), Fedko, I. (Iryna), Fernandez, G. (Guillén), Fisher, S.E. (Simon), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Frangou, S. (Sophia), Frey, E.M. (Eva Maria), Frodl, T. (Thomas), Frouin, V. (Vincent), Garavan, H. (Hugh), Giddaluru, S. (Sudheer), Glahn, D.C. (David), Godlewska, B. (Beata), Goldstein, R.Z. (Rita), Gollub, R.L. (Randy), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Gruber, O. (Oliver), Guadalupe, T. (Tulio), Gur, R.E. (Raquel), Gur, R.C. (Ruben), Göring, H.H.H. (Harald), Hagenaars, S. (Saskia), Hajek, T. (Tomas), Hall, G.B. (Garry), Hall, J. (Jeremy), Hardy, J. (John), Hartman, C.A. (Catharina), Hass, J. (Johanna), Hatton, W., Haukvik, U.K. (Unn), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Hickie, I.B. (Ian), Ho, B.C. (Beng ), Hoehn, D. (David), Hoekstra, P.J. (Pieter), Hollinshead, M. (Marisa), Holmes, A.J. (Avram), Homuth, G. (Georg), Hoogman, M. (Martine), Hong, L.E. (L.Elliot), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Hulshoff Pol, H.E. (Hilleke), Hwang, K.S. (Kristy), Jack Jr., C.R. (Clifford), Jenkinson, S. (Sarah), Johnston, C., Jönsson, E.G. (Erik), Kahn, R.S. (René), Kasperaviciute, D. (Dalia), Kelly, S. (Steve), Kim, S. (Shinseog), Kochunov, P. (Peter), Koenders, L. (Laura), Krämer, B. (Bernd), Kwok, J.B.J. (John), Lagopoulos, J. (Jim), Laje, G. (Gonzalo), Landén, M. (Mikael), Landman, B.A. (Bennett), Lauriello, J., Lawrie, S. (Stephen), Lee, P.H. (Phil), Le Hellard, S. (Stephanie), Lemaître, H. (Herve), Leonardo, C.D. (Cassandra), Li, C.-S. (Chiang-shan), Liberg, B. (Benny), Liewald, D.C.M. (David), Liu, X. (Xinmin), Lopez, L.M. (Lorna), Loth, E. (Eva), Lourdusamy, A. (Anbarasu), Luciano, M. (Michelle), MacCiardi, F. (Fabio), Machielsen, M.W.J. (Marise), MacQueen, G.M. (Glenda), Malt, U.F. (Ulrik), Mandl, R. (René), Manoach, D.S. (Dara), Martinot, J.-L. (Jean-Luc), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), Meyer-Lindenberg, A., McDonald, C. (Colm), McIntosh, A.M. (Andrew), Mcmahon, F.J. (Francis J), Mcmahon, K.L. (Katie), Meisenzahl, E. (Eva), Melle, I. (Ingrid), Milaneschi, Y. (Yuri), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant), Morris, D.W. (Derek W), Moses, E.K. (Eric), Mueller, B.A. (Bryon ), Muñoz Maniega, S. (Susana), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (Bertram), Mwangi, B. (Benson), Nauck, M. (Matthias), Nho, K. (Kwangsik), Nichols, T.E. (Thomas), Nilsson, L.G., Nugent, A.C. (Allison), Nyberg, L. (Lisa), Olvera, R.L. (Rene), Oosterlaan, J. (Jaap), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Papalampropoulou-Tsiridou, M. (Melina), Papmeyer, M. (Martina), Paus, T. (Tomas), Pausova, Z. (Zdenka), Pearlson, G. (Godfrey), Penninx, B.W.J.H. (Brenda), Peterson, C.P. (Charles), Pfennig, A. (Andrea), Phillips, M. (Mary), Pike, G.B. (G Bruce), Poline, J.B. (Jean Baptiste), Potkin, S.G. (Steven), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Rasmussen, J. (Jerod), Rietschel, M. (Marcella), Rijpkema, M. (Mark), Risacher, S.L. (Shannon), Roffman, J.L. (Joshua), Roiz-Santiañez, R. (Roberto), Romanczuk-Seiferth, N. (Nina), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rujescu, D. (Dan), Ryten, M. (Mina), Sachdev, P.S. (Perminder), Salami, A. (Alireza), Satterthwaite, T.D. (Theodore), Savitz, J. (Jonathan), Saykin, A.J. (Andrew), Scanlon, C. (Cathy), Schmaal, L. (Lianne), Schnack, H. (Hugo), Schork, N.J. (Nicholas), Schulz, S.C. (S.Charles), Schür, R. (Remmelt), Seidman, L.J. (Larry), Shen, L. (Li), Shoemaker, L. (Lawrence), Simmons, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soares, J.C. (Jair), Sponheim, S.R. (Scott), Sprooten, R. (Roy), Starr, J.M. (John), Steen, V.M. (Vidar), Strakowski, S. (Stephen), Strike, L.T. (Lachlan), Sussmann, J. (Jessika), Sämann, P.G. (Philipp), Teumer, A. (Alexander), Toga, A.W. (Arthur), Tordesillas-Gutierrez, D. (Diana), Trabzuni, D. (Danyah), Trost, S. (Sarah), Turner, J. (Jessica), Heuvel, M. (Martijn) van den, Wee, N.J. (Nic) van der, Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Valdés Hernández, M.C. (Maria), Veltman, D.J. (Dick), Versace, A. (Amelia), Völzke, H. (Henry), Walker, R. (Robert), Walter, H.J. (Henrik), Wang, L. (Lei), Wardlaw, J.M. (J.), Weale, M.E. (Michael), Weiner, M.W. (Michael), Wen, W. (Wei), Westlye, L.T. (Lars), Whalley, H.C. (Heather), Whelan, C.D. (Christopher), White, T.J.H. (Tonya), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Zilles, D. (David), Zwiers, M.P. (Marcel), Thalamuthu, A. (Anbupalam), Almeida, J.R. (Jorge), Schofield, C.J. (Christopher), Freimer, N.B. (Nelson), Lawrence, N.S. (Natalia), Drevets, D.A. (Douglas), Thompson, P.M. (Paul), Stein, J.L., Medland, S.E. (Sarah), Hibar, D.P. (Derrek), Vásquez, A.A. (Arias), Rentería, M.E. (Miguel), Toro, R. (Roberto), Jahanshad, N. (Neda), Schumann, G. (Gunter), Franke, B. (Barbara), Wright, M.J. (Margaret), Martin, N.G. (Nicholas), Agartz, I. (Ingrid), Alda, M. (Martin), Alhusaini, S. (Saud), Almasy, L. (Laura), Alpert, K. (Kathryn), Andreasen, N.C., Andreassen, O.A. (Ole), Apostolova, L.G. (Liana), Appel, K. (Katja), Armstrong, N.J. (Nicola), Aribisala, B. (Benjamin), Bastin, M.E. (Mark), Bauer, M. (Michael), Bearden, C.E. (Carrie), Bergmann, Ø. (Ørjan), Binder, E.B. (Elisabeth), Blangero, J. (John), Bockholt, H.J., Bøen, E. (Erlend), Bois, M. (Monique), Boomsma, D.I. (Dorret), Booth, T. (Tom), Bowman, I.J. (Ian), Bralten, L.B.C. (Linda), Brouwer, R.M. (Rachel), Brunner, H.G., Brohawn, D.G. (David), Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Bustillo, J., Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cantor, R.M., Carless, M.A. (Melanie), Caseras, X. (Xavier), Cavalleri, G. (Gianpiero), Chakravarty, M.M. (M. Mallar), Chang, K.D. (Kiki), Ching, C.R.K. (Christopher), Christoforou, A. (Andrea), Cichon, S. (Sven), Clark, V.P., Conrod, P. (Patricia), Coppola, D. (Domenico), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Deary, I.J. (Ian), Geus, E.J.C. (Eco) de, Braber, A. (Anouk) den, Delvecchio, G. (Giuseppe), Depondt, C. (Chantal), Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Dima, D. (Danai), Dimitrova, R. (Rali), Djurovic, S. (Srdjan), Dong, H. (Hongwei), Donohoe, D.J. (Dennis), Duggirala, A. (Aparna), Dyer, M.D. (Matthew), Ehrlich, S.M. (Stefan), Ekman, C.J. (Carl Johan), Elvsåshagen, T. (Torbjørn), Emsell, L. (Louise), Erk, S., Espeseth, T. (Thomas), Fagerness, J. (Jesen), Fears, S. (Scott), Fedko, I. (Iryna), Fernandez, G. (Guillén), Fisher, S.E. (Simon), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Frangou, S. (Sophia), Frey, E.M. (Eva Maria), Frodl, T. (Thomas), Frouin, V. (Vincent), Garavan, H. (Hugh), Giddaluru, S. (Sudheer), Glahn, D.C. (David), Godlewska, B. (Beata), Goldstein, R.Z. (Rita), Gollub, R.L. (Randy), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Gruber, O. (Oliver), Guadalupe, T. (Tulio), Gur, R.E. (Raquel), Gur, R.C. (Ruben), Göring, H.H.H. (Harald), Hagenaars, S. (Saskia), Hajek, T. (Tomas), Hall, G.B. (Garry), Hall, J. (Jeremy), Hardy, J. (John), Hartman, C.A. (Catharina), Hass, J. (Johanna), Hatton, W., Haukvik, U.K. (Unn), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Hickie, I.B. (Ian), Ho, B.C. (Beng ), Hoehn, D. (David), Hoekstra, P.J. (Pieter), Hollinshead, M. (Marisa), Holmes, A.J. (Avram), Homuth, G. (Georg), Hoogman, M. (Martine), Hong, L.E. (L.Elliot), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Hulshoff Pol, H.E. (Hilleke), Hwang, K.S. (Kristy), Jack Jr., C.R. (Clifford), Jenkinson, S. (Sarah), Johnston, C., Jönsson, E.G. (Erik), Kahn, R.S. (René), Kasperaviciute, D. (Dalia), Kelly, S. (Steve), Kim, S. (Shinseog), Kochunov, P. (Peter), Koenders, L. (Laura), Krämer, B. (Bernd), Kwok, J.B.J. (John), Lagopoulos, J. (Jim), Laje, G. (Gonzalo), Landén, M. (Mikael), Landman, B.A. (Bennett), Lauriello, J., Lawrie, S. (Stephen), Lee, P.H. (Phil), Le Hellard, S. (Stephanie), Lemaître, H. (Herve), Leonardo, C.D. (Cassandra), Li, C.-S. (Chiang-shan), Liberg, B. (Benny), Liewald, D.C.M. (David), Liu, X. (Xinmin), Lopez, L.M. (Lorna), Loth, E. (Eva), Lourdusamy, A. (Anbarasu), Luciano, M. (Michelle), MacCiardi, F. (Fabio), Machielsen, M.W.J. (Marise), MacQueen, G.M. (Glenda), Malt, U.F. (Ulrik), Mandl, R. (René), Manoach, D.S. (Dara), Martinot, J.-L. (Jean-Luc), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), Meyer-Lindenberg, A., McDonald, C. (Colm), McIntosh, A.M. (Andrew), Mcmahon, F.J. (Francis J), Mcmahon, K.L. (Katie), Meisenzahl, E. (Eva), Melle, I. (Ingrid), Milaneschi, Y. (Yuri), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant), Morris, D.W. (Derek W), Moses, E.K. (Eric), Mueller, B.A. (Bryon ), Muñoz Maniega, S. (Susana), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (Bertram), Mwangi, B. (Benson), Nauck, M. (Matthias), Nho, K. (Kwangsik), Nichols, T.E. (Thomas), Nilsson, L.G., Nugent, A.C. (Allison), Nyberg, L. (Lisa), Olvera, R.L. (Rene), Oosterlaan, J. (Jaap), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Papalampropoulou-Tsiridou, M. (Melina), Papmeyer, M. (Martina), Paus, T. (Tomas), Pausova, Z. (Zdenka), Pearlson, G. (Godfrey), Penninx, B.W.J.H. (Brenda), Peterson, C.P. (Charles), Pfennig, A. (Andrea), Phillips, M. (Mary), Pike, G.B. (G Bruce), Poline, J.B. (Jean Baptiste), Potkin, S.G. (Steven), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Rasmussen, J. (Jerod), Rietschel, M. (Marcella), Rijpkema, M. (Mark), Risacher, S.L. (Shannon), Roffman, J.L. (Joshua), Roiz-Santiañez, R. (Roberto), Romanczuk-Seiferth, N. (Nina), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rujescu, D. (Dan), Ryten, M. (Mina), Sachdev, P.S. (Perminder), Salami, A. (Alireza), Satterthwaite, T.D. (Theodore), Savitz, J. (Jonathan), Saykin, A.J. (Andrew), Scanlon, C. (Cathy), Schmaal, L. (Lianne), Schnack, H. (Hugo), Schork, N.J. (Nicholas), Schulz, S.C. (S.Charles), Schür, R. (Remmelt), Seidman, L.J. (Larry), Shen, L. (Li), Shoemaker, L. (Lawrence), Simmons, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soares, J.C. (Jair), Sponheim, S.R. (Scott), Sprooten, R. (Roy), Starr, J.M. (John), Steen, V.M. (Vidar), Strakowski, S. (Stephen), Strike, L.T. (Lachlan), Sussmann, J. (Jessika), Sämann, P.G. (Philipp), Teumer, A. (Alexander), Toga, A.W. (Arthur), Tordesillas-Gutierrez, D. (Diana), Trabzuni, D. (Danyah), Trost, S. (Sarah), Turner, J. (Jessica), Heuvel, M. (Martijn) van den, Wee, N.J. (Nic) van der, Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Valdés Hernández, M.C. (Maria), Veltman, D.J. (Dick), Versace, A. (Amelia), Völzke, H. (Henry), Walker, R. (Robert), Walter, H.J. (Henrik), Wang, L. (Lei), Wardlaw, J.M. (J.), Weale, M.E. (Michael), Weiner, M.W. (Michael), Wen, W. (Wei), Westlye, L.T. (Lars), Whalley, H.C. (Heather), Whelan, C.D. (Christopher), White, T.J.H. (Tonya), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Zilles, D. (David), Zwiers, M.P. (Marcel), Thalamuthu, A. (Anbupalam), Almeida, J.R. (Jorge), Schofield, C.J. (Christopher), Freimer, N.B. (Nelson), Lawrence, N.S. (Natalia), and Drevets, D.A. (Douglas)
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
Published: 2014
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32. The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data

Author: Thompson, P., Stein, J., Medland, S., Hibar, D., Vasquez, A., Renteria, M., Toro, R., Jahanshad, N., Schumann, G., Franke, B., Wright, M., Martin, N., Agartz, I., Alda, M., Alhusaini, S., Almasy, L., Almeida, J., Alpert, K., Andreasen, N., Andreassen, O., Apostolova, L., Appel, K., Armstrong, N., Aribisala, B., Bastin, M., Bauer, M., Bearden, C., Bergmann, O., Binder, E., Blangero, J., Bockholt, H., Boen, E., Bois, C., Boomsma, D., Booth, T., Bowman, I., Bralten, J., Brouwer, R., Brunner, H., Brohawn, D., Buckner, R., Buitelaar, J., Bulayeva, K., Bustillo, J., Calhoun, V., Cannon, D., Cantor, R., Carless, M., Caseras, X., Cavalleri, G., Chakravarty, M., Chang, K., Ching, C., Christoforou, A., Cichon, S., Clark, V., Conrod, P., Coppola, G., Crespo-Facorro, B., Curran, J., Czisch, M., Deary, I., de Geus, E., den Braber, A., Delvecchio, G., Depondt, C., de Haan, L., de Zubicaray, G., Dima, D., Dimitrova, R., Djurovic, S., Dong, H., Donohoe, G., Duggirala, R., Dyer, T., Ehrlich, S., Ekman, C., Elvsashagen, T., Emsell, L., Erk, S., Espeseth, T., Fagerness, J., Fears, S., Fedko, I., Fernandez, G., Fisher, S., Foroud, T., Fox, P., Francks, C., Frangou, S., Frey, E., Frodl, T., Frouin, V., Garavan, H., Giddaluru, S., Glahn, D., Godlewska, B., Goldstein, R., Gollub, R., Grabe, H., Grimm, O., Gruber, O., Guadalupe, T., Gur, R., Goering, H., Hagenaars, S., Hajek, T., Hall, G., Hall, J., Hardy, J., Hartman, C., Hass, J., Hatton, S., Haukvik, U., Hegenscheid, K., Heinz, A., Hickie, I., Ho, B., Hoehn, D., Hoekstra, P., Hollinshead, M., Holmes, A., Homuth, G., Hoogman, M., Hong, L., Hosten, N., Hottenga, J., Pol, H., Hwang, K., Jack, C., Jenkinson, M., Johnston, C., Joensson, E., Kahn, R., Kasperaviciute, D., Kelly, S., Kim, S., Kochunov, P., Koenders, L., Kraemer, B., Kwok, J., Lagopoulos, J., Laje, G., Landen, M., Landman, B., Lauriello, J., Lawrie, S., Lee, P., Le Hellard, S., Lemaitre, H., Leonardo, C., Li, C., Liberg, B., Liewald, D., Liu, X., Lopez, L., Loth, E., Lourdusamy, A., Luciano, M., Macciardi, F., Machielsen, M., MacQueen, G., Malt, U., Mandl, R., Manoach, D., Martinot, J., Matarin, M., Mather, K., Mattheisen, M., Mattingsdal, M., Meyer-Lindenberg, A., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meisenzahl, E., Melle, I., Milaneschi, Y., Mohnke, S., Montgomery, G., Morris, D., Moses, Eric, Mueller, B., Munoz Maniega, S., Muehleisen, T., Mueller-Myhsok, B., Mwangi, B., Nauck, M., Nho, K., Nichols, T., Nilsson, L., Nugent, A., Nyberg, L., Olvera, R., Oosterlaan, J., Ophoff, R., Pandolfo, M., Papalampropoulou-Tsiridou, M., Papmeyer, M., Paus, T., Pausova, Z., Pearlson, G., Penninx, B., Peterson, C., Pfennig, A., Phillips, M., Pike, G., Poline, J., Potkin, S., Puetz, B., Ramasamy, A., Rasmussen, J., Rietschel, M., Rijpkema, M., Risacher, S., Roffman, J., Roiz-Santianez, R., Romanczuk-Seiferth, N., Rose, E., Royle, N., Rujescu, D., Ryten, M., Sachdev, P., Salami, A., Satterthwaite, T., Savitz, J., Saykin, A., Scanlon, C., Schmaal, L., Schnack, H., Schork, A., Schulz, S., Schuer, R., Seidman, L., Shen, L., Shoemaker, J., Simmons, A., Sisodiya, S., Smith, C., Smoller, J., Soares, J., Sponheim, S., Sprooten, E., Starr, J., Steen, V., Strakowski, S., Strike, L., Sussmann, J., Saemann, P., Teumer, A., Toga, A., Tordesillas-Gutierrez, D., Trabzuni, D., Trost, S., Turner, J., Van den Heuvel, M., van der Wee, N., van Eijk, K., van Erp, T., van Haren, N., van 't Ent, D., van Tol, M., Hernandez, M., Veltman, D., Versace, A., Voelzke, H., Walker, R., Walter, H., Wang, L., Wardlaw, J., Weale, M., Weiner, M., Wen, W., Westlye, L., Whalley, H., Whelan, C., White, T., Winkler, A., Wittfeld, K., Woldehawariat, G., Wolf, C., Zilles, D., Zwiers, M., Thalamuthu, A., Schofield, P., Freimer, N., Lawrence, N., Drevets, W., Thompson, P., Stein, J., Medland, S., Hibar, D., Vasquez, A., Renteria, M., Toro, R., Jahanshad, N., Schumann, G., Franke, B., Wright, M., Martin, N., Agartz, I., Alda, M., Alhusaini, S., Almasy, L., Almeida, J., Alpert, K., Andreasen, N., Andreassen, O., Apostolova, L., Appel, K., Armstrong, N., Aribisala, B., Bastin, M., Bauer, M., Bearden, C., Bergmann, O., Binder, E., Blangero, J., Bockholt, H., Boen, E., Bois, C., Boomsma, D., Booth, T., Bowman, I., Bralten, J., Brouwer, R., Brunner, H., Brohawn, D., Buckner, R., Buitelaar, J., Bulayeva, K., Bustillo, J., Calhoun, V., Cannon, D., Cantor, R., Carless, M., Caseras, X., Cavalleri, G., Chakravarty, M., Chang, K., Ching, C., Christoforou, A., Cichon, S., Clark, V., Conrod, P., Coppola, G., Crespo-Facorro, B., Curran, J., Czisch, M., Deary, I., de Geus, E., den Braber, A., Delvecchio, G., Depondt, C., de Haan, L., de Zubicaray, G., Dima, D., Dimitrova, R., Djurovic, S., Dong, H., Donohoe, G., Duggirala, R., Dyer, T., Ehrlich, S., Ekman, C., Elvsashagen, T., Emsell, L., Erk, S., Espeseth, T., Fagerness, J., Fears, S., Fedko, I., Fernandez, G., Fisher, S., Foroud, T., Fox, P., Francks, C., Frangou, S., Frey, E., Frodl, T., Frouin, V., Garavan, H., Giddaluru, S., Glahn, D., Godlewska, B., Goldstein, R., Gollub, R., Grabe, H., Grimm, O., Gruber, O., Guadalupe, T., Gur, R., Goering, H., Hagenaars, S., Hajek, T., Hall, G., Hall, J., Hardy, J., Hartman, C., Hass, J., Hatton, S., Haukvik, U., Hegenscheid, K., Heinz, A., Hickie, I., Ho, B., Hoehn, D., Hoekstra, P., Hollinshead, M., Holmes, A., Homuth, G., Hoogman, M., Hong, L., Hosten, N., Hottenga, J., Pol, H., Hwang, K., Jack, C., Jenkinson, M., Johnston, C., Joensson, E., Kahn, R., Kasperaviciute, D., Kelly, S., Kim, S., Kochunov, P., Koenders, L., Kraemer, B., Kwok, J., Lagopoulos, J., Laje, G., Landen, M., Landman, B., Lauriello, J., Lawrie, S., Lee, P., Le Hellard, S., Lemaitre, H., Leonardo, C., Li, C., Liberg, B., Liewald, D., Liu, X., Lopez, L., Loth, E., Lourdusamy, A., Luciano, M., Macciardi, F., Machielsen, M., MacQueen, G., Malt, U., Mandl, R., Manoach, D., Martinot, J., Matarin, M., Mather, K., Mattheisen, M., Mattingsdal, M., Meyer-Lindenberg, A., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meisenzahl, E., Melle, I., Milaneschi, Y., Mohnke, S., Montgomery, G., Morris, D., Moses, Eric, Mueller, B., Munoz Maniega, S., Muehleisen, T., Mueller-Myhsok, B., Mwangi, B., Nauck, M., Nho, K., Nichols, T., Nilsson, L., Nugent, A., Nyberg, L., Olvera, R., Oosterlaan, J., Ophoff, R., Pandolfo, M., Papalampropoulou-Tsiridou, M., Papmeyer, M., Paus, T., Pausova, Z., Pearlson, G., Penninx, B., Peterson, C., Pfennig, A., Phillips, M., Pike, G., Poline, J., Potkin, S., Puetz, B., Ramasamy, A., Rasmussen, J., Rietschel, M., Rijpkema, M., Risacher, S., Roffman, J., Roiz-Santianez, R., Romanczuk-Seiferth, N., Rose, E., Royle, N., Rujescu, D., Ryten, M., Sachdev, P., Salami, A., Satterthwaite, T., Savitz, J., Saykin, A., Scanlon, C., Schmaal, L., Schnack, H., Schork, A., Schulz, S., Schuer, R., Seidman, L., Shen, L., Shoemaker, J., Simmons, A., Sisodiya, S., Smith, C., Smoller, J., Soares, J., Sponheim, S., Sprooten, E., Starr, J., Steen, V., Strakowski, S., Strike, L., Sussmann, J., Saemann, P., Teumer, A., Toga, A., Tordesillas-Gutierrez, D., Trabzuni, D., Trost, S., Turner, J., Van den Heuvel, M., van der Wee, N., van Eijk, K., van Erp, T., van Haren, N., van 't Ent, D., van Tol, M., Hernandez, M., Veltman, D., Versace, A., Voelzke, H., Walker, R., Walter, H., Wang, L., Wardlaw, J., Weale, M., Weiner, M., Wen, W., Westlye, L., Whalley, H., Whelan, C., White, T., Winkler, A., Wittfeld, K., Woldehawariat, G., Wolf, C., Zilles, D., Zwiers, M., Thalamuthu, A., Schofield, P., Freimer, N., Lawrence, N., and Drevets, W.
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. Â© 2014 The Author(s).
Published: 2014

33. Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

Author: Kasperaviciute, D, Catarino, CB, Matarin, M, Leu, C, Novy, J, Tostevin, A, Leal, B, Hessel, EVS, Hallmann, K, Hildebrand, MS, Dahl, H-HM, Ryten, M, Trabzuni, D, Ramasamy, A, Alhusaini, S, Doherty, CP, Dorn, T, Hansen, J, Kraemer, G, Steinhoff, BJ, Zumsteg, D, Duncan, S, Kaelviaeinen, RK, Eriksson, KJ, Kantanen, A-M, Pandolfo, M, Gruber-Sedlmayr, U, Schlachter, K, Reinthaler, EM, Stogmann, E, Zimprich, F, Theatre, E, Smith, C, O'Brien, TJ, Tan, KM, Petrovski, S, Robbiano, A, Paravidino, R, Zara, F, Striano, P, Sperling, MR, Buono, RJ, Hakonarson, H, Chaves, J, Costa, PP, Silva, BM, da Silva, AM, de Graan, PNE, Koeleman, BPC, Becker, A, Schoch, S, von Lehe, M, Reif, PS, Rosenow, F, Becker, F, Weber, Y, Lerche, H, Roessler, K, Buchfelder, M, Hamer, HM, Kobow, K, Coras, R, Blumcke, I, Scheffer, IE, Berkovic, SF, Weale, ME, Delanty, N, Depondt, C, Cavalleri, GL, Kunz, WS, Sisodiya, SM, Kasperaviciute, D, Catarino, CB, Matarin, M, Leu, C, Novy, J, Tostevin, A, Leal, B, Hessel, EVS, Hallmann, K, Hildebrand, MS, Dahl, H-HM, Ryten, M, Trabzuni, D, Ramasamy, A, Alhusaini, S, Doherty, CP, Dorn, T, Hansen, J, Kraemer, G, Steinhoff, BJ, Zumsteg, D, Duncan, S, Kaelviaeinen, RK, Eriksson, KJ, Kantanen, A-M, Pandolfo, M, Gruber-Sedlmayr, U, Schlachter, K, Reinthaler, EM, Stogmann, E, Zimprich, F, Theatre, E, Smith, C, O'Brien, TJ, Tan, KM, Petrovski, S, Robbiano, A, Paravidino, R, Zara, F, Striano, P, Sperling, MR, Buono, RJ, Hakonarson, H, Chaves, J, Costa, PP, Silva, BM, da Silva, AM, de Graan, PNE, Koeleman, BPC, Becker, A, Schoch, S, von Lehe, M, Reif, PS, Rosenow, F, Becker, F, Weber, Y, Lerche, H, Roessler, K, Buchfelder, M, Hamer, HM, Kobow, K, Coras, R, Blumcke, I, Scheffer, IE, Berkovic, SF, Weale, ME, Delanty, N, Depondt, C, Cavalleri, GL, Kunz, WS, and Sisodiya, SM
Abstract: Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and
Published: 2013

34. Identification of common variants associated with human hippocampal and intracranial volumes.

Author: Stein, J.L., Medland, S.E., Arias Vasquez, A., Hibar, D.P., Senstad, R.E., Winkler, A.M., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, A.A., Cannon, D.M., Chakravarty, M.M., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., Holmes, A.J., Homuth, G., Hottenga, J.J., Langan, C., Lopez, L.M., Hansell, N.K., Hwang, K.S., Kim, S., Laje, G., Lee, P.H., Liu, X., Loth, E., Lourdusamy, A., Mattingsdal, M., Mohnke, S., Maniega, S.M., Nho, K., Nugent, A.C., O'Brien, C., Papmeyer, M., Putz, B., Ramasamy, A., Rasmussen, J., Rijpkema, M.J.P., Risacher, S.L., Roddey, J.C., Rose, E.J., Ryten, M., Shen, L., Sprooten, E., Strengman, E., Teumer, A., Trabzuni, D., Turner, J., Eijk, K. van, Erp, T.G. van, Tol, M.J. van, Wittfeld, K., Wolf, C. de, Woudstra, S., Aleman, A., Alhusaini, S., Almasy, L., Binder, E.B., Brohawn, D.G., Cantor, R.M., Carless, M.A., Corvin, A., Czisch, M., Curran, J.E., Davies, G., Almeida, M.A. de, Delanty, N., Depondt, C., Duggirala, R., Dyer, T.D., Erk, S., Fagerness, J., Fox, P.T., Freimer, N.B., Gill, M., Goring, H.H., Hagler, D.J., Hoehn, D., Holsboer, F., Hoogman, M., Hosten, N., Jahanshad, N., Johnson, M.P., Kasperaviciute, D., Kent Jr., J.W., Kochunov, P., Lancaster, J.L., Lawrie, S.M., Liewald, D.C., Mandl, R.C.W., Matarin, M., Mattheisen, M., Meisenzahl, E., Melle, I., Moses, E.K., Muhleisen, T.W., Nauck, M., Nothen, Markus, Olvera, R.L., Pandolfo, M., Pike, G.B., Puls, R., Reinvang, I., Renteria, M.E., Rietschel, M., Roffman, J.L., Royle, N.A., Rujescu, D., Savitz, J., Schnack, H.G., Schnell, K., Seiferth, N., Smith, C., Steen, V.M., Valdes Hernandez, M.C., Heuvel, M. van den, Wee, N.J.A. van der, Haren, N.E.M. van, Veltman, J.A., Volzke, H., Walker, R., Westlye, L.T., Whelan, C.D., Agartz, I., Boomsma, D.I., Cavalleri, G.L., Dale, A.M., Djurovic, S., Drevets, W.C., Hagoort, P., Hall, J., Heinz, A., Jack Jr., C.R., Foroud, T.M., Hellard, S. Le, Macciardi, F., Montgomery, G.W., Poline, J.B., Porteous, D.J., Sisodiya, S.M., Starr, J.M., Sussmann, J., Toga, A.W., Veltman, D.J., Walter, H., Weiner, M.W., Bis, J.C., Ikram, M.A., Smith, A.V., Gudnason, V., Tzourio, C., Vernooij, M.W., Launer, L.J., DeCarli, C., Seshadri, S., Andreassen, O.A., Apostolova, L.G., Bastin, M.E., Blangero, J., Brunner, H.G., Buckner, R.L., Cichon, S., Coppola, G., Zubicaray, G.I. de, Deary, I.J., Donohoe, G., Geus, E.J. de, Espeseth, T., Fernandez, G.S.E., Glahn, D.C., Grabe, H.J., Hardy, J., Hulshoff Pol, H.E., Jenkinson, M., Kahn, R.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Meyer-Lindenberg, A., Morris, D.W., Muller-Myhsok, B., Nichols, T.E., Ophoff, R.A., Paus, T., Pausova, Z., Penninx, B.W.J.H., Potkin, S.G., Samann, P.G., Saykin, A.J., Schumann, G., Smoller, J.W., Wardlaw, J.M., Weale, M.E., Martin, N.G., Franke, B., Wright, M.J., Thompson, P.M., Klaasen, A., et al., Stein, J.L., Medland, S.E., Arias Vasquez, A., Hibar, D.P., Senstad, R.E., Winkler, A.M., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, A.A., Cannon, D.M., Chakravarty, M.M., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., Holmes, A.J., Homuth, G., Hottenga, J.J., Langan, C., Lopez, L.M., Hansell, N.K., Hwang, K.S., Kim, S., Laje, G., Lee, P.H., Liu, X., Loth, E., Lourdusamy, A., Mattingsdal, M., Mohnke, S., Maniega, S.M., Nho, K., Nugent, A.C., O'Brien, C., Papmeyer, M., Putz, B., Ramasamy, A., Rasmussen, J., Rijpkema, M.J.P., Risacher, S.L., Roddey, J.C., Rose, E.J., Ryten, M., Shen, L., Sprooten, E., Strengman, E., Teumer, A., Trabzuni, D., Turner, J., Eijk, K. van, Erp, T.G. van, Tol, M.J. van, Wittfeld, K., Wolf, C. de, Woudstra, S., Aleman, A., Alhusaini, S., Almasy, L., Binder, E.B., Brohawn, D.G., Cantor, R.M., Carless, M.A., Corvin, A., Czisch, M., Curran, J.E., Davies, G., Almeida, M.A. de, Delanty, N., Depondt, C., Duggirala, R., Dyer, T.D., Erk, S., Fagerness, J., Fox, P.T., Freimer, N.B., Gill, M., Goring, H.H., Hagler, D.J., Hoehn, D., Holsboer, F., Hoogman, M., Hosten, N., Jahanshad, N., Johnson, M.P., Kasperaviciute, D., Kent Jr., J.W., Kochunov, P., Lancaster, J.L., Lawrie, S.M., Liewald, D.C., Mandl, R.C.W., Matarin, M., Mattheisen, M., Meisenzahl, E., Melle, I., Moses, E.K., Muhleisen, T.W., Nauck, M., Nothen, Markus, Olvera, R.L., Pandolfo, M., Pike, G.B., Puls, R., Reinvang, I., Renteria, M.E., Rietschel, M., Roffman, J.L., Royle, N.A., Rujescu, D., Savitz, J., Schnack, H.G., Schnell, K., Seiferth, N., Smith, C., Steen, V.M., Valdes Hernandez, M.C., Heuvel, M. van den, Wee, N.J.A. van der, Haren, N.E.M. van, Veltman, J.A., Volzke, H., Walker, R., Westlye, L.T., Whelan, C.D., Agartz, I., Boomsma, D.I., Cavalleri, G.L., Dale, A.M., Djurovic, S., Drevets, W.C., Hagoort, P., Hall, J., Heinz, A., Jack Jr., C.R., Foroud, T.M., Hellard, S. Le, Macciardi, F., Montgomery, G.W., Poline, J.B., Porteous, D.J., Sisodiya, S.M., Starr, J.M., Sussmann, J., Toga, A.W., Veltman, D.J., Walter, H., Weiner, M.W., Bis, J.C., Ikram, M.A., Smith, A.V., Gudnason, V., Tzourio, C., Vernooij, M.W., Launer, L.J., DeCarli, C., Seshadri, S., Andreassen, O.A., Apostolova, L.G., Bastin, M.E., Blangero, J., Brunner, H.G., Buckner, R.L., Cichon, S., Coppola, G., Zubicaray, G.I. de, Deary, I.J., Donohoe, G., Geus, E.J. de, Espeseth, T., Fernandez, G.S.E., Glahn, D.C., Grabe, H.J., Hardy, J., Hulshoff Pol, H.E., Jenkinson, M., Kahn, R.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Meyer-Lindenberg, A., Morris, D.W., Muller-Myhsok, B., Nichols, T.E., Ophoff, R.A., Paus, T., Pausova, Z., Penninx, B.W.J.H., Potkin, S.G., Samann, P.G., Saykin, A.J., Schumann, G., Smoller, J.W., Wardlaw, J.M., Weale, M.E., Martin, N.G., Franke, B., Wright, M.J., Thompson, P.M., Klaasen, A., and et al.
Abstract: 01 mei 2012, Contains fulltext : 108202.pdf (publisher's version ) (Closed access), Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)).
Published: 2012

35. Identification of common variants associated with human hippocampal and intracranial volumes

Author: Stein, J., Medland, S., Vasquez, A., Hibar, D., Senstad, R., Winkler, A., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, A., Cannon, D., Chakravarty, M., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., Holmes, A., Homuth, G., Hottenga, J., Langan, C., Lopez, L., Hansell, N., Hwang, K., Kim, S., Laje, G., Lee, P., Liu, X., Loth, E., Lourdusamy, A., Mattingsdal, M., Mohnke, S., Maniega, S., Nho, K., Nugent, A., O'Brien, C., Papmeyer, M., Putz, B., Ramasamy, A., Rasmussen, J., Rijpkema, M., Risacher, S., Roddey, J., Rose, E., Ryten, M., Shen, L., Sprooten, E., Strengman, E., Teumer, A., Trabzuni, D., Turner, J., van Eijk, K., van Erp, T., van Tol, M., Wittfeld, K., Wolf, C., Woudstra, S., Aleman, A., Alhusaini, S., Almasy, L., Binder, E., Brohawn, D., Cantor, R., Carless, M., Corvin, A., Czisch, M., Curran, J., Davies, G., de Almeida, M., Delanty, N., Depondt, C., Duggirala, R., Dyer, T., Erk, S., Fagerness, J., Fox, P., Freimer, N., Gill, M., Goering, H., Hagler, D., Hoehn, D., Holsboer, F., Hoogman, M., Hosten, N., Jahanshad, N., Johnson, M., Kasperaviciute, D., Kent, J., Kochunov, P., Lancaster, J., Lawrie, S., Liewald, D., Mandl, R., Matarin, M., Mattheisen, M., Meisenzahl, E., Melle, I., Moses, Eric, Muehleisen, T., Nauck, M., Noethen, M., Olvera, R., Pandolfo, M., Pike, G., Puls, R., Reinvang, I., Renteria, M., Rietschel, M., Roffman, J., Royle, N., Rujescu, D., Savitz, J., Schnack, H., Schnell, K., Seiferth, N., Smith, C., Steen, V., Hernandez, M., Van den Heuvel, M., van der Wee, N., Van Haren, N., Veltman, J., Voelzke, H., Walker, R., Westlye, L., Whelan, C., Agartz, I., Boomsma, D., Cavalleri, G., Dale, A., Djurovic, S., Drevets, W., Hagoort, P., Hall, J., Heinz, A., Jack, C., Foroud, T., Le Hellard, S., Macciardi, F., Montgomery, G., Poline, J., Porteous, D., Sisodiya, S., Starr, J., Sussmann, J., Toga, A., Veltman, D., Walter, H., Weiner, M., Bis, J., Ikram, M., Smith, A., Gudnason, V., Tzourio, C., Vernooij, M., Launer, L., DeCarli, C., Seshadri, S., Andreassen, O., Apostolova, L., Bastin, M., Blangero, J., Brunner, H., Buckner, R., Cichon, S., Coppola, G., de Zubicaray, G., Deary, I., Donohoe, G., de Geus, E., Espeseth, T., Fernandez, G., Glahn, D., Grabe, H., Hardy, J., Pol, H., Jenkinson, M., Kahn, R., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meyer-Lindenberg, A., Morris, D., Mueller-Myhsok, B., Nichols, T., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Potkin, S., Saemann, P., Saykin, A., Schumann, G., Smoller, J., Wardlaw, J., Weale, M., Martin, N., Franke, B., Wright, M., Thompson, P., Stein, J., Medland, S., Vasquez, A., Hibar, D., Senstad, R., Winkler, A., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, A., Cannon, D., Chakravarty, M., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., Holmes, A., Homuth, G., Hottenga, J., Langan, C., Lopez, L., Hansell, N., Hwang, K., Kim, S., Laje, G., Lee, P., Liu, X., Loth, E., Lourdusamy, A., Mattingsdal, M., Mohnke, S., Maniega, S., Nho, K., Nugent, A., O'Brien, C., Papmeyer, M., Putz, B., Ramasamy, A., Rasmussen, J., Rijpkema, M., Risacher, S., Roddey, J., Rose, E., Ryten, M., Shen, L., Sprooten, E., Strengman, E., Teumer, A., Trabzuni, D., Turner, J., van Eijk, K., van Erp, T., van Tol, M., Wittfeld, K., Wolf, C., Woudstra, S., Aleman, A., Alhusaini, S., Almasy, L., Binder, E., Brohawn, D., Cantor, R., Carless, M., Corvin, A., Czisch, M., Curran, J., Davies, G., de Almeida, M., Delanty, N., Depondt, C., Duggirala, R., Dyer, T., Erk, S., Fagerness, J., Fox, P., Freimer, N., Gill, M., Goering, H., Hagler, D., Hoehn, D., Holsboer, F., Hoogman, M., Hosten, N., Jahanshad, N., Johnson, M., Kasperaviciute, D., Kent, J., Kochunov, P., Lancaster, J., Lawrie, S., Liewald, D., Mandl, R., Matarin, M., Mattheisen, M., Meisenzahl, E., Melle, I., Moses, Eric, Muehleisen, T., Nauck, M., Noethen, M., Olvera, R., Pandolfo, M., Pike, G., Puls, R., Reinvang, I., Renteria, M., Rietschel, M., Roffman, J., Royle, N., Rujescu, D., Savitz, J., Schnack, H., Schnell, K., Seiferth, N., Smith, C., Steen, V., Hernandez, M., Van den Heuvel, M., van der Wee, N., Van Haren, N., Veltman, J., Voelzke, H., Walker, R., Westlye, L., Whelan, C., Agartz, I., Boomsma, D., Cavalleri, G., Dale, A., Djurovic, S., Drevets, W., Hagoort, P., Hall, J., Heinz, A., Jack, C., Foroud, T., Le Hellard, S., Macciardi, F., Montgomery, G., Poline, J., Porteous, D., Sisodiya, S., Starr, J., Sussmann, J., Toga, A., Veltman, D., Walter, H., Weiner, M., Bis, J., Ikram, M., Smith, A., Gudnason, V., Tzourio, C., Vernooij, M., Launer, L., DeCarli, C., Seshadri, S., Andreassen, O., Apostolova, L., Bastin, M., Blangero, J., Brunner, H., Buckner, R., Cichon, S., Coppola, G., de Zubicaray, G., Deary, I., Donohoe, G., de Geus, E., Espeseth, T., Fernandez, G., Glahn, D., Grabe, H., Hardy, J., Pol, H., Jenkinson, M., Kahn, R., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meyer-Lindenberg, A., Morris, D., Mueller-Myhsok, B., Nichols, T., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Potkin, S., Saemann, P., Saykin, A., Schumann, G., Smoller, J., Wardlaw, J., Weale, M., Martin, N., Franke, B., Wright, M., and Thompson, P.
Abstract: Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 Ã— 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 Ã— 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 Ã— 10 -7). Â© 2012 Nature America, Inc. All rights reserved.
Published: 2012

36. Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study

Author: Kasperaviciūte, D, Catarino, C B, Heinzen, E L, Depondt, C, Cavalleri, G L, Caboclo, L O, Tate, S K, Jamnadas-Khoda, J, Chinthapalli, K, Clayton, L M S, Shianna, K V, Radtke, R A, Mikati, M A, Gallentine, W B, Husain, A M, Alhusaini, S, Leppert, D, Middleton, L T, Gibson, R A, Johnson, M R, Matthews, P M, Hosford, D, Heuser, K, Amos, L, Ortega, M, Zumsteg, D, Wieser, H G, Steinhoff, B J, Krämer, G, Hansen, J, Dorn, T, Kantanen, A M, Gjerstad, L, Peuralinna, T, Hernandez, D G, Eriksson, K J, Kälviäinen, R K, Doherty, C P, Wood, N W, Pandolfo, M, Duncan, J S, Sander, J W, Delanty, N, Goldstein, D B, Sisodiya, S M, Kasperaviciūte, D, Catarino, C B, Heinzen, E L, Depondt, C, Cavalleri, G L, Caboclo, L O, Tate, S K, Jamnadas-Khoda, J, Chinthapalli, K, Clayton, L M S, Shianna, K V, Radtke, R A, Mikati, M A, Gallentine, W B, Husain, A M, Alhusaini, S, Leppert, D, Middleton, L T, Gibson, R A, Johnson, M R, Matthews, P M, Hosford, D, Heuser, K, Amos, L, Ortega, M, Zumsteg, D, Wieser, H G, Steinhoff, B J, Krämer, G, Hansen, J, Dorn, T, Kantanen, A M, Gjerstad, L, Peuralinna, T, Hernandez, D G, Eriksson, K J, Kälviäinen, R K, Doherty, C P, Wood, N W, Pandolfo, M, Duncan, J S, Sander, J W, Delanty, N, Goldstein, D B, and Sisodiya, S M
Abstract: Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio<1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.
Published: 2010

37. The role of endoplasmic reticulum in human adipose tissue

Author: Alhusaini, S. (Saif)
Subjects: QP
Abstract: Adipose tissue plays a central role in the regulation of metabolic homeostasis. In\ud obesity adipocytes are challenged by many insults: surplus energy, inflammation,\ud insulin resistance and considerable endoplasmic reticulum (ER) stress. ER stress has\ud been casually linked to increased inflammation and insulin resistance. Also, obesity\ud linked type 2 diabetes is associated with hyperglycaemia, lipotoxicity and\ud endotoxemia. Therefore, the aims of this thesis briefly were to 1) characterise human\ud pre-adipocytes during differentiation, as a suitable primary cellular model to examine\ud intracellular pathways, 2) investigate the role of glucose and fatty acids on ER stress\ud pathway; as these primary insults are considered to have clear impact on\ud inflammation, insulin resistance (IR) status and diabetes pathogenesis 3) to examine\ud the role of lipopolysaccharide (LPS), a gut derived bacterial fragment, on ER stress;\ud as LPS is now considered a systemic circulating factor raised in conditions of IR, 4)\ud the role of salicylate, known to have anti-inflammatory properties which may negate\ud or at least attenuate the effects of ER stress.\ud Components of the ER stress pathways were studied in human abdominal\ud subcutaneous (AbSc) adipose tissue (AT) from obese and lean subjects. Following\ud characterisation, culture and differentiation of primary human pre-adipocytes, these\ud adipocytes were treated with lipopolysaccharide (LPS), high glucose (HG),\ud tunicamycin (Tun) and saturated fatty acids (SFA) either alone or in combination with\ud sodium salicylate (Sal). Quantitative RT-PCR, western blotting, adipokine analysis\ud were used to assess expression levels.\ud Markers of ER stress were significantly increased in AbSc AT from subjects with\ud obesity (P

38. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author: Pm, Thompson, Jl, Stein, Se, Medland, Dp, Hibar, Aa, Vasquez, Me, Renteria, Toro R, Jahanshad N, Schumann G, Franke B, Mj, Wright, Ng, Martin, Agartz I, Alda M, Alhusaini S, Almasy L, Almeida J, Alpert K, Nc, Andreasen, Oa, Andreassen, Lg, Apostolova, Appel K, Nj, Armstrong, Aribisala B, Me, Bastin, Bauer M, Ce, Bearden, Bergmann O, Eb, Binder, Blangero J, Hj, Bockholt, Bøen E, Bois C, Di, Boomsma, Booth T, Ij, Bowman, Bralten J, Rm, Brouwer, Hg, Brunner, Dg, Brohawn, Rl, Buckner, Buitelaar J, Bulayeva K, Jr, Bustillo, Vd, Calhoun, Dm, Cannon, Rm, Cantor, Ma, Carless, Caseras X, Gl, Cavalleri, Mm, Chakravarty, Kd, Chang, Cr, Ching, Christoforou A, Cichon S, Vp, Clark, Conrod P, Coppola G, Crespo-Facorro B, Je, Curran, Czisch M, Ij, Deary, Ej, Geus, den Braber A, Delvecchio G, Depondt C, de Haan L, Gi, Zubicaray, Dima D, Dimitrova R, Djurovic S, Dong H, Donohoe G, Duggirala R, Td, Dyer, Ehrlich S, Cj, Ekman, Elvsåshagen T, Emsell L, Erk S, Espeseth T, Fagerness J, Fears S, Fedko I, Fernández G, Se, Fisher, Foroud T, Pt, Fox, Francks C, Frangou S, Em, Frey, Frodl T, Frouin V, Garavan H, Giddaluru S, Dc, Glahn, Godlewska B, Rz, Goldstein, Rl, Gollub, Hj, Grabe, Grimm O, Gruber O, Guadalupe T, Re, Gur, Rc, Gur, Hh, Göring, Hagenaars S, Hajek T, Gb, Hall, Hall J, Hardy J, Ca, Hartman, Hass J, Sn, Hatton, Uk, Haukvik, Hegenscheid K, Heinz A, Ib, Hickie, Bc, Ho, Hoehn D, Pj, Hoekstra, Hollinshead M, Aj, Holmes, Homuth G, Martine Hoogman, Le, Hong, Hosten N, Jj, Hottenga, He, Hulshoff Pol, Ks, Hwang, Cr, Jack Jr, Jenkinson M, Johnston C, Eg, Jönsson, Rs, Kahn, Kasperaviciute D, Kelly S, Kim S, Kochunov P, Koenders L, Krämer B, Jb, Kwok, Lagopoulos J, Laje G, Landen M, Ba, Landman, Lauriello J, Sm, Lawrie, Ph, Lee, Le Hellard S, Lemaître H, Cd, Leonardo, Cs, Li, Liberg B, Dc, Liewald, Liu X, Lm, Lopez, Loth E, Lourdusamy A, Luciano M, Macciardi F, Mw, Machielsen, Gm, Macqueen, Uf, Malt, Mandl R, Ds, Manoach, Jl, Martinot, Matarin M, Ka, Mather, Mattheisen M, Mattingsdal M, Meyer-Lindenberg A, McDonald C, Am, Mcintosh, Fj, Mcmahon, Kl, Mcmahon, Meisenzahl E, Melle I, Milaneschi Y, Mohnke S, Gw, Montgomery, Dw, Morris, Ek, Moses, Ba, Mueller, Muñoz Maniega S, Tw, Mühleisen, Müller-Myhsok B, Mwangi B, Nauck M, Nho K, Te, Nichols, Lg, Nilsson, Ac, Nugent, Nyberg L, Rl, Olvera, Oosterlaan J, Ra, Ophoff, Pandolfo M, Papalampropoulou-Tsiridou M, Papmeyer M, Paus T, Pausova Z, Gd, Pearlson, Bw, Penninx, Cp, Peterson, Pfennig A, Phillips M, Gb, Pike, Jb, Poline, Sg, Potkin, Pütz B, Ramasamy A, Rasmussen J, Rietschel M, Rijpkema M, Sl, Risacher, Jl, Roffman, Roiz-Santiañez R, Romanczuk-Seiferth N, Ej, Rose, Na, Royle, Rujescu D, Ryten M, Ps, Sachdev, Salami A, Td, Satterthwaite, Savitz J, Aj, Saykin, Scanlon C, Schmaal L, Hg, Schnack, Aj, Schork, Sc, Schulz, Schür R, Seidman L, Shen L, Jm, Shoemaker, Simmons A, Sm, Sisodiya, Smith C, Jw, Smoller, Jc, Soares, Sr, Sponheim, Sprooten E, Jm, Starr, Vm, Steen, Strakowski S, Strike L, Sussmann J, Pg, Sämann, Teumer A, Aw, Toga, Tordesillas-Gutierrez D, Trabzuni D, Trost S, Turner J, Van den Heuvel M, Nj, Wee, van Eijk K, Tg, Erp, Ne, Haren, van 't Ent D, Mj, Tol, Mc, Valdés Hernández, Dj, Veltman, Versace A, Völzke H, Walker R, Walter H, Wang L, Jm, Wardlaw, Me, Weale, Mw, Weiner, Wen W, Lt, Westlye, Hc, Whalley, Cd, Whelan, White T, Am, Winkler, Wittfeld K, Woldehawariat G, Wolf C, Zilles D, Mp, Zwiers, Thalamuthu A, Pr, Schofield, Nb, Freimer, Ns, Lawrence, Drevets W, The Alzheimer’s Disease Neuroimaging Initiative, Epigen Consortium, Laboratory of Neuro Imaging [Los Angeles] (LONI), University of California [Los Angeles] (UCLA), University of California-University of California, David Geffen School of Medicine [Los Angeles], Medstar Research Institute, Keck School of Medicine [Los Angeles], University of Southern California (USC), Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Department of Psychiatry, Donders Centre for Neuroscience, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Genetic Epidemiology Lab [Brisbane], Queensland Institute of Medical Research, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Dalhousie University [Halifax], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Department of Genetics, Southwest Foundation for Biomedical Research, Departamento de Matemática Pura, Faculdade de Ciências (UNIVERSIDADE DO PORTO), Universidade do Porto = University of Porto, Department of Psychiatry and Psychotherapy, University of Edinburgh, Center for Sepsis Control & Care, Jena University Hospital, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Texas Biomedical Research Institute [San Antonio, TX], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Radboud University Medical Center [Nijmegen], Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Department of Genomics, Douglas Mental Health University Institute, McGill University = Université McGill [Montréal, Canada], sans affiliation, Università degli Studi di Salermo, Università degli Studi di Salerno (UNISA), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), School of Psychology, University of Queensland, University of Queensland [Brisbane], Department of Hematology, 'Ion Chiricuta' Cancer Institute, University of Oslo (UiO), The University of Texas Health Science Center at Houston (UTHealth), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Department of Psychiatry, Division of Medical Psychology, Champalimaud Neuroscience Programme, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Division of Hemato-Oncology, Saint Anna Children's Hospital [Vienne] = St Anna Kinderspital (St. Anna Children's Hospital), Psychiatry and Psychotherapy, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Vermont [Burlington], Haukeland University Hospital, University of Bergen (UiB), Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Laboratory of Molecular Neuropsychiatry, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg], International Max Planck Research School for Language Sciences (IMPRS ), Lancaster University, Georgia Institute of Technology [Atlanta], Greifswald University Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Clinical Research Unit, Brain & Mind Research Institute-The University of Sydney, Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, University Medical Center Groningen [Groningen] (UMCG), Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Mental Health Sciences Unit, University College of London [London] (UCL), University Medical Center [Utrecht], Department of Radiology [Rochester], Mayo Clinic [Rochester], Department of Clinical Neurology [Oxford], University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], Centre for the Cellular Basis of Behavior, Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Medicine, Imperial College London, MetaCase [Jyväskylä], Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, University of Maryland System, Sahlgrenska Academy at University of Gothenburg [Göteborg], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Université de Cergy Pontoise (UCP), Université Paris-Seine, National Institutes of Health [Bethesda] (NIH), Department of Forensic and Neurodevelopmental Sciences, University of California [Irvine] (UCI), University of California, Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], VU University Medical Center [Amsterdam], Metacohorts Consortium, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Indiana Alzheimer Disease Center, Department of Statistics [Warwick], University of Warwick [Coventry], Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, University of Pennsylvania [Philadelphia], Department of Cognitive Sciences [San Diego], University of California [San Diego] (UC San Diego), Indiana University System, Natbrainlab, Department of Forensic and Neurodevelopmental Sciences, Institute of psychiatry-King‘s College London, Institute of Neurology [London], Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], King Faisal Specialist Hospital and Research Centre, Georgia State University, University System of Georgia (USG), Department of Psychiatry and Human Behavior [Irvine], Leiden University Medical Center (LUMC), Institute for Community Medicine, School of Music and Music Education (UNSW), Science & Technology Information Institute, Shandong Academy of Agricultural Science, University of California [San Francisco] (UCSF), Department of Physics [Hong Kong University of Science and Technology], Hong Kong University of Science and Technology (HKUST), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Research Laboratory for Archaeology & the History of Art, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dundee Technopole, CXR Biosciences Ltd, Georg-August-University [Göttingen], Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Prince of Wales Medical Research Institute, Center for Neurobehavioral Genetics, Wales Institute of Cognitive Neuroscience, Cardiff University, Complutense University of Madrid (UCM), Universidade do Porto [Porto], Texas Biomedical Research Institute [San Antonio, Texas], Karakter Child and Adolescent Psychiatry University Centre, McGill University, Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), St. Anna Children's Hospital, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Bergen (UIB), Yale University School of Medicine, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), McGill University-McGill University, Technische Universität Dresden (TUD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Inria Saclay - Ile de France, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Physics [Kowloon], University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet, Karolinska University Hospital [Stockholm], Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University [Chicago, Ill. USA], Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Ernst-Moritz-Arndt-Universität Greifswald, School of Mathematics and Statistics, Brain Research Imaging Centre, Imaging Sciences, University Hospital Carl Gustav Carus [Dresden, Germany], Semel Institute for Neuroscience and Human Behavior [Los Angeles, Ca], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Royal Hospital for Sick Children [Edinburgh], Department of General Practice/EMGO Institute, Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh-Medical Research Council (MRC), Radboud University [Nijmegen], Brain Centre Rudolf Magnus [Utrecht], Department of Human Genetics [Nijmegen], Psychiatric and Neurodevelopmental Genetics Unit, Harvard University, Russian Academy of Sciences [Moscow] (RAS), The University of New Mexico [Albuquerque], The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), National University of Ireland [Galway] (NUI Galway), University of California (UC), Institute of Psychological Medicine and Clinical Neurosciences, Centre for Addiction and Mental Health [Toronto] (CAMH), Institute of Biomaterials and Biomedical Engineering [Toronto, ON, Canada] (IBBME), University of Toronto, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Universität Bonn = University of Bonn, Jülich Research Centre, University of Basel (Unibas), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Fundación Marqués de Valdecilla-Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Centre for Cognitive Ageing and Cognitive Epidemiology, Trinity College Dublin, Department of Psychiatry Massachusetts General Hospital (MGH), South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, University Hospital Regensburg, Hartford Hospital, University of Oxford, HELIOS Klinikum Stralsund Hanseatic, University of Heidelberg, Medical Faculty, Georg-August-University = Georg-August-Universität Göttingen, University of Pennsylvania, McMaster University [Hamilton, Ontario], UCL, Institute of Neurology [London], Brain and Mind Research Institute, University of Technology Sydney (UTS), Diakonhjemmet Hospital, University of Maryland School of Medicine, Oakland University, University of Rochester School of Medicine, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), South London and Maudsley NHS Foundation Trust, Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Maryland [Baltimore], Neuroscience Research Australia (NeuRA), University of Gothenburg (GU), Karolinska Institutet [Stockholm], Vanderbilt University [Nashville], University of Missouri [Columbia] (Mizzou), University of Missouri System, Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neuroscience, Yale University School of Medicine, Columbia University Medical Center (CUMC), Columbia University [New York], University of Nottingham, UK (UON), University of California [Irvine] (UC Irvine), Università degli Studi di Milano = University of Milan (UNIMI), Hotchkiss Brain Institute, University of Calgary, Oslo and Akershus University College of Applied Sciences [Oslo] (HiOA), Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Aarhus University [Aarhus], Sorlandet Hospital HF, University Hospital Mannheim | Universitätsmedizin Mannheim, Centre for Advanced Imaging [Brisbane] (CAI), Ludwig Maximilian University [Munich] (LMU), Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, The University of Western Australia (UWA), University of Minnesota [Morris], University of Minnesota System, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), The University of Texas Medical School at Houston, Indiana State University, Stockholm Brain Institute [Stockholm, Sweden], Stockholm University, Umeå University, University of Texas Health Science Center, Department of Clinical Neuropsychology, University of Amsterdam [Amsterdam] (UvA), Rotman Research Institute at the Baycrest Centre (RRI), The Hospital for sick children [Toronto] (SickKids), University of Pittsburgh (PITT), University of California [Berkeley] (UC Berkeley), King's College, Reta Lila Weston Institute, UCL Institute of Neurology, Department of Molecular Neuroscience, University College of London [London] (UCL)-Institute of Neurology, University of Cantabria, Santander, Research Triangle Institute International (RTI International), Martin-Luther-Universität Halle Wittenberg (MLU), Prince of Wales Hospital, Karolinska Institute, Laureate institute for brain research, Tulsa, University of Tulsa, Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), University of Minnesota Medical School, Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Maudsley NHS Foundation Trust and Institute of Psychiatry, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Edinburgh Dementia Prevention & Centre for Clinical Brain Sciences, Center for Human Genetic Research, VA NY Harbor Health Care System, Alzheimer Scotland Dementia Research Centre, Department of Psychiatry and Behavioral Neuroscience [UC, Cincinnati], University of Cincinnati (UC), University of Cincinnati College of Medicine, Marqués de Valdecilla University Hospital [Santander], King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Psychiatry and Leiden Institute for Brain and Cognition, Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), The Centre for Regenerative Medicine, Berlin School of Mind and Brain [Berlin], Humboldt University Of Berlin, University of California [San Francisco] (UC San Francisco), School of Chemistry, University of Edinburgh, Department of Public Health, Erasmus University Medical Centre, Rotterdam, Erasmus University Medical Centre, Rotterdam, Department of Psychiatry and Biobehavioral Sciences, University of Exeter, Janssen Research & Development, A complete listing of ADNI investigators is available at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf The work reviewed here was funded by a large number of federal and private agencies worldwide, listed in Stein et al. (2012), the funding for listed consortia is also itemized in Stein et al. (2012)., Medical Oncology, Epidemiology, Clinical Chemistry, Cardiology, Neurosciences, Child and Adolescent Psychiatry / Psychology, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Universidade do Porto, FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Université de Lorraine (UL)-Université de Strasbourg (UNISTRA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Service NEUROSPIN (NEUROSPIN), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Smoller, Jordan, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANS - Amsterdam Neuroscience, Adult Psychiatry, Other departments, University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: endocrine system, Multi-site, Cognitive Neuroscience, [SDV]Life Sciences [q-bio], body-mass index, Clinical Neurology, multivariate parallel ica, Neuroimaging, methods [Genome-Wide Association Study], human brain structure, methods [Brain Mapping], Behavioral Neuroscience, Cellular and Molecular Neuroscience, ddc:150, Meta-Analysis as Topic, cortical surface-area, Genetics, voxel-based morphometry, GWAS, Humans, Cooperative Behavior, disease risk variant, Brain Mapping, MRI, Consortium, Meta-analysis, white-matter microstructure, SI: Genetic Neuroimaging in Aging and Age-Related Diseases, Psychiatry and Mental health, Neurology, Radiology Nuclear Medicine and imaging, quantitative trait loci, RC0321, genome-wide association, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], tensor-based morphometry, methods [Neuroimaging], Genome-Wide Association Study
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA’s first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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39. Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study

Author: Kasperaviciūte, D, Catarino, C B, Heinzen, E L, Depondt, C, Cavalleri, G L, Caboclo, L O, Tate, S K, Jamnadas-Khoda, J, Chinthapalli, K, Clayton, L M S, Shianna, K V, Radtke, R A, Mikati, M A, Gallentine, W B, Husain, A M, Alhusaini, S, Leppert, D, Middleton, L T, Gibson, R A, Johnson, M R, Matthews, P M, Hosford, D, Heuser, K, Amos, L, Ortega, M, Zumsteg, D, Wieser, H G, Steinhoff, B J, Krämer, G, Hansen, J, Dorn, T, Kantanen, A M, Gjerstad, L, Peuralinna, T, Hernandez, D G, Eriksson, K J, Kälviäinen, R K, Doherty, C P, Wood, N W, Pandolfo, M, Duncan, J S, Sander, J W, Delanty, N, Goldstein, D B, and Sisodiya, S M
Subjects: 3. Good health

40. MEK Pathway Inhibitor-Mediated Response in BRAF V600-Mutant Melanoma with Brain Parenchymal and Leptomeningeal Metastases.

Author: Alhusaini S, Naya L, Reddy SA, and Patel CB
Published: 2024
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41. Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.

Author: García-Marín LM, Campos AI, Diaz-Torres S, Rabinowitz JA, Ceja Z, Mitchell BL, Grasby KL, Thorp JG, Agartz I, Alhusaini S, Ames D, Amouyel P, Andreassen OA, Arfanakis K, Arias-Vasquez A, Armstrong NJ, Athanasiu L, Bastin ME, Beiser AS, Bennett DA, Bis JC, Boks MPM, Boomsma DI, Brodaty H, Brouwer RM, Buitelaar JK, Burkhardt R, Cahn W, Calhoun VD, Carmichael OT, Chakravarty M, Chen Q, Ching CRK, Cichon S, Crespo-Facorro B, Crivello F, Dale AM, Smith GD, de Geus EJC, De Jager PL, de Zubicaray GI, Debette S, DeCarli C, Depondt C, Desrivières S, Djurovic S, Ehrlich S, Erk S, Espeseth T, Fernández G, Filippi I, Fisher SE, Fleischman DA, Fletcher E, Fornage M, Forstner AJ, Francks C, Franke B, Ge T, Goldman AL, Grabe HJ, Green RC, Grimm O, Groenewold NA, Gruber O, Gudnason V, Håberg AK, Haukvik UK, Heinz A, Hibar DP, Hilal S, Himali JJ, Ho BC, Hoehn DF, Hoekstra PJ, Hofer E, Hoffmann W, Holmes AJ, Homuth G, Hosten N, Ikram MK, Ipser JC, Jack CR Jr, Jahanshad N, Jönsson EG, Kahn RS, Kanai R, Klein M, Knol MJ, Launer LJ, Lawrie SM, Hellard SL, Lee PH, Lemaître H, Li S, Liewald DCM, Lin H, Longstreth WT Jr, Lopez OL, Luciano M, Maillard P, Marquand AF, Martin NG, Martinot JL, Mather KA, Mattay VS, McMahon KL, Mecocci P, Melle I, Meyer-Lindenberg A, Mirza-Schreiber N, Milaneschi Y, Mosley TH, Mühleisen TW, Müller-Myhsok B, Maniega SM, Nauck M, Nho K, Niessen WJ, Nöthen MM, Nyquist PA, Oosterlaan J, Pandolfo M, Paus T, Pausova Z, Penninx BWJH, Pike GB, Psaty BM, Pütz B, Reppermund S, Rietschel MD, Risacher SL, Romanczuk-Seiferth N, Romero-Garcia R, Roshchupkin GV, Rotter JI, Sachdev PS, Sämann PG, Saremi A, Sargurupremraj M, Saykin AJ, Schmaal L, Schmidt H, Schmidt R, Schofield PR, Scholz M, Schumann G, Schwarz E, Shen L, Shin J, Sisodiya SM, Smith AV, Smoller JW, Soininen HS, Steen VM, Stein DJ, Stein JL, Thomopoulos SI, Toga AW, Tordesillas-Gutiérrez D, Trollor JN, Valdes-Hernandez MC, van T Ent D, van Bokhoven H, van der Meer D, van der Wee NJA, Vázquez-Bourgon J, Veltman DJ, Vernooij MW, Villringer A, Vinke LN, Völzke H, Walter H, Wardlaw JM, Weinberger DR, Weiner MW, Wen W, Westlye LT, Westman E, White T, Witte AV, Wolf C, Yang J, Zwiers MP, Ikram MA, Seshadri S, Thompson PM, Satizabal CL, Medland SE, and Rentería ME
Subjects: Humans, Female, Male, Organ Size genetics, Attention Deficit Disorder with Hyperactivity genetics, Attention Deficit Disorder with Hyperactivity pathology, Parkinson Disease genetics, Parkinson Disease pathology, Polymorphism, Single Nucleotide, Genomics methods, Adult, Genetic Predisposition to Disease, Middle Aged, White People genetics, Genome-Wide Association Study, Multifactorial Inheritance genetics, Brain pathology
Abstract: Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2024
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42. Experience from a Fast-Track Multidisciplinary Clinic Integrating Movement Disorders Neurologists in Normal Pressure Hydrocephalus Evaluation.

Author: Alhusaini S, Sine K, Prakash P, Korthauer LE, Margolis SA, Chen A, Rawnsley N, Breen E, Vinacco K, Weisbach E, Guglielmo M, Akbar U, Davis JD, Svokos K, and Klinge P
Abstract: In this prospective observational cohort study, we provide preliminary findings from a same-day multidisciplinary fast-tracked normal pressure hydrocephalus (NPH) clinic; incorporating the expertise of movement disorders neurologists, emphasizing the clinical characteristics, consensus classification, and management of patients referred for suspected NPH. We evaluated 111 patients (male/female: 67/44) from April 2022 to May 2023. Based on the multidisciplinary team consensus, 52 (46.8%) were classified as "probable" idiopathic NPH (iNPH), 14 (12.6%) as "possible" NPH, 42 (37.8%) as "unlikely" NPH, and three (2.7%) as secondary NPH. While parkinsonian syndromes were recognized in 19.2% of "probable" iNPH patients (vs. 7.1% in "possible" and 26.2% in "unlikely" NPH), no significant group differences were noted in the scores of the UPDRS-III scale. Degenerative spine pathologies were prevalent across all NPH categories, affecting at least 50% of patients. In the "probable" iNPH group, 78.8% received programmable ventriculoperitoneal shunts, with clinical improvement identified in 87.8% at 12-month follow-up. Our findings underscore the high prevalence of overlapping and competing movement and spinal disorders in patients with suspected NPH. Further, our novel approach, incorporating movement disorder neurologists in NPH multidisciplinary evaluation, improved diagnostic precision and streamlined personalized plans, including further neurological workups, necessary spinal interventions, and medical management or rehabilitation.
Published: 2024
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43. Autopsy-Proven "Pure" Parkinson's Disease with Rapidly Progressive Dementia and Cognitive Fluctuations in a Patient with GBA Mutation.

Author: Mohammadzadeh N, Punsoni M, Alhusaini S, and Friedman JH
Subjects: Humans, Female, Aged, Autopsy, Mutation, Fatal Outcome, Alzheimer Disease genetics, Brain pathology, Brain diagnostic imaging, Parkinson Disease complications, Parkinson Disease genetics, Disease Progression, Dementia, Glucosylceramidase genetics
Abstract: Background: Parkinson's disease (PD) progresses at highly variable rates in different individuals but, in general, has a fairly stable rate of progression in each patient. In cases where the decline in cognition and behavior suddenly accelerates, we usually think of co-existent Alzheimer pathology, as most demented PD patients also have Alzheimer disease (AD) changes, although not necessarily meeting criteria for a distinct pathological diagnosis of AD., Methods: Clinico-pathological case Results: A 75-year-old woman presented with a typical PD course including a good response to L-Dopa. Four years after diagnosis she developed a rapid decline in motor symptoms, severe cognitive fluctuations, and rapidly progressive dementia, dying within one year of the onset of the rapid progression., Conclusions: While most cases of Parkinson's disease dementia (PDD) show concomitant Alzheimer's pathology, the sudden acceleration of the disease does not necessarily indicate the presence of concomitant Alzheimer's disease.
Published: 2024

44. A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Author: Chen J, Ngo A, Rodríguez-Cruces R, Royer J, Caligiuri ME, Gambardella A, Concha L, Keller SS, Cendes F, Yasuda CL, Alvim MKM, Bonilha L, Gleichgerrcht E, Focke NK, Kreilkamp B, Domin M, von Podewils F, Langner S, Rummel C, Wiest R, Martin P, Kotikalapudi R, Bender B, O'Brien TJ, Sinclair B, Vivash L, Kwan P, Desmond PM, Lui E, Duma GM, Bonanni P, Ballerini A, Vaudano AE, Meletti S, Tondelli M, Alhusaini S, Doherty CP, Cavalleri GL, Delanty N, Kälviäinen R, Jackson GD, Kowalczyk M, Mascalchi M, Semmelroch M, Thomas RH, Soltanian-Zadeh H, Davoodi-Bojd E, Zhang J, Lenge M, Guerrini R, Bartolini E, Hamandi K, Foley S, Rüber T, Bauer T, Weber B, Caldairou B, Depondt C, Absil J, Carr SJA, Abela E, Richardson MP, Devinsky O, Pardoe H, Severino M, Striano P, Tortora D, Kaestner E, Hatton SN, Arienzo D, Vos SB, Ryten M, Taylor PN, Duncan JS, Whelan CD, Galovic M, Winston GP, Thomopoulos SI, Thompson PM, Sisodiya SM, Labate A, McDonald CR, Caciagli L, Bernasconi N, Bernasconi A, Larivière S, Schrader D, and Bernhardt BC
Abstract: Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments., Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves., Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions., Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.
Published: 2024
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45. Pearls & Oy-sters: Adult-Onset Craniopharyngioma Presenting With Cognitive Dysfunction and Obstructive Hydrocephalus.

Author: Schroeder LE, Kritselis M, Lala N, Boxerman J, and Alhusaini S
Subjects: Humans, Adult, Craniopharyngioma complications, Craniopharyngioma diagnostic imaging, Hydrocephalus complications, Hydrocephalus diagnostic imaging, Cognitive Dysfunction etiology, Pituitary Neoplasms diagnosis, Pituitary Neoplasms diagnostic imaging
Published: 2023
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46. Parkinsonism: A Rare Complication of Cerebral Toxoplasmosis.

Author: Mohammadzadeh N, Tung GA, Prakash P, and Alhusaini S
Subjects: Humans, Toxoplasmosis, Cerebral complications, Toxoplasmosis, Cerebral diagnostic imaging, Parkinsonian Disorders etiology, Parkinsonian Disorders complications
Published: 2023
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47. Real-world risk of brain metastases in stage III non-small cell lung cancer in the era of PET and MRI staging.

Author: Alhusaini S, Lanman TA, Ko RB, Therkelsen KE, Eyben RV, Diehn M, Soltys SG, Pollom EL, Chin A, Vitzthum L, Wakelee HA, Padda SK, Ramchandran K, Loo BW Jr, Neal JW, and Nagpal S
Abstract: Objective: The 2-year incidence of brain metastases (BrMs) in stage III non-small lung cell cancer (NSCLC) has been estimated to be around 30%. However, recent clinical trials have demonstrated considerably lower BrMs rates in this patient population. In this study, we aimed to review the real-world incidence, surveillance, and treatment patterns of BrMs in stage III NSCLC., Materials and Methods: Using a retrospective single-center study design, we identified patients with stage III NSCLC who received radiation with curative intent over a 10-year period. Outcome variables included BrMs incidence, overall survival (OS), and survival from date of BrMs. Additionally, we assessed patterns of BrMs surveillance in stage III NSCLC and treatment., Results: We identified a total of 279 stage III NSCLC patients, of which 160 with adequate records were included in the final analyses [adenocarcinoma (n = 96), squamous cell carcinoma (n = 53), other histology subtype (n = 11)]. The median OS for the entire cohort was 41 months (95% CI, 28-53), while the median time from BrMs to death was 19 months (95% CI, 9-21). Twenty-three patients (14.4%) received planned surveillance brain MRIs at 6, 12, and 24 months after completion of treatment. The remaining 137 patients (85.6%) received brain MRIs at systemic recurrence (restaging) or when neurologically symptomatic. A total of 37 patients (23%) developed BrMs, with a 2-year cumulative BrMs incidence of 17% (95% CI, 11-23). A higher incidence of BrMs was identified in patients with adenocarcinoma relative to those with squamous cell carcinoma ( p < 0.01). Similarly, a higher 2-year BrMs incidence was observed in patients who received planned surveillance brain MRI relative to those who did not, although statistical significance was not reached. Stereotactic radiosurgery (SRS) treated 29 of BrMs patients (78.4%) and was preferred over WBRT, which treated only 3 patients (8.1%)., Conclusions: At our center, BrMs incidence in stage III NSCLC patients was lower than historically reported but notably higher than the incidence described in recent clinical trials. Routine BrMs surveillance potentially allows earlier detection of asymptomatic BrMs. However, asymptomatic BrMs were mostly detected on restaging MRI at the time of recurrence., Competing Interests: Author SS: Speaker Honoraria, Zap Surgical, Inc and consultant at Accuray, Inc. EP: Board, Vysioneer. HW: President of International Association for the Study of Lung Cancer IASLC. Executive committee member of ECOG-ACRIN. Advisory Board, AstraZeneca, Janssen, Daiichi Sankyo, Blueprint, Mirati, Merck, Genentech/Roche. BL: Co-founder and board member of TibaRay. Research support from Varian Medical Systems. JN: Consulting or Advisory Role: AstraZeneca, Genentech/Roche, Exelixis, Jounce Therapeutics, Takeda Pharmaceuticals, Eli Lilly and Company, Calithera Biosciences, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, Natera, Sanofi/Regeneron, D2G Oncology, Surface Oncology, Turning Point Therapeutics. SN: Consulting Role, Mirati, SeaGen, Biocept. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author SS received research funding from Novocure, Inc. EP received research funding from Genentech. HW received research funding from ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune, BMS, Clovis Oncology, Genentech/Roche, Merck, Novartis, SeaGen, Xcovery, Helsinn. BL received research funding from Varian Medical Systems. JN received research funding from Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GSK, Janssen, AbbVie. SN received research funding from Novocure, PharmAbcine, Berg Health, Agios, Pyramid Biosciences, ABM Therapuetics., (Copyright © 2023 Alhusaini, Lanman, Ko, Therkelsen, Eyben, Diehn, Soltys, Pollom, Chin, Vitzthum, Wakelee, Padda, Ramchandran, Loo, Neal and Nagpal.)
Published: 2023
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48. Event-based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data.

Author: Lopez SM, Aksman LM, Oxtoby NP, Vos SB, Rao J, Kaestner E, Alhusaini S, Alvim M, Bender B, Bernasconi A, Bernasconi N, Bernhardt B, Bonilha L, Caciagli L, Caldairou B, Caligiuri ME, Calvet A, Cendes F, Concha L, Conde-Blanco E, Davoodi-Bojd E, de Bézenac C, Delanty N, Desmond PM, Devinsky O, Domin M, Duncan JS, Focke NK, Foley S, Fortunato F, Galovic M, Gambardella A, Gleichgerrcht E, Guerrini R, Hamandi K, Ives-Deliperi V, Jackson GD, Jahanshad N, Keller SS, Kochunov P, Kotikalapudi R, Kreilkamp BAK, Labate A, Larivière S, Lenge M, Lui E, Malpas C, Martin P, Mascalchi M, Medland SE, Meletti S, Morita-Sherman ME, Owen TW, Richardson M, Riva A, Rüber T, Sinclair B, Soltanian-Zadeh H, Stein DJ, Striano P, Taylor PN, Thomopoulos SI, Thompson PM, Tondelli M, Vaudano AE, Vivash L, Wang Y, Weber B, Whelan CD, Wiest R, Winston GP, Yasuda CL, McDonald CR, Alexander DC, Sisodiya SM, and Altmann A
Subjects: Atrophy pathology, Biomarkers, Cross-Sectional Studies, Hippocampus diagnostic imaging, Hippocampus pathology, Humans, Magnetic Resonance Imaging methods, Sclerosis complications, Epilepsy complications, Epilepsy, Temporal Lobe pathology
Abstract: Objective: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features., Methods: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1-weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers. Features with a moderate case-control effect size (Cohen d ≥ .5) were used to train an event-based model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance., Results: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10 -16 ), age at onset (ρ = -.18, p = 9.82 × 10 -7 ), and ASM resistance (area under the curve = .59, p = .043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE-HS with mild or nondetectable abnormality on T1W MRI., Significance: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Published: 2022
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49. Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression.

Author: Larivière S, Royer J, Rodríguez-Cruces R, Paquola C, Caligiuri ME, Gambardella A, Concha L, Keller SS, Cendes F, Yasuda CL, Bonilha L, Gleichgerrcht E, Focke NK, Domin M, von Podewills F, Langner S, Rummel C, Wiest R, Martin P, Kotikalapudi R, O'Brien TJ, Sinclair B, Vivash L, Desmond PM, Lui E, Vaudano AE, Meletti S, Tondelli M, Alhusaini S, Doherty CP, Cavalleri GL, Delanty N, Kälviäinen R, Jackson GD, Kowalczyk M, Mascalchi M, Semmelroch M, Thomas RH, Soltanian-Zadeh H, Davoodi-Bojd E, Zhang J, Winston GP, Griffin A, Singh A, Tiwari VK, Kreilkamp BAK, Lenge M, Guerrini R, Hamandi K, Foley S, Rüber T, Weber B, Depondt C, Absil J, Carr SJA, Abela E, Richardson MP, Devinsky O, Severino M, Striano P, Tortora D, Kaestner E, Hatton SN, Vos SB, Caciagli L, Duncan JS, Whelan CD, Thompson PM, Sisodiya SM, Bernasconi A, Labate A, McDonald CR, Bernasconi N, and Bernhardt BC
Subjects: Adult, Gene Expression, Humans, Immunoglobulin E, Magnetic Resonance Imaging, Nerve Net, Connectome, Epilepsy, Epilepsy, Generalized genetics, Epilepsy, Temporal Lobe diagnosis, Epilepsy, Temporal Lobe genetics
Abstract: Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes., (© 2022. The Author(s).)
Published: 2022
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50. SCN1A overexpression, associated with a genomic region marked by a risk variant for a common epilepsy, raises seizure susceptibility.

Author: Silvennoinen K, Gawel K, Tsortouktzidis D, Pitsch J, Alhusaini S, van Loo KMJ, Picardo R, Michalak Z, Pagni S, Martins Custodio H, Mills J, Whelan CD, de Zubicaray GI, McMahon KL, van der Ent W, Kirstein-Smardzewska KJ, Tiraboschi E, Mudge JM, Frankish A, Thom M, Wright MJ, Thompson PM, Schoch S, Becker AJ, Esguerra CV, and Sisodiya SM
Subjects: Animals, Genomics, Gliosis pathology, Hippocampus pathology, Humans, NAV1.1 Voltage-Gated Sodium Channel genetics, Sclerosis pathology, Zebrafish, Epilepsy genetics, Epilepsy, Temporal Lobe genetics, NAV1.1 Voltage-Gated Sodium Channel metabolism, Seizures, Febrile complications, Seizures, Febrile genetics, Zebrafish Proteins metabolism
Abstract: Mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures is associated with common variation at rs7587026, located in the promoter region of SCN1A. We sought to explore possible underlying mechanisms. SCN1A expression was analysed in hippocampal biopsy specimens of individuals with mesial temporal lobe epilepsy with hippocampal sclerosis who underwent surgical treatment, and hippocampal neuronal cell loss was quantitatively assessed using immunohistochemistry. In healthy individuals, hippocampal volume was measured using MRI. Analyses were performed stratified by rs7587026 type. To study the functional consequences of increased SCN1A expression, we generated, using transposon-mediated bacterial artificial chromosome transgenesis, a zebrafish line expressing exogenous scn1a, and performed EEG analysis on larval optic tecta at 4 day post-fertilization. Finally, we used an in vitro promoter analysis to study whether the genetic motif containing rs7587026 influences promoter activity. Hippocampal SCN1A expression differed by rs7587026 genotype (Kruskal-Wallis test P = 0.004). Individuals homozygous for the minor allele showed significantly increased expression compared to those homozygous for the major allele (Dunn's test P = 0.003), and to heterozygotes (Dunn's test P = 0.035). No statistically significant differences in hippocampal neuronal cell loss were observed between the three genotypes. Among 597 healthy participants, individuals homozygous for the minor allele at rs7587026 displayed significantly reduced mean hippocampal volume compared to major allele homozygotes (Cohen's D = - 0.28, P = 0.02), and to heterozygotes (Cohen's D = - 0.36, P = 0.009). Compared to wild type, scn1lab-overexpressing zebrafish larvae exhibited more frequent spontaneous seizures [one-way ANOVA F(4,54) = 6.95 (P < 0.001)]. The number of EEG discharges correlated with the level of scn1lab overexpression [one-way ANOVA F(4,15) = 10.75 (P < 0.001]. Finally, we showed that a 50 bp promoter motif containing rs7587026 exerts a strong regulatory role on SCN1A expression, though we could not directly link this to rs7587026 itself. Our results develop the mechanistic link between rs7587026 and mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures. Furthermore, we propose that quantitative precision may be important when increasing SCN1A expression in current strategies aiming to treat seizures in conditions involving SCN1A haploinsufficiency, such as Dravet syndrome., (© 2022. The Author(s).)
Published: 2022
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