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110 results on '"Steen, V.M."'

4. Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Author

Lam, M. Chen, C.-Y. Ge, T. Xia, Y. Hill, D.W. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Stahl, E.A. Huckins, L. Liewald, D.C. Djurovic, S. Melle, I. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Hartmann, A.M. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Koltai, D.C. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Smyrnis, N. Bilder, R.M. Freimer, N.B. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Huang, H. Liu, C. Malhotra, A.K. Lencz, T.

Abstract

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing. © 2021, The Author(s).

Published
2021

5. Genetic control of variability in subcortical and intracranial volumes

Author

Córdova-Palomera, A., Meer, D. van der, Kaufmann, T., Bettella, F., Wang, Y., Alnæs, D., Doan, N.T., Agartz, I., Bertolino, A., Buitelaar, J.K., Coynel, D., Djurovic, S., Dørum, E.S., Espeseth, T., Fazio, L., Franke, B., Frei, O., Håberg, A., Hellard, S. Le, Jönsson, E.G., Kolskår, K.K., Lund, M.J., Moberget, T., Nordvik, J.E., Nyberg, L., Papassotiropoulos, A., Pergola, G., Quervain, D. de, Rampino, A., Richard, G., Rokicki, J., Sanders, A.M., Schwarz, E., Smeland, O.B., Steen, V.M., Starrfelt, J., Sønderby, I.E., Ulrichsen, K.M., Andreassen, O.A., Westlye, L.T., Córdova-Palomera, A., Meer, D. van der, Kaufmann, T., Bettella, F., Wang, Y., Alnæs, D., Doan, N.T., Agartz, I., Bertolino, A., Buitelaar, J.K., Coynel, D., Djurovic, S., Dørum, E.S., Espeseth, T., Fazio, L., Franke, B., Frei, O., Håberg, A., Hellard, S. Le, Jönsson, E.G., Kolskår, K.K., Lund, M.J., Moberget, T., Nordvik, J.E., Nyberg, L., Papassotiropoulos, A., Pergola, G., Quervain, D. de, Rampino, A., Richard, G., Rokicki, J., Sanders, A.M., Schwarz, E., Smeland, O.B., Steen, V.M., Starrfelt, J., Sønderby, I.E., Ulrichsen, K.M., Andreassen, O.A., and Westlye, L.T.

Abstract

Item does not contain fulltext, Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.

Published
2021

6. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author

Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Andreassen, O.A., Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., and Andreassen, O.A.

Abstract

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Published
2021

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

Author

Sønderby, I.E., Gústafsson, Ó., Doan, N.T., Hibar, D.P., Martin-Brevet, S., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N., Blangero, J., Boomsma, D.I., Bralten, J., Brattbak, H-R, Brodaty, H., Brouwer, R.M., Bülow, R., Calhoun, V., Caspers, S., Cavalleri, G., Chen, C-H, Cichon, S., Ciufolini, S., Corvin, A., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Delanty, N., den Braber, A., Desrivières, S., Donohoe, G., Draganski, B., Ehrlich, S., Espeseth, T., Fisher, S.E., Franke, B., Frouin, V., Fukunaga, M., Gareau, T., Glahn, D.C., Grabe, H., Groenewold, N.A., Haavik, J., Håberg, A., Hashimoto, R., Hehir-Kwa, J.Y., Heinz, A., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Hottenga, J-J, Hulshoff, H.E., Ikeda, M., Jahanshad, N., Jernigan, T., Jockwitz, C., Johansson, S., Jonsdottir, G.A., Jönsson, E.G., Kahn, R., Kaufmann, T., Kelly, S., Kikuchi, M., Knowles, E.E.M., Kolskår, K.K., Kwok, J.B., Hellard, S.L., Leu, C., Liu, J., Lundervold, A.J., Lundervold, A., Martin, N.G., Mather, K., Mathias, S.R., McCormack, M., McMahon, K.L., McRae, A., Milaneschi, Y., Moreau, C., Morris, D., Mothersill, D., Mühleisen, T.W., Murray, R., Nordvik, J.E., Nyberg, L., Olde Loohuis, L.M., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Peralta, J.M., Pike, B., Prieto, C., Pudas, S., Quinlan, E., Quintana, D.S., Reinbold, C.S., Marques, T.R., Reymond, A., Richard, G., Rodriguez-Herreros, B., Roiz-Santiañez, R., Rokicki, J., Rucker, J., Sachdev, P., Sanders, A-M, Sando, S.B., Schmaal, L., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Sisodiya, S., Steen, V.M., Stein, D.J., Steinberg, S., Strike, L., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J., Ueland, T., Uhlmann, A., Ulfarsson, M.O., van ’t Ent, D., van der Meer, D., van Haren, N.E.M., Vaskinn, A., Vassos, E., Walters, G.B., Wang, Y., Wen, W., Whelan, C.D., Wittfeld, K., Wright, M., Yamamori, H., Zayats, T., Agartz, I., Westlye, L.T., Jacquemont, S., Djurovic, S., Stefánsson, H., Stefánsson, K., Thompson, P., Andreassen, O.A., Sønderby, I.E., Gústafsson, Ó., Doan, N.T., Hibar, D.P., Martin-Brevet, S., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N., Blangero, J., Boomsma, D.I., Bralten, J., Brattbak, H-R, Brodaty, H., Brouwer, R.M., Bülow, R., Calhoun, V., Caspers, S., Cavalleri, G., Chen, C-H, Cichon, S., Ciufolini, S., Corvin, A., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Delanty, N., den Braber, A., Desrivières, S., Donohoe, G., Draganski, B., Ehrlich, S., Espeseth, T., Fisher, S.E., Franke, B., Frouin, V., Fukunaga, M., Gareau, T., Glahn, D.C., Grabe, H., Groenewold, N.A., Haavik, J., Håberg, A., Hashimoto, R., Hehir-Kwa, J.Y., Heinz, A., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Hottenga, J-J, Hulshoff, H.E., Ikeda, M., Jahanshad, N., Jernigan, T., Jockwitz, C., Johansson, S., Jonsdottir, G.A., Jönsson, E.G., Kahn, R., Kaufmann, T., Kelly, S., Kikuchi, M., Knowles, E.E.M., Kolskår, K.K., Kwok, J.B., Hellard, S.L., Leu, C., Liu, J., Lundervold, A.J., Lundervold, A., Martin, N.G., Mather, K., Mathias, S.R., McCormack, M., McMahon, K.L., McRae, A., Milaneschi, Y., Moreau, C., Morris, D., Mothersill, D., Mühleisen, T.W., Murray, R., Nordvik, J.E., Nyberg, L., Olde Loohuis, L.M., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Peralta, J.M., Pike, B., Prieto, C., Pudas, S., Quinlan, E., Quintana, D.S., Reinbold, C.S., Marques, T.R., Reymond, A., Richard, G., Rodriguez-Herreros, B., Roiz-Santiañez, R., Rokicki, J., Rucker, J., Sachdev, P., Sanders, A-M, Sando, S.B., Schmaal, L., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Sisodiya, S., Steen, V.M., Stein, D.J., Steinberg, S., Strike, L., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J., Ueland, T., Uhlmann, A., Ulfarsson, M.O., van ’t Ent, D., van der Meer, D., van Haren, N.E.M., Vaskinn, A., Vassos, E., Walters, G.B., Wang, Y., Wen, W., Whelan, C.D., Wittfeld, K., Wright, M., Yamamori, H., Zayats, T., Agartz, I., Westlye, L.T., Jacquemont, S., Djurovic, S., Stefánsson, H., Stefánsson, K., Thompson, P., and Andreassen, O.A.

Abstract

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.

Published
2020

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

Author

Elvsåshagen, T., Bahrami, S., Meer, D. van der, Agartz, I., Alnæs, D., Barch, D.M., Baur-Streubel, R., Bertolino, A., Beyer, M.K., Blasi, G., Borgwardt, S., Boye, B., Buitelaar, J.K., Bøen, E., Celius, E.G., Cervenka, S., Conzelmann, A., Coynel, D., Carlo, P. di, Djurovic, S., Eisenacher, S., Espeseth, T., Fatouros-Bergman, H., Flyckt, L., Franke, B., Frei, O., Gelao, B., Harbo, H.F., Hartman, Catharina A., Håberg, A., Heslenfeld, D., Hoekstra, P.J., Høgestøl, E.A., Jonassen, R., Jönsson, E.G., Kirsch, P., Kłoszewska, I., Lagerberg, T.V., Landrø, N.I., Hellard, S. Le, Lesch, K.P., Maglanoc, L.A., Malt, U.F., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Moberget, T., Nordvik, J.E., Nyberg, L., Connell, K.S.O., Oosterlaan, J., Papalino, M., Papassotiropoulos, A., Pauli, P., Pergola, G., Persson, K., Quervain, D. de, Reif, A., Rokicki, J., Rooij, D. van, Shadrin, A.A., Schmidt, A., Schwarz, E., Selbæk, G., Soininen, H., Sowa, P., Steen, V.M., Tsolaki, M., Vellas, B., Wang, L, Westman, E., Ziegler, G.C., Zink, M., Andreassen, O.A., Westlye, L.T., Kaufmann, T., Elvsåshagen, T., Bahrami, S., Meer, D. van der, Agartz, I., Alnæs, D., Barch, D.M., Baur-Streubel, R., Bertolino, A., Beyer, M.K., Blasi, G., Borgwardt, S., Boye, B., Buitelaar, J.K., Bøen, E., Celius, E.G., Cervenka, S., Conzelmann, A., Coynel, D., Carlo, P. di, Djurovic, S., Eisenacher, S., Espeseth, T., Fatouros-Bergman, H., Flyckt, L., Franke, B., Frei, O., Gelao, B., Harbo, H.F., Hartman, Catharina A., Håberg, A., Heslenfeld, D., Hoekstra, P.J., Høgestøl, E.A., Jonassen, R., Jönsson, E.G., Kirsch, P., Kłoszewska, I., Lagerberg, T.V., Landrø, N.I., Hellard, S. Le, Lesch, K.P., Maglanoc, L.A., Malt, U.F., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Moberget, T., Nordvik, J.E., Nyberg, L., Connell, K.S.O., Oosterlaan, J., Papalino, M., Papassotiropoulos, A., Pauli, P., Pergola, G., Persson, K., Quervain, D. de, Reif, A., Rokicki, J., Rooij, D. van, Shadrin, A.A., Schmidt, A., Schwarz, E., Selbæk, G., Soininen, H., Sowa, P., Steen, V.M., Tsolaki, M., Vellas, B., Wang, L, Westman, E., Ziegler, G.C., Zink, M., Andreassen, O.A., Westlye, L.T., and Kaufmann, T.

Abstract

Contains fulltext : 225402.pdf (publisher's version ) (Open Access), Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.

Published
2020

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.K., McMahon, M.A.B., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A.A., Alnæs, D., Amlien, I.K., Andersson, M., Ard, T., Armstrong, N.J., Ashley-Koch, A., Atkins, J.R., Bernard, M., Brouwer, R.M., Buimer, E.E.L., Bülow, R., Bürger, C., Cannon, D.M., Chakravarty, M.M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., de Araujo, T.K., de Zubicaray, G.I., de Zwarte, S.M.C., den Braber, A., Doan, N.T., Dohm, K., Ehrlich, S., Engelbrecht, H-R, Erk, S., Fan, C.C., Fedko, I.O., Foley, S.F., Ford, J.M., Fukunaga, M., Garrett, M.E., Ge, T., Giddaluru, S., Goldman, A.L., Green, M.J., Groenewold, N.A., Grotegerd, D., Gurholt, T.P., Gutman, B.A., Hansell, N.K., Harris, M.A., Harrison, M.B., Haswell, C.C., Hauser, M., Herms, S., Heslenfeld, D.J., Ho, N.F., Hoehn, D., Hoffmann, P., Holleran, L., Hoogman, M., Hottenga, J-J, Ikeda, M., Janowitz, D., Jansen, I.E., Jia, T., Jockwitz, C., Kanai, R., Karama, S., Kasperaviciute, D., Kaufmann, T., Kelly, S., Kikuchi, M., Klein, M., Knapp, M., Knodt, A.R., Krämer, B., Lam, M., Lancaster, T.M., Lee, P.H., Lett, T.A., Lewis, L.B., Lopes-Cendes, I., Luciano, M., Macciardi, F., Marquand, A.F., Mathias, S.R., Melzer, T.R., Milaneschi, Y., Mirza-Schreiber, N., Moreira, J.C.V., Mühleisen, T.W., Müller-Myhsok, B., Najt, P., Nakahara, S., Nho, K., Olde Loohuis, L.M., Orfanos, D.P., Pearson, J.F., Pitcher, T.L., Pütz, B., Quidé, Y., Ragothaman, A., Rashid, F.M., Reay, W.R., Redlich, R., Reinbold, C.S., Repple, J., Richard, G., Riedel, B.C., Risacher, S.L., Rocha, C.S., Mota, N.R., Salminen, L., Saremi, A., Saykin, A.J., Schlag, F., Schmaal, L., Schofield, P.R., Secolin, R., Shapland, C.Y., Shen, L., Shin, J., Shumskaya, E., Sønderby, I.E., Sprooten, E., Tansey, K.E., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.A., Uhlmann, A., Vallerga, C.L., van der Meer, D., van Donkelaar, M.M.J., van Eijk, L., Van Erp, T.G.M., van Haren, N.E.M., Van Rooij, D., van Tol, M-J, Veldink, J.H., Verhoef, E., Walton, E., Wang, M., Wang, Y., Wardlaw, J.M., Wen, W., Westlye, L.T., Whelan, C.D., Witt, S.H., Wittfeld, K., Wolf, C., Wolfers, T., Wu, J.Q., Yasuda, C.L., Zaremba, D., Zhang, Z., Zwiers, M.P., Artiges, E., Assareh, A.A., Ayesa-Arriola, R., Belger, A., Brandt, C.L., Brown, G.G., Cichon, S., Curran, J.E., Davies, G.E., Degenhardt, F., Dennis, M.F., Dietsche, B., Djurovic, S., Doherty, C.P., Espiritu, R., Garijo, D., Gil, Y., Gowland, P.A., Green, R.C., Häusler, A.N., Heindel, W., Ho, B-C., Hoffmann, W.U., Holsboer, F., Homuth, G., Hosten, N., Jack, C.R., Jang, M., Jansen, A., Kimbrel, N.A., Kolskår, K., Koops, S., Krug, A., Lim, K.O., Luykx, J.J., Mathalon, D.H., Mather, K.A., Mattay, V.S., Matthews, S., Mayoral Van Son, J., McEwen, S.C., Melle, I., Morris, D.W., Mueller, B.A., Nauck, M., Nordvik, J.E., Nöthen, M.M., O’Leary, D.S., Opel, N., Martinot, M-L.P., Pike, G.B., Preda, A., Quinlan, E.B., Rasser, P.E., Ratnakar, V., Reppermund, S., Steen, V.M., Tooney, P.A., Torres, F.R., Veltman, D.J., Voyvodic, J.T., Whelan, R., White, T., Yamamori, H., Adams, H.H.H., Bis, J.C., Debette, S., DeCarli, C., Fornage, M., Gudnason, V., Hofer, E., Ikram, M.A., Launer, L., Longstreth, W.T., Lopez, O.L., Mazoyer, B., Mosley, T.H., Roshchupkin, G.V., Satizabal, C.L., Schmidt, R., Seshadri, S., Yang, Q., Alvim, M.K.M., Ames, D., Anderson, T.J., Andreassen, O.A., Arias-Vasquez, A., Bastin, M.E., Baune, B.T., Beckham, J.C., Blangero, J., Boomsma, D.I., Brodaty, H., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bustillo, J.R., Cahn, W., Cairns, M.J., Calhoun, V., Carr, V.J., Caseras, X., Caspers, S., Cavalleri, G.L., Cendes, F., Corvin, A., Crespo-Facorro, B., Dalrymple-Alford, J.C., Dannlowski, U., de Geus, E.J.C., Deary, I.J., Delanty, N., Depondt, C., Desrivières, S., Donohoe, G., Espeseth, T., Fernández, G., Fisher, S.E., Flor, H., Forstner, A.J., Francks, C., Franke, B., Glahn, D.C., Gollub, R.L., Grabe, H.J., Gruber, O., Håberg, A.K., Hariri, A.R., Hartman, C.A., Hashimoto, R., Heinz, A., Henskens, F.A., Hillegers, M.H.J., Hoekstra, P.J., Holmes, A.J., Hong, L.E., Hopkins, W.D., Hulshoff Pol, H.E., Jernigan, T.L., Jönsson, E.G., Kahn, R.S., Kennedy, M.A., Kircher, T.T.J., Kochunov, P., Kwok, J.B.J., Le Hellard, S., Loughland, C.M., Martin, N.G., Martinot, J-L, McDonald, C., McMahon, K.L., Meyer-Lindenberg, A., Michie, P.T., Morey, R.A., Mowry, B., Nyberg, L., Oosterlaan, J., Ophoff, R.A., Pantelis, C., Paus, T., Pausova, Z., Penninx, B.W.J.H., Polderman, T.J.C., Posthuma, D., Rietschel, M., Roffman, J.L., Rowland, L.M., Sachdev, P.S., Sämann, P.G., Schall, U., Schumann, G., Scott, R.J., Sim, K., Sisodiya, S.M., Smoller, J.W., Sommer, I.E., St Pourcain, B., Stein, D.J., Toga, A.W., Trollor, J.N., van der Wee, N.J.A., van ’t Ent, D., Völzke, H., Walter, H., Weber, B., Weinberger, D.R., Wright, M.J., Zhou, J., Stein, J.L., Thompson, P.M., Medland, S.E., Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Ching, C.R.K., McMahon, M.A.B., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A.A., Alnæs, D., Amlien, I.K., Andersson, M., Ard, T., Armstrong, N.J., Ashley-Koch, A., Atkins, J.R., Bernard, M., Brouwer, R.M., Buimer, E.E.L., Bülow, R., Bürger, C., Cannon, D.M., Chakravarty, M.M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., de Araujo, T.K., de Zubicaray, G.I., de Zwarte, S.M.C., den Braber, A., Doan, N.T., Dohm, K., Ehrlich, S., Engelbrecht, H-R, Erk, S., Fan, C.C., Fedko, I.O., Foley, S.F., Ford, J.M., Fukunaga, M., Garrett, M.E., Ge, T., Giddaluru, S., Goldman, A.L., Green, M.J., Groenewold, N.A., Grotegerd, D., Gurholt, T.P., Gutman, B.A., Hansell, N.K., Harris, M.A., Harrison, M.B., Haswell, C.C., Hauser, M., Herms, S., Heslenfeld, D.J., Ho, N.F., Hoehn, D., Hoffmann, P., Holleran, L., Hoogman, M., Hottenga, J-J, Ikeda, M., Janowitz, D., Jansen, I.E., Jia, T., Jockwitz, C., Kanai, R., Karama, S., Kasperaviciute, D., Kaufmann, T., Kelly, S., Kikuchi, M., Klein, M., Knapp, M., Knodt, A.R., Krämer, B., Lam, M., Lancaster, T.M., Lee, P.H., Lett, T.A., Lewis, L.B., Lopes-Cendes, I., Luciano, M., Macciardi, F., Marquand, A.F., Mathias, S.R., Melzer, T.R., Milaneschi, Y., Mirza-Schreiber, N., Moreira, J.C.V., Mühleisen, T.W., Müller-Myhsok, B., Najt, P., Nakahara, S., Nho, K., Olde Loohuis, L.M., Orfanos, D.P., Pearson, J.F., Pitcher, T.L., Pütz, B., Quidé, Y., Ragothaman, A., Rashid, F.M., Reay, W.R., Redlich, R., Reinbold, C.S., Repple, J., Richard, G., Riedel, B.C., Risacher, S.L., Rocha, C.S., Mota, N.R., Salminen, L., Saremi, A., Saykin, A.J., Schlag, F., Schmaal, L., Schofield, P.R., Secolin, R., Shapland, C.Y., Shen, L., Shin, J., Shumskaya, E., Sønderby, I.E., Sprooten, E., Tansey, K.E., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.A., Uhlmann, A., Vallerga, C.L., van der Meer, D., van Donkelaar, M.M.J., van Eijk, L., Van Erp, T.G.M., van Haren, N.E.M., Van Rooij, D., van Tol, M-J, Veldink, J.H., Verhoef, E., Walton, E., Wang, M., Wang, Y., Wardlaw, J.M., Wen, W., Westlye, L.T., Whelan, C.D., Witt, S.H., Wittfeld, K., Wolf, C., Wolfers, T., Wu, J.Q., Yasuda, C.L., Zaremba, D., Zhang, Z., Zwiers, M.P., Artiges, E., Assareh, A.A., Ayesa-Arriola, R., Belger, A., Brandt, C.L., Brown, G.G., Cichon, S., Curran, J.E., Davies, G.E., Degenhardt, F., Dennis, M.F., Dietsche, B., Djurovic, S., Doherty, C.P., Espiritu, R., Garijo, D., Gil, Y., Gowland, P.A., Green, R.C., Häusler, A.N., Heindel, W., Ho, B-C., Hoffmann, W.U., Holsboer, F., Homuth, G., Hosten, N., Jack, C.R., Jang, M., Jansen, A., Kimbrel, N.A., Kolskår, K., Koops, S., Krug, A., Lim, K.O., Luykx, J.J., Mathalon, D.H., Mather, K.A., Mattay, V.S., Matthews, S., Mayoral Van Son, J., McEwen, S.C., Melle, I., Morris, D.W., Mueller, B.A., Nauck, M., Nordvik, J.E., Nöthen, M.M., O’Leary, D.S., Opel, N., Martinot, M-L.P., Pike, G.B., Preda, A., Quinlan, E.B., Rasser, P.E., Ratnakar, V., Reppermund, S., Steen, V.M., Tooney, P.A., Torres, F.R., Veltman, D.J., Voyvodic, J.T., Whelan, R., White, T., Yamamori, H., Adams, H.H.H., Bis, J.C., Debette, S., DeCarli, C., Fornage, M., Gudnason, V., Hofer, E., Ikram, M.A., Launer, L., Longstreth, W.T., Lopez, O.L., Mazoyer, B., Mosley, T.H., Roshchupkin, G.V., Satizabal, C.L., Schmidt, R., Seshadri, S., Yang, Q., Alvim, M.K.M., Ames, D., Anderson, T.J., Andreassen, O.A., Arias-Vasquez, A., Bastin, M.E., Baune, B.T., Beckham, J.C., Blangero, J., Boomsma, D.I., Brodaty, H., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bustillo, J.R., Cahn, W., Cairns, M.J., Calhoun, V., Carr, V.J., Caseras, X., Caspers, S., Cavalleri, G.L., Cendes, F., Corvin, A., Crespo-Facorro, B., Dalrymple-Alford, J.C., Dannlowski, U., de Geus, E.J.C., Deary, I.J., Delanty, N., Depondt, C., Desrivières, S., Donohoe, G., Espeseth, T., Fernández, G., Fisher, S.E., Flor, H., Forstner, A.J., Francks, C., Franke, B., Glahn, D.C., Gollub, R.L., Grabe, H.J., Gruber, O., Håberg, A.K., Hariri, A.R., Hartman, C.A., Hashimoto, R., Heinz, A., Henskens, F.A., Hillegers, M.H.J., Hoekstra, P.J., Holmes, A.J., Hong, L.E., Hopkins, W.D., Hulshoff Pol, H.E., Jernigan, T.L., Jönsson, E.G., Kahn, R.S., Kennedy, M.A., Kircher, T.T.J., Kochunov, P., Kwok, J.B.J., Le Hellard, S., Loughland, C.M., Martin, N.G., Martinot, J-L, McDonald, C., McMahon, K.L., Meyer-Lindenberg, A., Michie, P.T., Morey, R.A., Mowry, B., Nyberg, L., Oosterlaan, J., Ophoff, R.A., Pantelis, C., Paus, T., Pausova, Z., Penninx, B.W.J.H., Polderman, T.J.C., Posthuma, D., Rietschel, M., Roffman, J.L., Rowland, L.M., Sachdev, P.S., Sämann, P.G., Schall, U., Schumann, G., Scott, R.J., Sim, K., Sisodiya, S.M., Smoller, J.W., Sommer, I.E., St Pourcain, B., Stein, D.J., Toga, A.W., Trollor, J.N., van der Wee, N.J.A., van ’t Ent, D., Völzke, H., Walter, H., Weber, B., Weinberger, D.R., Wright, M.J., Zhou, J., Stein, J.L., Thompson, P.M., and Medland, S.E.

Abstract

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When co

Published
2020

11. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018)

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., Lee, S.J. van der, Ware, E.B., Windham, B.G., Wright, M.J., Yang, J.Y., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Bohmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kahonen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Hellard, S. le, Lee, T., Lehtimaki, T., Li, S.C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikainen, L.P., Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumare, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., Jager, P.L. de, Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hagg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Raikkonen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., Duijn, C.M. van, Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Published
2019

12. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (Nature Communications, (2018), 9, 1, (2098), 10.1038/s41467-018-04362-x)

Author

Davies, G. Lam, M. Harris, S.E. Trampush, J.W. Luciano, M. Hill, W.D. Hagenaars, S.P. Ritchie, S.J. Marioni, R.E. Fawns-Ritchie, C. Liewald, D.C.M. Okely, J.A. Ahola-Olli, A.V. Barnes, C.L.K. Bertram, L. Bis, J.C. Burdick, K.E. Christoforou, A. DeRosse, P. Djurovic, S. Espeseth, T. Giakoumaki, S. Giddaluru, S. Gustavson, D.E. Hayward, C. Hofer, E. Ikram, M.A. Karlsson, R. Knowles, E. Lahti, J. Leber, M. Li, S. Mather, K.A. Melle, I. Morris, D. Oldmeadow, C. Palviainen, T. Payton, A. Pazoki, R. Petrovic, K. Reynolds, C.A. Sargurupremraj, M. Scholz, M. Smith, J.A. Smith, A.V. Terzikhan, N. Thalamuthu, A. Trompet, S. van der Lee, S.J. Ware, E.B. Windham, B.G. Wright, M.J. Yang, J. Yu, J. Ames, D. Amin, N. Amouyel, P. Andreassen, O.A. Armstrong, N.J. Assareh, A.A. Attia, J.R. Attix, D. Avramopoulos, D. Bennett, D.A. Böhmer, A.C. Boyle, P.A. Brodaty, H. Campbell, H. Cannon, T.D. Cirulli, E.T. Congdon, E. Conley, E.D. Corley, J. Cox, S.R. Dale, A.M. Dehghan, A. Dick, D. Dickinson, D. Eriksson, J.G. Evangelou, E. Faul, J.D. Ford, I. Freimer, N.A. Gao, H. Giegling, I. Gillespie, N.A. Gordon, S.D. Gottesman, R.F. Griswold, M.E. Gudnason, V. Harris, T.B. Hartmann, A.M. Hatzimanolis, A. Heiss, G. Holliday, E.G. Joshi, P.K. Kähönen, M. Kardia, S.L.R. Karlsson, I. Kleineidam, L. Knopman, D.S. Kochan, N.A. Konte, B. Kwok, J.B. Le Hellard, S. Lee, T. Lehtimäki, T. Li, S.-C. Lill, C.M. Liu, T. Koini, M. London, E. Longstreth, W.T., Jr. Lopez, O.L. Loukola, A. Luck, T. Lundervold, A.J. Lundquist, A. Lyytikäinen, L.-P. Martin, N.G. Montgomery, G.W. Murray, A.D. Need, A.C. Noordam, R. Nyberg, L. Ollier, W. Papenberg, G. Pattie, A. Polasek, O. Poldrack, R.A. Psaty, B.M. Reppermund, S. Riedel-Heller, S.G. Rose, R.J. Rotter, J.I. Roussos, P. Rovio, S.P. Saba, Y. Sabb, F.W. Sachdev, P.S. Satizabal, C.L. Schmid, M. Scott, R.J. Scult, M.A. Simino, J. Slagboom, P.E. Smyrnis, N. Soumaré, A. Stefanis, N.C. Stott, D.J. Straub, R.E. Sundet, K. Taylor, A.M. Taylor, K.D. Tzoulaki, I. Tzourio, C. Uitterlinden, A. Vitart, V. Voineskos, A.N. Kaprio, J. Wagner, M. Wagner, H. Weinhold, L. Wen, K.H. Widen, E. Yang, Q. Zhao, W. Adams, H.H.H. Arking, D.E. Bilder, R.M. Bitsios, P. Boerwinkle, E. Chiba-Falek, O. Corvin, A. De Jager, P.L. Debette, S. Donohoe, G. Elliott, P. Fitzpatrick, A.L. Gill, M. Glahn, D.C. Hägg, S. Hansell, N.K. Hariri, A.R. Ikram, M.K. Jukema, J.W. Vuoksimaa, E. Keller, M.C. Kremen, W.S. Launer, L. Lindenberger, U. Palotie, A. Pedersen, N.L. Pendleton, N. Porteous, D.J. Räikkönen, K. Raitakari, O.T. Ramirez, A. Reinvang, I. Rudan, I. Dan Rujescu Schmidt, R. Schmidt, H. Schofield, P.W. Schofield, P.R. Starr, J.M. Steen, V.M. Trollor, J.N. Turner, S.T. Van Duijn, C.M. Villringer, A. Weinberger, D.R. Weir, D.R. Wilson, J.F. Malhotra, A. McIntosh, A.M. Gale, C.R. Seshadri, S. Mosley, T.H., Jr. Bressler, J. Lencz, T. Deary, I.J.

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article. © 2019, The Author(s).

Published
2019

13. Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways

Author

Lam, M. Hill, W.D. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Stahl, E. Huckins, L. Liewald, D.C. Djurovic, S. Melle, I. Sundet, K. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Hartmann, A.M. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Attix, D.K. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Arking, D.E. Smyrnis, N. Bilder, R.M. Freimer, N.A. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Malhotra, A.K. Lencz, T.

Subjects
mental disorders
Abstract

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive (“discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms—early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways—that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness. © 2019

Published
2019

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

Author

Kaufmann, T., Meer, D. van der, Doan, N.T., Schwarz, E., Lund, M.J., Agartz, I., Alnaes, D., Barch, D.M., Baur-Streubel, R., Bertolino, A., Bettella, F., Beyer, M.K., Boen, E., Borgwardt, S., Brandt, C.L., Buitelaar, J.K., Celius, E.G., Cervenka, S., Conzelmann, A., Cordova-Palomera, A., Dale, A.M., de Quervain, D.J.F., Carlo, P. di, Djurovic, S., Dorum, E.S., Eisenacher, S., Elvsashagen, T., Espeseth, T., Fatouros-Bergman, H., Flyckt, L., Franke, B., Frei, O., Haatveit, B., Haberg, A.K., Harbo, H.F., Hartman, C.A, Heslenfeld, D., Hoekstra, P.J., Hogestol, E.A., Jernigan, T.L., Jonassen, R., Jonsson, E.G., Kirsch, P., Kloszewska, I., Kolskar, K.K., Landro, N.I., Hellard, S. Le, Lesch, K.P., Lovestone, S., Lundervold, A., Lundervold, A.J., Maglanoc, L.A., Malt, U.F., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Moberget, T., Norbom, L.B., Nordvik, J.E., Nyberg, L., Oosterlaan, J., Papalino, M., Papassotiropoulos, A., Pauli, P., Pergola, G., Persson, K., Richard, G., Rokicki, J., Sanders, A.M., Selbaek, G., Shadrin, A.A., Smeland, O.B., Soininen, H., Sowa, P., Steen, V.M., Tsolaki, M., Ulrichsen, K.M., Vellas, B., Wang, L, Westman, E., Ziegler, G.C., Zink, M., Andreassen, O.A., Westlye, L.T., Kaufmann, T., Meer, D. van der, Doan, N.T., Schwarz, E., Lund, M.J., Agartz, I., Alnaes, D., Barch, D.M., Baur-Streubel, R., Bertolino, A., Bettella, F., Beyer, M.K., Boen, E., Borgwardt, S., Brandt, C.L., Buitelaar, J.K., Celius, E.G., Cervenka, S., Conzelmann, A., Cordova-Palomera, A., Dale, A.M., de Quervain, D.J.F., Carlo, P. di, Djurovic, S., Dorum, E.S., Eisenacher, S., Elvsashagen, T., Espeseth, T., Fatouros-Bergman, H., Flyckt, L., Franke, B., Frei, O., Haatveit, B., Haberg, A.K., Harbo, H.F., Hartman, C.A, Heslenfeld, D., Hoekstra, P.J., Hogestol, E.A., Jernigan, T.L., Jonassen, R., Jonsson, E.G., Kirsch, P., Kloszewska, I., Kolskar, K.K., Landro, N.I., Hellard, S. Le, Lesch, K.P., Lovestone, S., Lundervold, A., Lundervold, A.J., Maglanoc, L.A., Malt, U.F., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Moberget, T., Norbom, L.B., Nordvik, J.E., Nyberg, L., Oosterlaan, J., Papalino, M., Papassotiropoulos, A., Pauli, P., Pergola, G., Persson, K., Richard, G., Rokicki, J., Sanders, A.M., Selbaek, G., Shadrin, A.A., Smeland, O.B., Soininen, H., Sowa, P., Steen, V.M., Tsolaki, M., Ulrichsen, K.M., Vellas, B., Wang, L, Westman, E., Ziegler, G.C., Zink, M., Andreassen, O.A., and Westlye, L.T.

Abstract

Contains fulltext : 208604.pdf (publisher's version ) (Closed access), Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.

Published
2019

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. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., Deary, I.J., Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Abstract

These authors contributed equally: Gail Davies, Max Lam. These authors jointly supervised this work: Todd Lencz, Ian J. Deary.

Published
2019

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

Author

Sønderby, I.E., Gústafsson, Ó., Doan, N.T., Hibar, D.P., Martin-Brevet, S., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N., Blangero, J., Boomsma, D.I., Bralten, J., Brattbak, H-R, Brodaty, H., Brouwer, R.M., Bülow, R., Calhoun, V., Caspers, S., Cavalleri, G., Chen, C-H, Cichon, S., Ciufolini, S., Corvin, A., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Delanty, N., den Braber, A., Desrivières, S., Donohoe, G., Draganski, B., Ehrlich, S., Espeseth, T., Fisher, S.E., Franke, B., Frouin, V., Fukunaga, M., Gareau, T., Glahn, D.C., Grabe, H., Groenewold, N.A., Haavik, J., Håberg, A., Hashimoto, R., Hehir-Kwa, J.Y., Heinz, A., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Hottenga, J-J, Hulshoff, H.E., Ikeda, M., Jahanshad, N., Jernigan, T., Jockwitz, C., Johansson, S., Jonsdottir, G.A., Jönsson, E.G., Kahn, R., Kaufmann, T., Kelly, S., Kikuchi, M., Knowles, E.E.M., Kolskår, K.K., Kwok, J.B., Hellard, S.L., Leu, C., Liu, J., Lundervold, A.J., Lundervold, A., Martin, N.G., Mather, K., Mathias, S.R., McCormack, M., McMahon, K.L., McRae, A., Milaneschi, Y., Moreau, C., Morris, D., Mothersill, D., Mühleisen, T.W., Murray, R., Nordvik, J.E., Nyberg, L., Olde Loohuis, L.M., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Peralta, J.M., Pike, B., Prieto, C., Pudas, S., Quinlan, E., Quintana, D.S., Reinbold, C.S., Marques, T.R., Reymond, A., Richard, G., Rodriguez-Herreros, B., Roiz-Santiañez, R., Rokicki, J., Rucker, J., Sachdev, P., Sanders, A-M, Sando, S.B., Schmaal, L., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Sisodiya, S., Steen, V.M., Stein, D.J., Steinberg, S., Strike, L., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.S., Ueland, T., Uhlmann, A., Ulfarsson, M.O., van ’t Ent, D., van der Meer, D., van Haren, N.E.M., Vaskinn, A., Vassos, E., Walters, G.B., Wang, Y., Wen, W., Whelan, C.D., Wittfeld, K., Wright, M., Yamamori, H., Zayats, T., Agartz, I., Westlye, L.T., Jacquemont, S., Djurovic, S., Stefánsson, H., Stefánsson, K., Thompson, P., Andreassen, O.A., Sønderby, I.E., Gústafsson, Ó., Doan, N.T., Hibar, D.P., Martin-Brevet, S., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N., Blangero, J., Boomsma, D.I., Bralten, J., Brattbak, H-R, Brodaty, H., Brouwer, R.M., Bülow, R., Calhoun, V., Caspers, S., Cavalleri, G., Chen, C-H, Cichon, S., Ciufolini, S., Corvin, A., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Delanty, N., den Braber, A., Desrivières, S., Donohoe, G., Draganski, B., Ehrlich, S., Espeseth, T., Fisher, S.E., Franke, B., Frouin, V., Fukunaga, M., Gareau, T., Glahn, D.C., Grabe, H., Groenewold, N.A., Haavik, J., Håberg, A., Hashimoto, R., Hehir-Kwa, J.Y., Heinz, A., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Hottenga, J-J, Hulshoff, H.E., Ikeda, M., Jahanshad, N., Jernigan, T., Jockwitz, C., Johansson, S., Jonsdottir, G.A., Jönsson, E.G., Kahn, R., Kaufmann, T., Kelly, S., Kikuchi, M., Knowles, E.E.M., Kolskår, K.K., Kwok, J.B., Hellard, S.L., Leu, C., Liu, J., Lundervold, A.J., Lundervold, A., Martin, N.G., Mather, K., Mathias, S.R., McCormack, M., McMahon, K.L., McRae, A., Milaneschi, Y., Moreau, C., Morris, D., Mothersill, D., Mühleisen, T.W., Murray, R., Nordvik, J.E., Nyberg, L., Olde Loohuis, L.M., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Peralta, J.M., Pike, B., Prieto, C., Pudas, S., Quinlan, E., Quintana, D.S., Reinbold, C.S., Marques, T.R., Reymond, A., Richard, G., Rodriguez-Herreros, B., Roiz-Santiañez, R., Rokicki, J., Rucker, J., Sachdev, P., Sanders, A-M, Sando, S.B., Schmaal, L., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Sisodiya, S., Steen, V.M., Stein, D.J., Steinberg, S., Strike, L., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.S., Ueland, T., Uhlmann, A., Ulfarsson, M.O., van ’t Ent, D., van der Meer, D., van Haren, N.E.M., Vaskinn, A., Vassos, E., Walters, G.B., Wang, Y., Wen, W., Whelan, C.D., Wittfeld, K., Wright, M., Yamamori, H., Zayats, T., Agartz, I., Westlye, L.T., Jacquemont, S., Djurovic, S., Stefánsson, H., Stefánsson, K., Thompson, P., and Andreassen, O.A.

Abstract

Prior to and following the publication of this article the authors noted that the complete list of authors was not included in the main article and was only present in Supplementary Table 1. The author list in the original article has now been updated to include all authors, and Supplementary Table 1 has been removed. All other supplementary files have now been updated accordingly. Furthermore, in Table 1 of this Article, the replication cohort for the row Close relative in data set, n (%) was incorrect. All values have now been corrected to 0(0%). The publishers would like to apologise for this error and the inconvenience it may have caused.

Published
2019

18. The ser9gly SNP in the dopamine D3 receptor causes a shift from cAMP related to PGE2 related signal transduction mechanisms in transfected CHO cells

Author

Hellstrand, M., Danielsen, E.A., Steen, V.M., Ekman, A., Eriksson, E., and Nilsson, C.L.

Subjects
Single nucleotide polymorphisms -- Research, Single nucleotide polymorphisms -- Patient outcomes, Schizophrenia -- Genetic aspects, Movement disorders -- Genetic aspects, Dopamine receptors -- Research, Antipsychotic drugs -- Chemical properties, Health
Published
2004

20. Multi-Trait analysis of gwas and biological insights into cognition: A response to hill (2018)

Author

Lam, M. Trampush, J.W. Yu, J. Knowles, E. Djurovic, S. Melle, I. Sundet, K. Christoforou, A. Reinvang, I. Derosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Attix, D.K. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Arking, D.E. Smyrnis, N. Bilder, R.M. Freimer, N.A. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Hellard, S.L. Keller, M.C. Andreassen, O.A. Glahn, D.C. Malhotra, A.K. Lencz, T.

Abstract

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'. © The Author(s) 2018Â.

Published
2018

21. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author

Savage, J.E. Jansen, P.R. Stringer, S. Watanabe, K. Bryois, J. De Leeuw, C.A. Nagel, M. Awasthi, S. Barr, P.B. Coleman, J.R.I. Grasby, K.L. Hammerschlag, A.R. Kaminski, J.A. Karlsson, R. Krapohl, E. Lam, M. Nygaard, M. Reynolds, C.A. Trampush, J.W. Young, H. Zabaneh, D. Hägg, S. Hansell, N.K. Karlsson, I.K. Linnarsson, S. Montgomery, G.W. Muñoz-Manchado, A.B. Quinlan, E.B. Schumann, G. Skene, N.G. Webb, B.T. White, T. Arking, D.E. Avramopoulos, D. Bilder, R.M. Bitsios, P. Burdick, K.E. Cannon, T.D. Chiba-Falek, O. Christoforou, A. Cirulli, E.T. Congdon, E. Corvin, A. Davies, G. Deary, I.J. Derosse, P. Dickinson, D. Djurovic, S. Donohoe, G. Conley, E.D. Eriksson, J.G. Espeseth, T. Freimer, N.A. Giakoumaki, S. Giegling, I. Gill, M. Glahn, D.C. Hariri, A.R. Hatzimanolis, A. Keller, M.C. Knowles, E. Koltai, D. Konte, B. Lahti, J. Le Hellard, S. Lencz, T. Liewald, D.C. London, E. Lundervold, A.J. Malhotra, A.K. Melle, I. Morris, D. Need, A.C. Ollier, W. Palotie, A. Payton, A. Pendleton, N. Poldrack, R.A. Räikkönen, K. Reinvang, I. Roussos, P. Rujescu, D. Sabb, F.W. Scult, M.A. Smeland, O.B. Smyrnis, N. Starr, J.M. Steen, V.M. Stefanis, N.C. Straub, R.E. Sundet, K. Tiemeier, H. Voineskos, A.N. Weinberger, D.R. Widen, E. Yu, J. Abecasis, G. Andreassen, O.A. Breen, G. Christiansen, L. Debrabant, B. Dick, D.M. Heinz, A. Hjerling-Leffler, J. Ikram, M.A. Kendler, K.S. Martin, N.G. Medland, S.E. Pedersen, N.L. Plomin, R. Polderman, T.J.C. Ripke, S. Van Der Sluis, S. Sullivan, P.F. Vrieze, S.I. Wright, M.J. Posthuma, D.

Abstract

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. © 2018 The Author(s).

Published
2018

22. Analysis of shared heritability in common disorders of the brain

Author

Anttila, V. Bulik-Sullivan, B. Finucane, H.K. Walters, R.K. Bras, J. Duncan, L. Escott-Price, V. Falcone, G.J. Gormley, P. Malik, R. Patsopoulos, N.A. Ripke, S. Wei, Z. Yu, D. Lee, P.H. Turley, P. Grenier-Boley, B. Chouraki, V. Kamatani, Y. Berr, C. Letenneur, L. Hannequin, D. Amouyel, P. Boland, A. Deleuze, J.-F. Duron, E. Vardarajan, B.N. Reitz, C. Goate, A.M. Huentelman, M.J. Ilyas Kamboh, M. Larson, E.B. Rogaeva, E. George-Hyslop, P.S. Hakonarson, H. Kukull, W.A. Farrer, L.A. Barnes, L.L. Beach, T.G. Yesim Demirci, F. Head, E. Hulette, C.M. Jicha, G.A. Kauwe, J.S.K. Kaye, J.A. Leverenz, J.B. Levey, A.I. Lieberman, A.P. Pankratz, V.S. Poon, W.W. Quinn, J.F. Saykin, A.J. Schneider, L.S. Smith, A.G. Sonnen, J.A. Stern, R.A. Van Deerlin, V.M. Van Eldik, L.J. Harold, D. Russo, G. Rubinsztein, D.C. Bayer, A. Tsolaki, M. Proitsi, P. Fox, N.C. Hampel, H. Owen, M.J. Mead, S. Passmore, P. Morgan, K. Nöthen, M.M. Rossor, M. Lupton, M.K. Hoffmann, P. Kornhuber, J. Lawlor, B. McQuillin, A. Al-Chalabi, A. Bis, J.C. Ruiz, A. Boada, M. Seshadri, S. Beiser, A. Rice, K. Van Der Lee, S.J. De Jager, P.L. Geschwind, D.H. Riemenschneider, M. Riedel-Heller, S. Rotter, J.I. Ransmayr, G. Hyman, B.T. Cruchaga, C. Alegret, M. Winsvold, B. Palta, P. Farh, K.-H. Cuenca-Leon, E. Furlotte, N. Kurth, T. Ligthart, L. Terwindt, G.M. Freilinger, T. Ran, C. Gordon, S.D. Borck, G. Adams, H.H.H. Lehtimäki, T. Wedenoja, J. Buring, J.E. Schürks, M. Hrafnsdottir, M. Hottenga, J.-J. Penninx, B. Artto, V. Kaunisto, M. Vepsäläinen, S. Martin, N.G. Montgomery, G.W. Kurki, M.I. Hämäläinen, E. Huang, H. Huang, J. Sandor, C. Webber, C. Muller-Myhsok, B. Schreiber, S. Salomaa, V. Loehrer, E. Göbel, H. Macaya, A. Pozo-Rosich, P. Hansen, T. Werge, T. Kaprio, J. Metspalu, A. Kubisch, C. Ferrari, M.D. Belin, A.C. Van Den Maagdenberg, A.M.J.M. Zwart, J.-A. Boomsma, D. Eriksson, N. Olesen, J. Chasman, D.I. Nyholt, D.R. Avbersek, A. Baum, L. Berkovic, S. Bradfield, J. Buono, R. Catarino, C.B. Cossette, P. De Jonghe, P. Depondt, C. Dlugos, D. Ferraro, T.N. French, J. Hjalgrim, H. Jamnadas-Khoda, J. Kälviäinen, R. Kunz, W.S. Lerche, H. Leu, C. Lindhout, D. Lo, W. Lowenstein, D. McCormack, M. Møller, R.S. Molloy, A. Ng, P.-W. Oliver, K. Privitera, M. Radtke, R. Ruppert, A.-K. Sander, T. Schachter, S. Schankin, C. Scheffer, I. Schoch, S. Sisodiya, S.M. Smith, P. Sperling, M. Striano, P. Surges, R. Neil Thomas, G. Visscher, F. Whelan, C.D. Zara, F. Heinzen, E.L. Marson, A. Becker, F. Stroink, H. Zimprich, F. Gasser, T. Gibbs, R. Heutink, P. Martinez, M. Morris, H.R. Sharma, M. Ryten, M. Mok, K.Y. Pulit, S. Bevan, S. Holliday, E. Attia, J. Battey, T. Boncoraglio, G. Thijs, V. Chen, W.-M. Mitchell, B. Rothwell, P. Sharma, P. Sudlow, C. Vicente, A. Markus, H. Kourkoulis, C. Pera, J. Raffeld, M. Silliman, S. Perica, V.B. Thornton, L.M. Huckins, L.M. William Rayner, N. Lewis, C.M. Gratacos, M. Rybakowski, F. Keski-Rahkonen, A. Raevuori, A. Hudson, J.I. Reichborn-Kjennerud, T. Monteleone, P. Karwautz, A. Mannik, K. Baker, J.H. O'Toole, J.K. Trace, S.E. Davis, O.S.P. Helder, S.G. Ehrlich, S. Herpertz-Dahlmann, B. Danner, U.N. Van Elburg, A.A. Clementi, M. Forzan, M. Docampo, E. Lissowska, J. Hauser, J. Tortorella, A. Maj, M. Gonidakis, F. Tziouvas, K. Papezova, H. Yilmaz, Z. Wagner, G. Cohen-Woods, S. Herms, S. Julia, A. Rabionet, R. Dick, D.M. Ripatti, S. Andreassen, O.A. Espeseth, T. Lundervold, A.J. Steen, V.M. Pinto, D. Scherer, S.W. Aschauer, H. Schosser, A. Alfredsson, L. Padyukov, L. Halmi, K.A. Mitchell, J. Strober, M. Bergen, A.W. Kaye, W. Szatkiewicz, J.P. Cormand, B. Ramos-Quiroga, J.A. Sánchez-Mora, C. Ribasés, M. Casas, M. Hervas, A. Arranz, M.J. Haavik, J. Zayats, T. Johansson, S. Williams, N. Dempfle, A. Rothenberger, A. Kuntsi, J. Oades, R.D. Banaschewski, T. Franke, B. Buitelaar, J.K. Vasquez, A.A. Doyle, A.E. Reif, A. Lesch, K.-P. Freitag, C. Rivero, O. Palmason, H. Romanos, M. Langley, K. Rietschel, M. Witt, S.H. Dalsgaard, S. Børglum, A.D. Waldman, I. Wilmot, B. Molly, N. Bau, C.H.D. Crosbie, J. Schachar, R. Loo, S.K. McGough, J.J. Grevet, E.H. Medland, S.E. Robinson, E. Weiss, L.A. Bacchelli, E. Bailey, A. Bal, V. Battaglia, A. Betancur, C. Bolton, P. Cantor, R. Celestino-Soper, P. Dawson, G. De Rubeis, S. Duque, F. Green, A. Klauck, S.M. Leboyer, M. Levitt, P. Maestrini, E. Mane, S. Moreno-De-Luca, D. Parr, J. Regan, R. Reichenberg, A. Sandin, S. Vorstman, J. Wassink, T. Wijsman, E. Cook, E. Santangelo, S. Delorme, R. Roge, B. Magalhaes, T. Arking, D. Schulze, T.G. Thompson, R.C. Strohmaier, J. Matthews, K. Melle, I. Morris, D. Blackwood, D. McIntosh, A. Bergen, S.E. Schalling, M. Jamain, S. Maaser, A. Fischer, S.B. Reinbold, C.S. Fullerton, J.M. Guzman-Parra, J. Mayoral, F. Schofield, P.R. Cichon, S. Mühleisen, T.W. Degenhardt, F. Schumacher, J. Bauer, M. Mitchell, P.B. Gershon, E.S. Rice, J. Potash, J.B. Zandi, P.P. Craddock, N. Nicol Ferrier, I. Alda, M. Rouleau, G.A. Turecki, G. Ophoff, R. Pato, C. Anjorin, A. Stahl, E. Leber, M. Czerski, P.M. Cruceanu, C. Jones, I.R. Posthuma, D. Andlauer, T.F.M. Forstner, A.J. Streit, F. Baune, B.T. Air, T. Sinnamon, G. Wray, N.R. MacIntyre, D.J. Porteous, D. Homuth, G. Rivera, M. Grove, J. Middeldorp, C.M. Hickie, I. Pergadia, M. Mehta, D. Smit, J.H. Jansen, R. De Geus, E. Dunn, E. Li, Q.S. Nauck, M. Schoevers, R.A. Beekman, A.T.F. Knowles, J.A. Viktorin, A. Arnold, P. Barr, C.L. Bedoya-Berrio, G. Joseph Bienvenu, O. Brentani, H. Burton, C. Camarena, B. Cappi, C. Cath, D. Cavallini, M. Cusi, D. Darrow, S. Denys, D. Derks, E.M. Dietrich, A. Fernandez, T. Figee, M. Freimer, N. Gerber, G. Grados, M. Greenberg, E. Hanna, G.L. Hartmann, A. Hirschtritt, M.E. Hoekstra, P.J. Huang, A. Huyser, C. Illmann, C. Jenike, M. Kuperman, S. Leventhal, B. Lochner, C. Lyon, G.J. Macciardi, F. Madruga-Garrido, M. Malaty, I.A. Maras, A. McGrath, L. Miguel, E.C. Mir, P. Nestadt, G. Nicolini, H. Okun, M.S. Pakstis, A. Paschou, P. Piacentini, J. Pittenger, C. Plessen, K. Ramensky, V. Ramos, E.M. Reus, V. Richter, M.A. Riddle, M.A. Robertson, M.M. Roessner, V. Rosário, M. Samuels, J.F. Sandor, P. Stein, D.J. Tsetsos, F. Van Nieuwerburgh, F. Weatherall, S. Wendland, J.R. Wolanczyk, T. Worbe, Y. Zai, G. Goes, F.S. McLaughlin, N. Nestadt, P.S. Grabe, H.-J. Depienne, C. Konkashbaev, A. Lanzagorta, N. Valencia-Duarte, A. Bramon, E. Buccola, N. Cahn, W. Cairns, M. Chong, S.A. Cohen, D. Crespo-Facorro, B. Crowley, J. Davidson, M. DeLisi, L. Dinan, T. Donohoe, G. Drapeau, E. Duan, J. Haan, L. Hougaard, D. Karachanak-Yankova, S. Khrunin, A. Klovins, J. Kučinskas, V. Keong, J.L.C. Limborska, S. Loughland, C. Lönnqvist, J. Maher, B. Mattheisen, M. McDonald, C. Murphy, K.C. Nenadic, I. Van Os, J. Pantelis, C. Pato, M. Petryshen, T. Quested, D. Roussos, P. Sanders, A.R. Schall, U. Schwab, S.G. Sim, K. So, H.-C. Stögmann, E. Subramaniam, M. Toncheva, D. Waddington, J. Walters, J. Weiser, M. Cheng, W. Cloninger, R. Curtis, D. Gejman, P.V. Henskens, F. Mattingsdal, M. Oh, S.-Y. Scott, R. Webb, B. Breen, G. Churchhouse, C. Bulik, C.M. Daly, M. Dichgans, M. Faraone, S.V. Guerreiro, R. Holmans, P. Kendler, K.S. Koeleman, B. Mathews, C.A. Price, A. Scharf, J. Sklar, P. Williams, J. Wood, N.W. Cotsapas, C. Palotie, A. Smoller, J.W. Sullivan, P. Rosand, J. Corvin, A. Neale, B.M. The Brainstorm Consortium

Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.

Published
2018

23. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), Deary, I.J. (Ian), Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), and Deary, I.J. (Ian)

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the c

Published
2018
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24. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C, Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., Deary, I.J., Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C, Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16–102) and find 148 genome-wide significant independent loci (P < 5 × 10−8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Published
2018

25. Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets

Author

Lam, M. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Liewald, D.C. Starr, J.M. Djurovic, S. Melle, I. Sundet, K. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Attix, D.K. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Arking, D.E. Smyrnis, N. Bilder, R.M. Freimer, N.A. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Malhotra, A.K. Lencz, T.

Abstract

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability (“g”), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth. Lam et al. conduct a large-scale genome-wide association study of cognitive ability, identifying 70 associated loci. Results provide biological insights into the molecular basis of individual differences in cognitive ability, as well as their relationship to psychiatric and other health-relevant phenotypes. © 2017 The Author(s)

Published
2017

26. A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

Author

Li, D. Chang, X. Connolly, J.J. Tian, L. Liu, Y. Bhoj, E.J. Robinson, N. Abrams, D. Li, Y.R. Bradfield, J.P. Kim, C.E. Li, J. Wang, F. Snyder, J. Lemma, M. Hou, C. Wei, Z. Guo, Y. Qiu, H. Mentch, F.D. Thomas, K.A. Chiavacci, R.M. Cone, R. Li, B. Sleiman, P.A. Hakonarson, H. Perica, V.B. Franklin, C.S. Floyd, J.A.B. Thornton, L.M. Huckins, L.M. Southam, L. Rayner, N.W. Tachmazidou, I. Schmidt, U. Tozzi, F. Kiezebrink, K. Hebebrand, J. Gorwood, P. Adan, R.A.H. Kas, M.J.H. Favaro, A. Santonastaso, P. Fernánde-Aranda, F. Gratacos, M. Rybakowski, F. Dmitrzak-Weglarz, M. Kaprio, J. Keski-Rahkonen, A. Raevuori-Helkamaa, A. Furth, E.F.V. Slof-Opt Landt, M.C.T. Hudson, J.I. Reichborn-Kjennerud, T. Knudsen, G.P.S. Monteleone, P. Karwautz, A. Berrettini, W.H. Schork, N.J. Ando, T. Inoko, H. Esko, T. Fischer, K. Männik, K. Metspalu, A. Baker, J.H. DeSocio, J.E. Hilliard, C.E. O'Toole, J.K. Pantel, J. Szatkiewicz, J.P. Zerwas, S. Davis, O.S.P. Helder, S. Bühren, K. Burghardt, R. De Zwaan, M. Egberts, K. Ehrlich, S. Herpertz-Dahlmann, B. Herzog, W. Imgart, H. Scherag, A. Zipfel, S. Boni, C. Ramoz, N. Versini, A. Danner, U.N. Hendriks, J. Koeleman, B.P.C. Ophoff, R.A. Strengman, E. Van Elburg, A.A. Bruson, A. Clementi, M. Degortes, D. Forzan, M. Tenconi, E. Docampo, E. Escaramís, G. Jiménez-Murcia, S. Lissowska, J. Rajewski, A. Szeszenia-Dabrowska, N. Slopien, A. Hauser, J. Karhunen, L. Meulenbelt, I. Slagboom, P.E. Tortorella, A. Maj, M. Dedoussis, G. DIkeos, D. Gonidakis, F. Tziouvas, K. Tsitsika, A. Papezova, H. Slachtova, L. Martaskova, D. Kennedy, J.L. Levitan, R.D. Yilmaz, Z. Huemer, J. Koubek, D. Merl, E. Wagner, G. Lichtenstein, P. Breen, G. Cohen-Woods, S. Farmer, A. McGuffin, P. Cichon, S. Giegling, I. Herms, S. Rujescu, D. Schreiber, S. Wichmann, H.-E. DIna, C. Sladek, R. Gambaro, G. Soranzo, N. Julia, A. Marsal, S. Rabionet, R. Gaborieau, V. DIck, D.M. Palotie, A. Ripatti, S. Widén, E. Andreassen, O.A. Espeseth, T. Lundervold, A. Reinvang, I. Steen, V.M. Le Hellard, S. Mattingsdal, M. Ntalla, I. Bencko, V. Foretova, L. Janout, V. Navratilova, M. Gallinger, S. Pinto, D. Scherer, S.W. Aschauer, H. Carlberg, L. Schosser, A. Alfredsson, L. DIng, B. Klareskog, L. Padyukov, L. Finan, C. Kalsi, G. Roberts, M. Barrett, J.C. Estivill, X. Hinney, A. Sullivan, P.F. Zeggini, E. Bulik, C.M. Brandt, H. Crawford, S. Crow, S. Fichter, M.M. Halmi, K.A. Johnson, C. Kaplan, A.S. La Via, M.C. Mitchell, J. Strober, M. Rotondo, A. Treasure, J. Woodside, D.B. Keel, P.K. Klump, K.L. Lilenfeld, L. Bergen, A.W. Kaye, W. Magistretti, P.

Abstract

We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation. © 2017 The Author(s).

Published
2017

27. BRCA Testing by Single-Molecule Molecular Inversion Probes

Author

Neveling, K., Mensenkamp, A.R., Derks, R, Kwint, M.P., Ouchene, H., Steehouwer, M., Lier, L.A. van, Bosgoed, E.A.J., Rikken, A., Tychon, M.W.J., Zafeiropoulou, D., Castelein, S., Hehir-Kwa, J.Y., Thung, G.W., Hofste, T., Lelieveld, S.H., Bertens, S.M., Adan, I.B., Eijkelenboom, A., Tops, B.B.J., Yntema, H.G., Stokowy, T., Knappskog, P.M., Hoberg-Vetti, H., Steen, V.M., Boyle, E., Martin, B., Ligtenberg, M.J.L., Shendure, J., Nelen, M.R., Hoischen, A., Neveling, K., Mensenkamp, A.R., Derks, R, Kwint, M.P., Ouchene, H., Steehouwer, M., Lier, L.A. van, Bosgoed, E.A.J., Rikken, A., Tychon, M.W.J., Zafeiropoulou, D., Castelein, S., Hehir-Kwa, J.Y., Thung, G.W., Hofste, T., Lelieveld, S.H., Bertens, S.M., Adan, I.B., Eijkelenboom, A., Tops, B.B.J., Yntema, H.G., Stokowy, T., Knappskog, P.M., Hoberg-Vetti, H., Steen, V.M., Boyle, E., Martin, B., Ligtenberg, M.J.L., Shendure, J., Nelen, M.R., and Hoischen, A.

Abstract

Contains fulltext : 169902.pdf (publisher's version ) (Closed access), BACKGROUND: Despite advances in next generation DNA sequencing (NGS), NGS-based single gene tests for diagnostic purposes require improvements in terms of completeness, quality, speed, and cost. Single-molecule molecular inversion probes (smMIPs) are a technology with unrealized potential in the area of clinical genetic testing. In this proof-of-concept study, we selected 2 frequently requested gene tests, those for the breast cancer genes BRCA1 and BRCA2, and developed an automated work flow based on smMIPs. METHODS: The BRCA1 and BRCA2 smMIPs were validated using 166 human genomic DNA samples with known variant status. A generic automated work flow was built to perform smMIP-based enrichment and sequencing for BRCA1, BRCA2, and the checkpoint kinase 2 (CHEK2) c.1100del variant. RESULTS: Pathogenic and benign variants were analyzed in a subset of 152 previously BRCA-genotyped samples, yielding an analytical sensitivity and specificity of 100%. Following automation, blind analysis of 65 in-house samples and 267 Norwegian samples correctly identified all true-positive variants (>3000), with no false positives. Consequent to process optimization, turnaround times were reduced by 60% to currently 10-15 days. Copy number variants were detected with an analytical sensitivity of 100% and an analytical specificity of 88%. CONCLUSIONS: smMIP-based genetic testing enables automated and reliable analysis of the coding sequences of BRCA1 and BRCA2. The use of single-molecule tags, double-tiled targeted enrichment, and capturing and sequencing in duplo, in combination with automated library preparation and data analysis, results in a robust process and reduces routine turnaround times. Furthermore, smMIP-based copy number variation analysis could make independent copy number variation tools like multiplex ligation-dependent probes amplification dispensable.

Published
2017

28. Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families

Author

Ngcungcu, T., Oti, M.O., Sitek, J.C., Haukanes, B.I., Linghu, B., Bruccoleri, R., Stokowy, T., Oakeley, E.J., Yang, F, Zhu, J., Sultan, M., Schalkwijk, J., Vlijmen-Willems, I.M.J.J. van, Lippe, C., Brunner, H.G., Ersland, K.M., Grayson, W., Buechmann-Moller, S., Sundnes, O., Nirmala, N., Morgan, T.M., Bokhoven, H. van, Steen, V.M., Hull, P.R., Szustakowski, J., Staedtler, F., Zhou, H., Fiskerstrand, T., Ramsay, M., Ngcungcu, T., Oti, M.O., Sitek, J.C., Haukanes, B.I., Linghu, B., Bruccoleri, R., Stokowy, T., Oakeley, E.J., Yang, F, Zhu, J., Sultan, M., Schalkwijk, J., Vlijmen-Willems, I.M.J.J. van, Lippe, C., Brunner, H.G., Ersland, K.M., Grayson, W., Buechmann-Moller, S., Sundnes, O., Nirmala, N., Morgan, T.M., Bokhoven, H. van, Steen, V.M., Hull, P.R., Szustakowski, J., Staedtler, F., Zhou, H., Fiskerstrand, T., and Ramsay, M.

Abstract

Contains fulltext : 174194.pdf (publisher's version ) (Closed access), Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals.

Published
2017

29. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Author

Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), Montgomery, G.W. (G. W.), Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. 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(Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), and Montgomery, G.W. (G. W.)

Abstract

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the associa

Published
2017
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30. 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
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31. 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

32. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Author

Davies, G., Armstrong, N., Bis, J.C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C.A., Kirin, M., Lahti, J., Lee, S.J. van der, Hellard, S. le, Liu, T., Marioni, R.E., Oldmeadow, C., Postmus, I., Smith, A.V., Smith, J.A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S.E., Hill, W.D., Liewald, D.C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A.A., Au, R., Becker, J.T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B.M., Campbell, H., Corley, J., Jager, P.L. de, Dufouil, C., Eriksson, J.G., Espeseth, T., Faul, J.D., Ford, I., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Heiss, G., Hofman, A., Holliday, E.G., Huffman, J., Kardia, S.L.R., Kochan, N., Knopman, D.S., Kwok, J.B., Lambert, J.C., Lee, T., Li, G., Li, S.C., Loitfelder, M., Lopez, O.L., Lundervold, A.J., Lundqvist, A., Mather, K.A., Mirza, S.S., Nyberg, L., Oostra, B.A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B.M., Redmond, P., Reppermund, S., Rotter, J.I., Schmidt, H., Schuur, M., Schofield, P.W., Scott, R.J., Steen, V.M., Stott, D.J., Swieten, J.C. van, Taylor, K.D., Trollor, J., Trompet, S., Uitterlinden, A.G., Weinstein, G., Widen, E., Windham, B.G., Jukema, J.W., Wright, A.F., Wright, M.J., Yang, Q., Amieva, H., Attia, J.R., Bennett, D.A., Brodaty, H., Craen, A.J.M. de, Hayward, C., Ikram, M.A., Lindenberger, U., Nilsson, L.G., Porteous, D.J., Raikkonen, K., Reinvang, I., Rudan, I., Sachdev, P.S., Schmidt, R., Schofield, P.R., Srikanth, V., Starr, J.M., Turner, S.T., Weir, D.R., Wilson, J.F., Duijn, C. van, Launer, L., Fitzpatrick, A.L., Seshadri, S., Jr, T.H.M., Deary, I.J., and Generation Scotland

Subjects
Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 [VDP], Social sciences: 200::Psychology: 260::Cognitive psychology: 267 [VDP], Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714 [VDP], Samfunnsvitenskap: 200::Psykologi: 260::Kognitiv psykologi: 267 [VDP]
Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer’s disease: TOMM40, APOE, ABCG1 and MEF2C. publishedVersion

Published
2015

33. 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

34. BRCA1/2 testing in newly diagnosed breast and ovarian cancer patients without prior genetic counselling: the DNA-BONus study

Author

Hoberg-Vetti, H., Bjorvatn, C., Fiane, B.E., Aas, T., Woie, K., Espelid, H., Rusken, T., Eikesdal, H.P., Listol, W., Haavind, M.T., Knappskog, P.M., Haukanes, B.I., Steen, V.M., Hoogerbrugge, N., Hoberg-Vetti, H., Bjorvatn, C., Fiane, B.E., Aas, T., Woie, K., Espelid, H., Rusken, T., Eikesdal, H.P., Listol, W., Haavind, M.T., Knappskog, P.M., Haukanes, B.I., Steen, V.M., and Hoogerbrugge, N.

Abstract

Contains fulltext : 172006.pdf (publisher's version ) (Open Access), Germline BRCA1/2 testing of breast and ovarian cancer patients is growing rapidly as the result affects both treatment and cancer prevention in patients and relatives. Through the DNA-BONus study we offered BRCA1/2 testing and familial risk assessment to all new patients with breast (N=893) or ovarian (N=122) cancer diagnosed between September 2012 and April 2015, irrespective of family history or age, and without prior face-to-face genetic counselling. BRCA1/2 testing was accepted by 405 (45.4%) and 83 (68.0%) of the patients with breast or ovarian cancer, respectively. A pathogenic BRCA1/2 variant was found in 7 (1.7%) of the breast cancer patients and 19 (22.3%) of the ovarian cancer patients. In retrospect, all BRCA1/2 mutation carriers appeared to fulfill current criteria for BRCA1/2 testing. Hospital Anxiety and Depression Scale (HADS) scores showed that the mean levels of anxiety and depression were comparable to those reported for breast and gynecological cancer patients in general, with a significant drop in anxiety symptoms during a 6-month follow-up period, during which the test result was forwarded to the patients. These results show that BRCA1/2 testing is well accepted in newly diagnosed breast and ovarian cancer patients. Current test criteria based on age and family history are sufficient to identify most BRCA1/2 mutation carriers among breast cancer patients. We recommend germline BRCA1/2 testing in all patients with epithelial ovarian cancer because of the high prevalence of pathogenic BRCA1/2 variants.

Published
2016

35. RareVariantVis: new tool for visualization of causative variants in rare monogenic disorders using whole genome sequencing data

Author

Stokowy, T., Garbulowski, M., Fiskerstrand, T., Holdhus, R., Labun, K., Sztromwasser, P., Gilissen, C., Hoischen, A., Houge, G., Petersen, K., Jonassen, I., Steen, V.M., Stokowy, T., Garbulowski, M., Fiskerstrand, T., Holdhus, R., Labun, K., Sztromwasser, P., Gilissen, C., Hoischen, A., Houge, G., Petersen, K., Jonassen, I., and Steen, V.M.

Abstract

Item does not contain fulltext, MOTIVATION: The search for causative genetic variants in rare diseases of presumed monogenic inheritance has been boosted by the implementation of whole exome (WES) and whole genome (WGS) sequencing. In many cases, WGS seems to be superior to WES, but the analysis and visualization of the vast amounts of data is demanding. RESULTS: To aid this challenge, we have developed a new tool-RareVariantVis-for analysis of genome sequence data (including non-coding regions) for both germ line and somatic variants. It visualizes variants along their respective chromosomes, providing information about exact chromosomal position, zygosity and frequency, with point-and-click information regarding dbSNP IDs, gene association and variant inheritance. Rare variants as well as de novo variants can be flagged in different colors. We show the performance of the RareVariantVis tool in the Genome in a Bottle WGS data set. AVAILABILITY AND IMPLEMENTATION: https://www.bioconductor.org/packages/3.3/bioc/html/RareVariantVis.html CONTACT: tomasz.stokowy@k2.uib.no SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Published
2016

36. A genome-wide association study of anorexia nervosa

Author

Boraska, V. Franklin, C.S. Floyd, J.A.B. Thornton, L.M. Huckins, L.M. Southam, L. Rayner, N.W. Tachmazidou, I. Klump, K.L. Treasure, J. Lewis, C.M. Schmidt, U. Tozzi, F. Kiezebrink, K. Hebebrand, J. Gorwood, P. Adan, R.A.H. Kas, M.J.H. Favaro, A. Santonastaso, P. Fernández-Aranda, F. Gratacos, M. Rybakowski, F. Dmitrzak-Weglarz, M. Kaprio, J. Keski-Rahkonen, A. Raevuori, A. Van Furth, E.F. Slof-Op 't Landt, M.C.T. Hudson, J.I. Reichborn-Kjennerud, T. Knudsen, G.P.S. Monteleone, P. Kaplan, A.S. Karwautz, A. Hakonarson, H. Berrettini, W.H. Guo, Y. Li, D. Schork, N.J. Komaki, G. Ando, T. Inoko, H. Esko, T. Fischer, K. Männik, K. Metspalu, A. Baker, J.H. Cone, R.D. Dackor, J. DeSocio, J.E. Hilliard, C.E. O'Toole, J.K. Pantel, J. Szatkiewicz, J.P. Taico, C. Zerwas, S. Trace, S.E. Davis, O.S.P. Helder, S. Bühren, K. Burghardt, R. De Zwaan, M. Egberts, K. Ehrlich, S. Herpertz-Dahlmann, B. Herzog, W. Imgart, H. Scherag, A. Scherag, S. Zipfel, S. Boni, C. Ramoz, N. Versini, A. Brandys, M.K. Danner, U.N. De Kovel, C. Hendriks, J. Koeleman, B.P.C. Ophoff, R.A. Strengman, E. Van Elburg, A.A. Bruson, A. Clementi, M. Degortes, D. Forzan, M. Tenconi, E. Docampo, E. Escaramís, G. Jiménez-Murcia, S. Lissowska, J. Rajewski, A. Szeszenia-Dabrowska, N. Slopien, A. Hauser, J. Karhunen, L. Meulenbelt, I. Slagboom, P.E. Tortorella, A. Maj, M. Dedoussis, G. Dikeos, D. Gonidakis, F. Tziouvas, K. Tsitsika, A. Papezova, H. Slachtova, L. Martaskova, D. Kennedy, J.L. Levitan, R.D. Yilmaz, Z. Huemer, J. Koubek, D. Merl, E. Wagner, G. Lichtenstein, P. Breen, G. Cohen-Woods, S. Farmer, A. McGuffin, P. Cichon, S. Giegling, I. Herms, S. Rujescu, D. Schreiber, S. Wichmann, H.-E. Dina, C. Sladek, R. Gambaro, G. Soranzo, N. Julia, A. Marsal, S. Rabionet, R. Gaborieau, V. Dick, D.M. Palotie, A. Ripatti, S. Widén, E. Andreassen, O.A. Espeseth, T. Lundervold, A. Reinvang, I. Steen, V.M. Le Hellard, S. Mattingsdal, M. Ntalla, I. Bencko, V. Foretova, L. Janout, V. Navratilova, M. Gallinger, S. Pinto, D. Scherer, S.W. Aschauer, H. Carlberg, L. Schosser, A. Alfredsson, L. Ding, B. Klareskog, L. Padyukov, L. Courtet, P. Guillaume, S. Jaussent, I. Finan, C. Kalsi, G. Roberts, M. Logan, D.W. Peltonen, L. Ritchie, G.R.S. Barrett, J.C. Anderson, C.A. McGinnis, R. Zeggini, E. Sambrook, J. Stephens, J. Ouwehand, W.H. McArdle, W.L. Ring, S.M. Strachan, D.P. Alexander, G. Bulik, C.M. Collier, D.A. Conlon, P.J. Dominiczak, A. Duncanson, A. Hill, A. Langford, C. Lord, G. Maxwell, A.P. Morgan, L. Sandford, R.N. Sheerin, N. Vannberg, F.O. Blackburn, H. Chen, W.-M. Edkins, S. Gillman, M. Gray, E. Hunt, S.E. Onengut-Gumuscu, S. Potter, S. Rich, S.S. Simpkin, D. Whittaker, P. Estivill, X. Hinney, A. Sullivan, P.F. The Wellcome Trust Case Control Consortium 3

Abstract

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 × 10-7) in SOX2OT and rs17030795 (P = 5.84 × 10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 × 10-6) between CUL3 and FAM124B and rs1886797 (P = 8.05 × 10-6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P = 4 × 10-6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. © 2014 Macmillan Publishers Limited All rights reserved.

Published
2014

37. Using ancestry-informative markers to identify fine structure across 15 populations of European origin

Author

Huckins, L.M. Boraska, V. Franklin, C.S. Floyd, J.A.B. Southam, L. Sullivan, P.F. Bulik, C.M. Collier, D.A. Tyler-Smith, C. Zeggini, E. Tachmazidou, I. Thornton, L.M. William Rayner, N. Klump, K.L. Treasure, J. Schmidt, U. Tozzi, F. Kiezebrink, K. Hebebrand, J. Gorwood, P. Adan, R.A.H. Kas, M.J.H. Favaro, A. Santonastaso, P. Fernández-Aranda, F. Gratacos, M. Rybakowski, F. Dmitrzak-Weglarz, M. Kaprio, J. Keski-Rahkonen, A. Raevuori, A. Van Furth, E.F. Slof-Op t Landt, M.C.T. Hudson, J.I. Reichborn-Kjennerud, T. Knudsen, G.P.S. Monteleone, P. Kaplan, A.S. Karwautz, A. Hakonarson, H. Berrettini, W.H. Guo, Y. Li, D. Schork, N.J. Komaki, G. Ando, T. Inoko, H. Esko, T. Fischer, K. Männik, K. Metspalu, A. Baker, J.H. Cone, R.D. Dackor, J. DeSocio, J.E. Hilliard, C.E. O'Toole, J.K. Pantel, J. Szatkiewicz, J.P. Taico, C. Zerwas, S. Trace, S.E. Davis, O.S.P. Helder, S. Bühren, K. Burghardt, R. de Zwaan, M. Egberts, K. Ehrlich, S. Herpertz-Dahlmann, B. Herzog, W. Imgart, H. Scherag, S. Zipfel, S. Boni, C. Ramoz, N. Versini, A. Brandys, M.K. Danner, U.N. de Kovel, C. Hendriks, J. Koeleman, B.P.C. Ophoff, R.A. Strengman, E. van Elburg, A.A. Bruson, A. Clementi, M. Degortes, D. Forzan, M. Tenconi, E. Docampo, E. Escaramís, G. Jiménez-Murcia, S. Lissowska, J. Rajewski, A. Szeszenia-Dabrowska, N. Slopien, A. Hauser, J. Karhunen, L. Meulenbelt, I. Slagboom, P.E. Tortorella, A. Maj, M. Dedoussis, G. Dikeos, D. Gonidakis, F. Tziouvas, K. Tsitsika, A. Papezova, H. Slachtova, L. Martaskova, D. Kennedy, J.L. Levitan, R.D. Yilmaz, Z. Huemer, J. Koubek, D. Merl, E. Wagner, G. Lichtenstein, P. Breen, G. Cohen-Woods, S. Farmer, A. McGuffin, P. Cichon, S. Giegling, I. Herms, S. Rujescu, D. Schreiber, S. Wichmann, H.-E. Dina, C. Sladek, R. Gambaro, G. Soranzo, N. Julia, A. Marsal, S. Rabionet, R. Gaborieau, V. Dick, D.M. Palotie, A. Ripatti, S. Widén, E. Andreassen, O.A. Espeseth, T. Lundervold, A. Reinvang, I. Steen, V.M. Le Hellard, S. Mattingsdal, M. Ntalla, I. Bencko, V. Foretova, L. Janout, V. Navratilova, M. Gallinger, S. Pinto, D. Scherer, S.W. Aschauer, H. Carlberg, L. Schosser, A. Alfredsson, L. Ding, B. Klareskog, L. Padyukov, L. Finan, C. Kalsi, G. Roberts, M. Logan, D.W. Peltonen, L. Ritchie, G.R.S. Courtet, P. Guillame, S. Jaussent, I. Barrett, J.C. Estivill, X. Hinney, A. Bulik, C.M. McGinnis, R. Sambrook, J. Stephens, J. Ouwehand, W.H. McArdle, W.L. Ring, S.M. Strachan, D.P. Alexander, G. Conlon, P.J. Dominiczak, A. Anderson, C.A. Hill, A. Langford, C. Lord, G. Maxwell, A.P. Morgan, L. Sandford, R.N. Sheerin, N. Vannberg, F.O. Blackburn, H. Chen, W.-M. Edkins, S. Gillman, M. Gray, E. Hunt, S.E. Onengut-Gumuscu, S. Potter, S. Rich, S.S. Simpkin, D. Whittaker, P.

Abstract

The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia. © 2014 Macmillan Publishers Limited All rights reserved.

Published
2014

38. B56delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability

Author

Houge, G., Haesen, D., Vissers, L.E.L.M., Mehta, S., Parker, M.J., Wright, M., Vogt, J., McKee, S., Tolmie, J.L., Cordeiro, N., Kleefstra, T., Willemsen, M.H., Reijnders, M.R.F., Berland, S., Hayman, E., Lahat, E., Brilstra, E.H., Gassen, K.L. van, Zonneveld-Huijssoon, E., Bie, C.I. De, Hoischen, A., Eichler, E.E., Holdhus, R., Steen, V.M., Doskeland, S.O., Hurles, M.E., FitzPatrick, D.R., Janssens, V., Houge, G., Haesen, D., Vissers, L.E.L.M., Mehta, S., Parker, M.J., Wright, M., Vogt, J., McKee, S., Tolmie, J.L., Cordeiro, N., Kleefstra, T., Willemsen, M.H., Reijnders, M.R.F., Berland, S., Hayman, E., Lahat, E., Brilstra, E.H., Gassen, K.L. van, Zonneveld-Huijssoon, E., Bie, C.I. De, Hoischen, A., Eichler, E.E., Holdhus, R., Steen, V.M., Doskeland, S.O., Hurles, M.E., FitzPatrick, D.R., and Janssens, V.

Abstract

Contains fulltext : 154618.pdf (publisher's version ) (Open Access), Here we report inherited dysregulation of protein phosphatase activity as a cause of intellectual disability (ID). De novo missense mutations in 2 subunits of serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) were identified in 16 individuals with mild to severe ID, long-lasting hypotonia, epileptic susceptibility, frontal bossing, mild hypertelorism, and downslanting palpebral fissures. PP2A comprises catalytic (C), scaffolding (A), and regulatory (B) subunits that determine subcellular anchoring, substrate specificity, and physiological function. Ten patients had mutations within a highly conserved acidic loop of the PPP2R5D-encoded B56delta regulatory subunit, with the same E198K mutation present in 6 individuals. Five patients had mutations in the PPP2R1A-encoded scaffolding Aalpha subunit, with the same R182W mutation in 3 individuals. Some Aalpha cases presented with large ventricles, causing macrocephaly and hydrocephalus suspicion, and all cases exhibited partial or complete corpus callosum agenesis. Functional evaluation revealed that mutant A and B subunits were stable and uncoupled from phosphatase activity. Mutant B56delta was A and C binding-deficient, while mutant Aalpha subunits bound B56delta well but were unable to bind C or bound a catalytically impaired C, suggesting a dominant-negative effect where mutant subunits hinder dephosphorylation of B56delta-anchored substrates. Moreover, mutant subunit overexpression resulted in hyperphosphorylation of GSK3beta, a B56delta-regulated substrate. This effect was in line with clinical observations, supporting a correlation between the ID degree and biochemical disturbance.

Published
2015

39. Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium

Author

Davies, G. (Gail), Armstrong, N.J. (Nicola), Bis, J.C. (Joshua), Bressler, J. (Jan), Chouraki, V. (Vincent), Giddaluru, S. (Sudheer), Hofer, E., Ibrahim-Verbaas, C.A. (Carla), Kirin, M. (Mirna), Lahti, J., Lee, S.J. (Sven) van der, Le Hellard, S. (Stephanie), Liu, T., Marioni, R.E. (Riccardo), Oldmeadow, C. (Christopher), Postmus, D. (Douwe), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Thalamuthu, A. (Anbupalam), Thomson, R. (Russell), Vitart, V. (Veronique), Wang, J., Yu, L., Zgaga, L. (Lina), Zhao, W. (Wei), Boxall, R. (Ruth), Harris, S.E. (Sarah), Hill, W.D. (W. David), Liewald, D.C. (David C.), Luciano, M. (Michelle), Adams, H.H.H. (Hieab), Ames, D. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Assareh, A.A., Au, R., Becker, J.T. (James), Beiser, A., Berr, C. (Claudine), Bertram, L. (Lars), Boerwinkle, E.A. (Eric), Buckley, B.M. (Brendan M.), Campbell, H. (Harry), Corley, J. (Janie), De Jager, P.L., Dufouil, C. (Carole), Eriksson, J.G. (Johan G.), Espeseth, T. (Thomas), Faul, J.D., Ford, I., Scotland, G. (Generation), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B., Heiss, G. (Gerardo), Hofman, A. (Albert), Holliday, E.G. (Elizabeth), Huffman, J.E. (Jennifer), Kardia, S.L.R. (Sharon), Kochan, N.A. (Nicole A.), Knopman, D.S. (David), Kwok, J.B., Lambert, J.-C., Lee, T., Li, G., Li, S.-C., Loitfelder, M. (Marisa), Lopez, O.L. (Oscar), Lundervold, A.J., Lundqvist, A., Mather, R., Mirza, S.S. (Saira), Nyberg, L., Oostra, B.A. (Ben), Palotie, A. (Aarno), Papenberg, G., Pattie, A. (Alison), Petrovic, K. (Katja), Polasek, O. (Ozren), Psaty, B.M. (Bruce), Redmond, P. (Paul), Reppermund, S., Rotter, J.I., Schmidt, R. (Reinhold), Schuur, M. (Maaike), Schofield, P.W., Scott, R.J., Steen, V.M. (Vidar), Stott, D.J. (David J.), Swieten, J.C. (John) van, Taylor, K.D. (Kent), Trollor, J., Trompet, S. (Stella), Uitterlinden, A.G. (André), Weinstein, G., Widen, E. (Elisabeth), Windham, B.G. (Gwen), Jukema, J.W. (Jan Wouter), Wright, A. (Alan), Wright, M.J. (Margaret), Yang, Q. (Qiong Fang), Amieva, H. (Hélène), Attia, J. (John), Bennett, D.A. (David), Brodaty, H. (Henry), Craen, A.J. (Anton) de, Hayward, C., Ikram, M.A. (Arfan), Lindenberger, U., Nilsson, L.-G., Porteous, D.J. (David J.), Räikkönen, K. (Katri), Reinvang, I. (Ivar), Rudan, I. (Igor), Sachdev, P.S. (Perminder), Schmidt, R., Schofield, P. (Peter), Srikanth, V., Starr, J.M. (John), Turner, S.T. (Stephen), Weir, D.R. (David R.), Wilson, J.F. (James F), Duijn, C.M. (Cornelia) van, Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Deary, I.J. (Ian), Davies, G. (Gail), Armstrong, N.J. (Nicola), Bis, J.C. (Joshua), Bressler, J. (Jan), Chouraki, V. (Vincent), Giddaluru, S. (Sudheer), Hofer, E., Ibrahim-Verbaas, C.A. (Carla), Kirin, M. (Mirna), Lahti, J., Lee, S.J. (Sven) van der, Le Hellard, S. (Stephanie), Liu, T., Marioni, R.E. (Riccardo), Oldmeadow, C. (Christopher), Postmus, D. (Douwe), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Thalamuthu, A. (Anbupalam), Thomson, R. (Russell), Vitart, V. (Veronique), Wang, J., Yu, L., Zgaga, L. (Lina), Zhao, W. (Wei), Boxall, R. (Ruth), Harris, S.E. (Sarah), Hill, W.D. (W. David), Liewald, D.C. (David C.), Luciano, M. (Michelle), Adams, H.H.H. (Hieab), Ames, D. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Assareh, A.A., Au, R., Becker, J.T. (James), Beiser, A., Berr, C. (Claudine), Bertram, L. (Lars), Boerwinkle, E.A. (Eric), Buckley, B.M. (Brendan M.), Campbell, H. (Harry), Corley, J. (Janie), De Jager, P.L., Dufouil, C. (Carole), Eriksson, J.G. (Johan G.), Espeseth, T. (Thomas), Faul, J.D., Ford, I., Scotland, G. (Generation), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B., Heiss, G. (Gerardo), Hofman, A. (Albert), Holliday, E.G. (Elizabeth), Huffman, J.E. (Jennifer), Kardia, S.L.R. (Sharon), Kochan, N.A. (Nicole A.), Knopman, D.S. (David), Kwok, J.B., Lambert, J.-C., Lee, T., Li, G., Li, S.-C., Loitfelder, M. (Marisa), Lopez, O.L. (Oscar), Lundervold, A.J., Lundqvist, A., Mather, R., Mirza, S.S. (Saira), Nyberg, L., Oostra, B.A. (Ben), Palotie, A. (Aarno), Papenberg, G., Pattie, A. (Alison), Petrovic, K. (Katja), Polasek, O. (Ozren), Psaty, B.M. (Bruce), Redmond, P. (Paul), Reppermund, S., Rotter, J.I., Schmidt, R. (Reinhold), Schuur, M. (Maaike), Schofield, P.W., Scott, R.J., Steen, V.M. (Vidar), Stott, D.J. (David J.), Swieten, J.C. (John) van, Taylor, K.D. (Kent), Trollor, J., Trompet, S. (Stella), Uitterlinden, A.G. (André), Weinstein, G., Widen, E. (Elisabeth), Windham, B.G. (Gwen), Jukema, J.W. (Jan Wouter), Wright, A. (Alan), Wright, M.J. (Margaret), Yang, Q. (Qiong Fang), Amieva, H. (Hélène), Attia, J. (John), Bennett, D.A. (David), Brodaty, H. (Henry), Craen, A.J. (Anton) de, Hayward, C., Ikram, M.A. (Arfan), Lindenberger, U., Nilsson, L.-G., Porteous, D.J. (David J.), Räikkönen, K. (Katri), Reinvang, I. (Ivar), Rudan, I. (Igor), Sachdev, P.S. (Perminder), Schmidt, R., Schofield, P. (Peter), Srikanth, V., Starr, J.M. (John), Turner, S.T. (Stephen), Weir, D.R. (David R.), Wilson, J.F. (James F), Duijn, C.M. (Cornelia) van, Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), and Deary, I.J. (Ian)

Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10-9, MIR2113; rs17522122, P=2.55 × 10-8, AKAP6; rs10119, P=5.67 × 10-9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10-6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ∼1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10-17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Published
2015
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40. 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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41. 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

42. Syndromic X-linked intellectual disability segregating with a missense variant in RLIM

Author

Tonne, E., Holdhus, R., Stansberg, C., Stray-Pedersen, A., Petersen, K., Brunner, H.G., Gilissen, C., Hoischen, A., Prescott, T., Steen, V.M., Fiskerstrand, T., Tonne, E., Holdhus, R., Stansberg, C., Stray-Pedersen, A., Petersen, K., Brunner, H.G., Gilissen, C., Hoischen, A., Prescott, T., Steen, V.M., and Fiskerstrand, T.

Abstract

Item does not contain fulltext, We describe a three-generation Norwegian family with a novel X-linked intellectual disability (XLID) syndrome characterized by subtle facial dysmorphism, autism and severe feeding problems. By exome sequencing we detected a rare missense variant (c.1067A>G, p.(Tyr356Cys)) in the RLIM gene, in two affected male second cousins. Sanger sequencing confirmed the presence of the variant in the four affected males (none of whom were siblings) and in three mothers available for testing. The variant was not present in 100 normal Norwegian controls, has not been reported in variant databases and is deleterious according to in silico prediction tools. The clinical phenotype and the variant co-segregate, yielding a LOD score of 3.0 for linkage to the shared region (36.09 Mb), which contains 242 genes. No other shared rare variants on the X chromosome were detected in the two affected exome-sequenced individuals, and all female carriers had an extremely skewed X-chromosome inactivation pattern. RLIM encodes RING zinc finger protein 12 (RNF12), an ubiquitin ligase that is essential for X inactivation in mice and that acts as a co-regulator of a range of transcription factors, particularly those containing a LIM homeodomain. Tyrosine in position 356 in RNF12 is located within a highly conserved domain essential for binding such transcription factors. Expression of RNF12 is widespread during embryogenesis, and is particularly high in the outer layers of the cerebral cortex. Functional studies are needed to prove a definite causal relationship between the variant and the phenotype. Subsequent reports may confirm a role for RLIM variants in patients with XLID.

Published
2015

44. 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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45. 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., Vasquez, A.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., 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., de Geus, E.J., den Braber, A., Delvecchio, G., Depondt, C., de Haan, L., de Zubicaray, G.I., 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., 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., Grabe, H.J., Grimm, O., Gruber, O., Guadalupe, T., Gur, R.E., Gur, R.C., Goring, H.H., Hagenaars, S., Hajek, T., Hall, G.B., Hall, J., Hardy, J., Hartman, C.A., Hass, J., Hatton, S.N., Haukvik, U.K., Hegenscheid, K., Heinz, A., Hickie, I.B., Ho, B.C., Hoehn, D., Hoekstra, P.J., Hollinshead, M., Holmes, A.J., Homuth, G., Hoogman, M., Hong, L.E., Hosten, N., Hottenga, J.J., Hulshoff Pol, H.E., Hwang, K.S., Jack, C.R., Jenkinson, M., Johnston, C., Jonsson, E.G., Kahn, R.S., Kasperaviciute, D., Kelly, S., Kim, S., Kochunov, P., Koenders, L., Kramer, B., Kwok, J.B., Lagopoulos, J., Laje, G., Landen, M., Landman, B.A., Lauriello, J., Lawrie, S.M., Lee, P.H., Le Hellard, S., Lemaitre, H., Leonardo, C.D., Li, C.S., Liberg, B., Liewald, D.C., Liu, X., Lopez, L.M., Loth, E., Lourdusamy, A., Luciano, M., Macciardi, F., Machielsen, M.W., Macqueen, G.M., Malt, U.F., Mandl, R., Manoach, D.S., Martinot, J.L., Matarin, M., Mather, K.A., Mattheisen, M., Mattingsdal, M., Meyer-Lindenberg, A., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Meisenzahl, E., Melle, I., Milaneschi, Y., Mohnke, S., Montgomery, G.W., Morris, D.W., Moses, E.K., Mueller, B.A., Munoz Maniega, S., Muhleisen, T.W., Muller-Myhsok, B., Mwangi, B., Nauck, M., Nho, K., Nichols, T.E., Nilsson, L.G., Nugent, A.C., Nyberg, L., Olvera, R.L., Oosterlaan, J., Ophoff, R.A., Pandolfo, M., Papalampropoulou-Tsiridou, M., Papmeyer, M., Paus, T., Pausova, Z., Pearlson, G.D., Penninx, B.W., Peterson, C.P., Pfennig, A., Phillips, M., Pike, G.B., Poline, J.B., Potkin, S.G., Putz, B., Ramasamy, A., Rasmussen, J., Rietschel, M., Rijpkema, M., Risacher, S.L., Roffman, J.L., Roiz-Santianez, R., Romanczuk-Seiferth, N., Rose, E.J., Royle, N.A., Rujescu, D., Ryten, M., Sachdev, P.S., Salami, A., Satterthwaite, T.D., Savitz, J., Saykin, A.J., Scanlon, C., Schmaal, L., Schnack, H.G., Schork, A.J., Schulz, S.C., Schur, R., Seidman, L., Shen, L., Shoemaker, J.M., Simmons, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soares, J.C., Sponheim, S.R., Sprooten, E., Starr, J.M., Steen, V.M., Strakowski, S., Strike, L., Sussmann, J., Samann, P.G., Teumer, A., Toga, A.W., Tordesillas-Gutierrez, D., Trabzuni, D., Trost, S., Turner, J., Van den Heuvel, M., van der Wee, N.J., van Eijk, K., van Erp, T.G., van Haren, N.E., van 't Ent, D., van Tol, M.J., Valdes Hernandez, M.C., Veltman, D.J., Versace, A., Volzke, H., Walker, R., Walter, H., Wang, L., Wardlaw, J.M., Weale, M.E., Weiner, M.W., Wen, W., Westlye, L.T., Whalley, H.C., Whelan, C.D., White, T., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Zilles, D., Zwiers, M.P., Thalamuthu, A., Schofield, P.R., Freimer, N.B., Lawrence, N.S., Drevets, W., Thompson, P.M., Stein, J.L., Medland, S.E., Hibar, D.P., Vasquez, A.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., 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., de Geus, E.J., den Braber, A., Delvecchio, G., Depondt, C., de Haan, L., de Zubicaray, G.I., 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., 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., Grabe, H.J., Grimm, O., Gruber, O., Guadalupe, T., Gur, R.E., Gur, R.C., Goring, H.H., Hagenaars, S., Hajek, T., Hall, G.B., Hall, J., Hardy, J., Hartman, C.A., Hass, J., Hatton, S.N., Haukvik, U.K., Hegenscheid, K., Heinz, A., Hickie, I.B., Ho, B.C., Hoehn, D., Hoekstra, P.J., Hollinshead, M., Holmes, A.J., Homuth, G., Hoogman, M., Hong, L.E., Hosten, N., Hottenga, J.J., Hulshoff Pol, H.E., Hwang, K.S., Jack, C.R., Jenkinson, M., Johnston, C., Jonsson, E.G., Kahn, R.S., Kasperaviciute, D., Kelly, S., Kim, S., Kochunov, P., Koenders, L., Kramer, B., Kwok, J.B., Lagopoulos, J., Laje, G., Landen, M., Landman, B.A., Lauriello, J., Lawrie, S.M., Lee, P.H., Le Hellard, S., Lemaitre, H., Leonardo, C.D., Li, C.S., Liberg, B., Liewald, D.C., Liu, X., Lopez, L.M., Loth, E., Lourdusamy, A., Luciano, M., Macciardi, F., Machielsen, M.W., Macqueen, G.M., Malt, U.F., Mandl, R., Manoach, D.S., Martinot, J.L., Matarin, M., Mather, K.A., Mattheisen, M., Mattingsdal, M., Meyer-Lindenberg, A., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Meisenzahl, E., Melle, I., Milaneschi, Y., Mohnke, S., Montgomery, G.W., Morris, D.W., Moses, E.K., Mueller, B.A., Munoz Maniega, S., Muhleisen, T.W., Muller-Myhsok, B., Mwangi, B., Nauck, M., Nho, K., Nichols, T.E., Nilsson, L.G., Nugent, A.C., Nyberg, L., Olvera, R.L., Oosterlaan, J., Ophoff, R.A., Pandolfo, M., Papalampropoulou-Tsiridou, M., Papmeyer, M., Paus, T., Pausova, Z., Pearlson, G.D., Penninx, B.W., Peterson, C.P., Pfennig, A., Phillips, M., Pike, G.B., Poline, J.B., Potkin, S.G., Putz, B., Ramasamy, A., Rasmussen, J., Rietschel, M., Rijpkema, M., Risacher, S.L., Roffman, J.L., Roiz-Santianez, R., Romanczuk-Seiferth, N., Rose, E.J., Royle, N.A., Rujescu, D., Ryten, M., Sachdev, P.S., Salami, A., Satterthwaite, T.D., Savitz, J., Saykin, A.J., Scanlon, C., Schmaal, L., Schnack, H.G., Schork, A.J., Schulz, S.C., Schur, R., Seidman, L., Shen, L., Shoemaker, J.M., Simmons, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soares, J.C., Sponheim, S.R., Sprooten, E., Starr, J.M., Steen, V.M., Strakowski, S., Strike, L., Sussmann, J., Samann, P.G., Teumer, A., Toga, A.W., Tordesillas-Gutierrez, D., Trabzuni, D., Trost, S., Turner, J., Van den Heuvel, M., van der Wee, N.J., van Eijk, K., van Erp, T.G., van Haren, N.E., van 't Ent, D., van Tol, M.J., Valdes Hernandez, M.C., Veltman, D.J., Versace, A., Volzke, H., Walker, R., Walter, H., Wang, L., Wardlaw, J.M., Weale, M.E., Weiner, M.W., Wen, W., Westlye, L.T., Whalley, H.C., Whelan, C.D., White, T., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Zilles, D., Zwiers, M.P., Thalamuthu, A., Schofield, P.R., Freimer, N.B., Lawrence, N.S., 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.

Published
2014

46. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis

Author

Coste, B., Houge, G., Murray, M.F., Stitziel, N., Bandell, M., Giovanni, M.A., Philippakis, A., Hoischen, A., Riemer, G., Steen, U., Steen, V.M., Mathur, J., Cox, J., Lebo, M., Rehm, H., Weiss, S.T., Wood, J.N., Maas, R.L., Sunyaev, S.R., Patapoutian, A., Coste, B., Houge, G., Murray, M.F., Stitziel, N., Bandell, M., Giovanni, M.A., Philippakis, A., Hoischen, A., Riemer, G., Steen, U., Steen, V.M., Mathur, J., Cox, J., Lebo, M., Rehm, H., Weiss, S.T., Wood, J.N., Maas, R.L., Sunyaev, S.R., and Patapoutian, A.

Abstract

Item does not contain fulltext

Published
2013

47. A genetic deconstruction of neurocognitive traits in schizophrenia and bipolar disorder

Author

Fernandes, C.P.D. (Carla P.), Christoforou, A. (Andrea), Giddaluru, S. (Sudheer), Ersland, K.M. (Kari), Djurovic, S. (Srdjan), Mattheisen, M. (Manuel), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Nöthen, M.M. (Markus), Rietschel, M. (Marcella), Ophoff, R.A. (Roel), Hofman, A. (Albert), Uitterlinden, A.G. (André), Werge, T.M. (Thomas), Cichon, S. (Sven), Espeseth, T. (Thomas), Andreassen, O.A. (Ole), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Fernandes, C.P.D. (Carla P.), Christoforou, A. (Andrea), Giddaluru, S. (Sudheer), Ersland, K.M. (Kari), Djurovic, S. (Srdjan), Mattheisen, M. (Manuel), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Nöthen, M.M. (Markus), Rietschel, M. (Marcella), Ophoff, R.A. (Roel), Hofman, A. (Albert), Uitterlinden, A.G. (André), Werge, T.M. (Thomas), Cichon, S. (Sven), Espeseth, T. (Thomas), Andreassen, O.A. (Ole), Steen, V.M. (Vidar), and Le Hellard, S. (Stephanie)

Abstract

Background: Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders. Methods: Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS) on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests. These gene sets were then tested for enrichment of association in GWASs of schizophrenia and bipolar disorder. The GWAS data was derived from three independent single-centre schizophrenia samples, three independent single-centre bipolar disorder samples, and the multi-centre schizophrenia and bipolar disorder samples from the Psychiatric Genomics Consortium. Results: The strongest enrichments were observed for visuospatial attention and verbal abilities sets in bipolar disorder. Delayed verbal memory was also enriched in one sample of bipolar disorder. For schizophrenia, the strongest evidence of enrichment was observed for the sets of genes associated with performance in a colour-word interference test and for sets associated with memory learning slope. Conclusions: Our results are consistent with the increasing evidence that cognitive functions share genetic factors with schizophrenia and bipolar disorder. Our data provides evidence that genetic studies using polygenic and pleiotropic models can be used to link specific cognitive functions with psychiatric disorders.

Published
2013
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48. 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

49. Association Analysis of Schizophrenia on 18 Genes Involved in Neuronal Migration: MDGA1 as a New Susceptibility Gene

Author

Kahler, A.K., Djurovic, S., Kulle, B., Jonsson, E.G., Agartz, I., Hall, H., Opjordsmoen, S., Jakobsen, K.D., Hansen, T., Melle, I., Werge, T., Steen, V.M., Andreassen, O.A., Kahler, A.K., Djurovic, S., Kulle, B., Jonsson, E.G., Agartz, I., Hall, H., Opjordsmoen, S., Jakobsen, K.D., Hansen, T., Melle, I., Werge, T., Steen, V.M., and Andreassen, O.A.

Abstract

Udgivelsesdato: 2008

Published
2008

50. O.21 Genetic characterisation of PHARC – a novel syndrome resembling Refsum’s disease

Author

Bindoff, L.A., primary, Fiskerstrand, T., additional, Brahim, D. H’mida-Ben, additional, Johansson, S., additional, M’zahem, A., additional, Haukanes, B.I., additional, Drouot, N., additional, Zimmermann, J., additional, Cole, A.J., additional, Vedeler, C., additional, Bredrup, C., additional, Assoum, M., additional, Tazir, M., additional, Klockgether, T., additional, Hamri, A., additional, Steen, V.M., additional, Boman, H., additional, Koenig, M., additional, and Knappskog, P.M., additional

Published
2010
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