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568 results on '"Burmeister, M."'

1. The hot and the cool otbursts in the symbiotic system AG Draconis

Author

Cikała, M., Mikołajewski, M., Osiwała, J., Tomov, T., Leedjarv, L., and Burmeister, M.

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

In this papper we present the analyses of the six (1998, 1997, 2001, 2002, 2003 and 2005) last outbursts of AG Draconis on the basis of low resolution visual spectroscopy. A new method to determine the Zanstra's temperature of the hot ionizing source from the optical Hb and HeII emission lines has been used. As a results we obtained the evolution of the individual outburst on the H-R diagram.

Published
2011

2. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Author

Culverhouse, R C, Saccone, N L, Horton, A C, Ma, Y, Anstey, K J, Banaschewski, T, Burmeister, M, Cohen-Woods, S, Etain, B, Fisher, H L, Goldman, N, Guillaume, S, Horwood, J, Juhasz, G, Lester, K J, Mandelli, L, Middeldorp, C M, Olié, E, Villafuerte, S, Air, T M, Araya, R, Bowes, L, Burns, R, Byrne, E M, Coffey, C, Coventry, W L, Gawronski, K AB, Glei, D, Hatzimanolis, A, Hottenga, J-J, Jaussent, I, Jawahar, C, Jennen-Steinmetz, C, Kramer, J R, Lajnef, M, Little, K, zu Schwabedissen, H M, Nauck, M, Nederhof, E, Petschner, P, Peyrot, W J, Schwahn, C, Sinnamon, G, Stacey, D, Tian, Y, Toben, C, Van der Auwera, S, Wainwright, N, Wang, J-C, Willemsen, G, Anderson, I M, Arolt, V, Åslund, C, Bagdy, G, Baune, B T, Bellivier, F, Boomsma, D I, Courtet, P, Dannlowski, U, de Geus, E JC, Deakin, J FW, Easteal, S, Eley, T, Fergusson, D M, Goate, A M, Gonda, X, Grabe, H J, Holzman, C, Johnson, E O, Kennedy, M, Laucht, M, Martin, N G, Munafò, M R, Nilsson, K W, Oldehinkel, A J, Olsson, C A, Ormel, J, Otte, C, Patton, G C, Penninx, B WJH, Ritchie, K, Sarchiapone, M, Scheid, J M, Serretti, A, Smit, J H, Stefanis, N C, Surtees, P G, Völzke, H, Weinstein, M, Whooley, M, Nurnberger, J I, Jr, Breslau, N, and Bierut, L J

Published
2018
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4. News from AG Draconis

Author

Leedjärv L. and Burmeister M.

Subjects
stars, symbiotic, individual (ag dra), spectroscopy, emission lines, Astronomy, QB1-991
Abstract

AG Dra is a classical symbiotic star that undergoes major outbursts at intervals between 12-15 years. We present spectroscopic observations of four emission lines (Hα, Hβ, He II 4686 Å, Raman scattered OVI 6825 Å) before, during and after the major outburst that started in 2006. Interesting strengthenings of the emission lines took place in late 2005 and in early 2008. the latter was followed by a very deep minimum in the line strengths in 2008–2009.

Published
2012
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5. Fast 3D imaging of giant unilamellar vesicles using re ected light-sheet microscopy with single molecule sensitivity

Author

Jannasch, A., Szilagyi, S.A., Burmeister, M., Davis, Q.T., Hermsdorf, G.L., De, S., and Schäffer, E.

Abstract

Observation of highly dynamic processes inside living cells at the single molecule level is key for a better understanding of biological systems. However, imaging of single molecules in living cells is usually limited by the spatial and temporal resolution, photobleaching and the signal-to-background ratio. To overcome these limitations, light-sheet microscopes with thin selective plane illumination, for example, in a reflected geometry with a high numerical aperture imaging objective, have been developed. Here, we developed a reflected light-sheet microscope with active optics for fast, high contrast, two-colour acquisition of urn:x-wiley:00222720:media:jmi13070:jmi13070-math-0001-stacks. We demonstrate fast volume scanning by imaging a two-colour giant unilamellar vesicle (GUV) hemisphere. In addition, the high contrast enabled the imaging and tracking of single lipids in the GUV cap. The enhanced reflected scanning light-sheet microscope enables fast 3D scanning of artificial membrane systems and potentially live cells with single-molecule sensitivity and thereby could provide quantitative and molecular insight into the operation of cells.

Published
2021

6. The genetic architecture of depression in samples with East Asian ancestry

Author

Giannakopoulou, O., Lin, K., Meng, X., Su, M., Kuo, P., Peterson, R., Awasthi, S., Moscati, A., Coleman, J., Bass, N., Millwood, I., Chen, Y., Chen, Z., Li, L., Chen, H., Lu, M., Huang, M., Chen, C., Stahl, E., Loos, R., Mullins, N., Ursano, R., Kessler, R., Stein, M., Sen, S., Scott, L., Burmeister, M., Fang, Y., Tyrrell, J., Jiang, Y., Tian, C., McIntosh, A., Ripke, S., Dunn, E., Kendler, K., Walters, R., Lewis, C., Kuchenbaecker, K., Research Team, T, and Major Depressive Disorder Working Group of the PGC, T

Subjects
RC0321, BF, RC
Abstract

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European (EUR) descent. This limits our understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.\ud Objectives: to investigate the genetics of depression across East Asian and European cultural contexts and outcome definitions.\ud Design: Genome-wide association studies, followed by meta-analysis. \ud Setting: Nine cohort and case-control studies from China, Taiwan, USA and UK. \ud Participants: 15,771 depression cases and 178,777 controls of East Asian descent (EAS). \ud Exposures: Associations of genetic variants with depression risk were assessed using generalised linear mixed models and logistic regression. The results were combined across studies using fixed effects meta-analyses. These were subsequently also meta-analysed with the largest published GWAS for depression in EUR samples. Additional meta-analyses were carried out separately by outcome definition (clinical vs symptom-based) and region (East Asian countries vs Western countries). \ud Main outcomes and measures: Depression status was defined based on health records and self-report questionnaires.\ud Results: In total we identified five novel associations, including one in the EAS meta-analysis for broad depression: rs4656484 (beta=-0.018, SE=0.003, P=4.43x10-8) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (P=5.03x10-9). Both associations were specific to EAS samples (P=0.53 and P=0.28 in EUR, respectively). Only 11% of depression loci previously identified in EUR reached nominal significance levels in the EAS samples. The trans-ancestry genetic correlation estimates with depression in EUR ranged from 0.223 to 0.558, depending on the outcome definition. Clinical depression risk was negatively genetically correlated with BMI in EAS (rg=-0.212), contrary to findings from EUR samples.\ud Conclusions and relevance: Our results suggest that cultural differences further add to the heterogeneity of depression and thereby impact on the genetic architecture. This cautions against generalising findings about depression risk factors across populations and highlights the need to increase the ancestral and geographic diversity of samples with consistent phenotyping.

Published
2021

8. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Author

Andlauer, TFM, Guzman-Parra, J, Streit, F, Strohmaier, J, González, MJ, Gil Flores, S, Cabaleiro Fabeiro, FJ, del Río Noriega, F, Perez, FP, Haro González, J, Orozco Diaz, G, de Diego-Otero, Y, Moreno-Küstner, B, Auburger, G, Degenhardt, F, Heilmann-Heimbach, S, Herms, S, Hoffmann, P, Frank, J, Foo, JC, Treutlein, J, Witt, SH, Cichon, S, Kogevinas, M, Stahl, EA, Breen, G, Forstner, AJ, McQuillin, A, Ripke, S, Trubetskoy, V, Mattheisen, M, Wang, Y, Coleman, JRI, Gaspar, HA, de Leeuw, CA, Steinberg, S, Pavlides, JMW, Trzaskowski, M, Pers, TH, Holmans, PA, Abbott, L, Agerbo, E, Akil, H, Albani, D, Alliey-Rodriguez, N, Als, TD, Anjorin, A, Antilla, V, Awasthi, S, Badner, JA, Bækvad-Hansen, M, Barchas, JD, Bass, N, Bauer, M, Belliveau, R, Bergen, SE, Pedersen, CB, Bøen, E, Boks, M, Boocock, J, Budde, M, Bunney, W, Burmeister, M, Bybjerg-Grauholm, J, Byerley, W, Casas, M, Cerrato, F, Cervantes, P, Chambert, K, Charney, AW, Chen, D, Churchhouse, C, Clarke, TK, Coryell, W, Craig, DW, Cruceanu, C, Czerski, PM, Dale, AM, de Jong, S, Del-Favero, J, DePaulo, JR, Djurovic, S, Dobbyn, AL, Dumont, A, Elvsåshagen, T, Escott-Price, V, Fan, CC, Fischer, SB, Flickinger, M, Foroud, TM, Forty, L, Fraser, C, Freimer, NB, Frisén, L, Gade, K, Gage, D, Garnham, J, Giambartolomei, C, Andlauer, TFM, Guzman-Parra, J, Streit, F, Strohmaier, J, González, MJ, Gil Flores, S, Cabaleiro Fabeiro, FJ, del Río Noriega, F, Perez, FP, Haro González, J, Orozco Diaz, G, de Diego-Otero, Y, Moreno-Küstner, B, Auburger, G, Degenhardt, F, Heilmann-Heimbach, S, Herms, S, Hoffmann, P, Frank, J, Foo, JC, Treutlein, J, Witt, SH, Cichon, S, Kogevinas, M, Stahl, EA, Breen, G, Forstner, AJ, McQuillin, A, Ripke, S, Trubetskoy, V, Mattheisen, M, Wang, Y, Coleman, JRI, Gaspar, HA, de Leeuw, CA, Steinberg, S, Pavlides, JMW, Trzaskowski, M, Pers, TH, Holmans, PA, Abbott, L, Agerbo, E, Akil, H, Albani, D, Alliey-Rodriguez, N, Als, TD, Anjorin, A, Antilla, V, Awasthi, S, Badner, JA, Bækvad-Hansen, M, Barchas, JD, Bass, N, Bauer, M, Belliveau, R, Bergen, SE, Pedersen, CB, Bøen, E, Boks, M, Boocock, J, Budde, M, Bunney, W, Burmeister, M, Bybjerg-Grauholm, J, Byerley, W, Casas, M, Cerrato, F, Cervantes, P, Chambert, K, Charney, AW, Chen, D, Churchhouse, C, Clarke, TK, Coryell, W, Craig, DW, Cruceanu, C, Czerski, PM, Dale, AM, de Jong, S, Del-Favero, J, DePaulo, JR, Djurovic, S, Dobbyn, AL, Dumont, A, Elvsåshagen, T, Escott-Price, V, Fan, CC, Fischer, SB, Flickinger, M, Foroud, TM, Forty, L, Fraser, C, Freimer, NB, Frisén, L, Gade, K, Gage, D, Garnham, J, and Giambartolomei, C

Abstract

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

Published
2021

12. A second cohort of CHD3 patients expands the molecular mechanisms known to cause Snijders Blok-Campeau syndrome

Author

Drivas, T. G., Li, D., Nair, D., Alaimo, J. T., Alders, M., Altmuller, J., Barakat, T. S., Bebin, E. M., Bertsch, N. L., Blackburn, P. R., Blesson, A., Bouman, A. M., Brockmann, K., Brunelle, P., Burmeister, M., Cooper, G. M., Denecke, J., Dieux-Coeslier, A., Dubbs, H., Ferrer, A., Gal, D., Bartik, L. E., Gunderson, L. B., Hasadsri, L., Jain, M., Karimov, C., Keena, B., Klee, E. W., Kloth, K., Lace, B., Macchiaiolo, M., Marcadier, J. L., Milunsky, J. M., Napier, M. P., Ortiz-Gonzalez, X. R., Pichurin, P. N., Pinner, J., Powis, Z., Prasad, C., Radio, F. C., Rasmussen, K. J., Renaud, D. L., Rush, E. T., Saunders, C., Selcen, D., Seman, A. R., Shinde, D. N., Smith, E. D., Smol, T., Snijders Blok, L., Stoler, J. M., Tang, S., Tartaglia, M., Thompson, M. L., van de Kamp, J. M., Wang, J., Weise, D., Weiss, K., Woitschach, R., Wollnik, B., Yan, H., Zackai, E. H., Zampino, Giuseppe, Campeau, P., Bhoj, E., Zampino G. (ORCID:0000-0003-3865-3253), Drivas, T. G., Li, D., Nair, D., Alaimo, J. T., Alders, M., Altmuller, J., Barakat, T. S., Bebin, E. M., Bertsch, N. L., Blackburn, P. R., Blesson, A., Bouman, A. M., Brockmann, K., Brunelle, P., Burmeister, M., Cooper, G. M., Denecke, J., Dieux-Coeslier, A., Dubbs, H., Ferrer, A., Gal, D., Bartik, L. E., Gunderson, L. B., Hasadsri, L., Jain, M., Karimov, C., Keena, B., Klee, E. W., Kloth, K., Lace, B., Macchiaiolo, M., Marcadier, J. L., Milunsky, J. M., Napier, M. P., Ortiz-Gonzalez, X. R., Pichurin, P. N., Pinner, J., Powis, Z., Prasad, C., Radio, F. C., Rasmussen, K. J., Renaud, D. L., Rush, E. T., Saunders, C., Selcen, D., Seman, A. R., Shinde, D. N., Smith, E. D., Smol, T., Snijders Blok, L., Stoler, J. M., Tang, S., Tartaglia, M., Thompson, M. L., van de Kamp, J. M., Wang, J., Weise, D., Weiss, K., Woitschach, R., Wollnik, B., Yan, H., Zackai, E. H., Zampino, Giuseppe, Campeau, P., Bhoj, E., and Zampino G. (ORCID:0000-0003-3865-3253)

Abstract

There has been one previous report of a cohort of patients with variants in Chromodomain Helicase DNA-binding 3 (CHD3), now recognized as Snijders Blok-Campeau syndrome. However, with only three previously-reported patients with variants outside the ATPase/helicase domain, it was unclear if variants outside of this domain caused a clinically similar phenotype. We have analyzed 24 new patients with CHD3 variants, including nine outside the ATPase/helicase domain. All patients were detected with unbiased molecular genetic methods. There is not a significant difference in the clinical or facial features of patients with variants in or outside this domain. These additional patients further expand the clinical and molecular data associated with CHD3 variants. Importantly we conclude that there is not a significant difference in the phenotypic features of patients with various molecular disruptions, including whole gene deletions and duplications, and missense variants outside the ATPase/helicase domain. This data will aid both clinical geneticists and molecular geneticists in the diagnosis of this emerging syndrome.

Published
2020

33. Genome-wide association study identifies 30 loci associated with bipolar disorder

Author

Stahl, EA, Breen, G, Forstner, AJ, McQuillin, A, Ripke, S, Trubetskoy, V, Mattheisen, M, Wang, Y, Coleman, JRI, Gaspar, HA, de Leeuw, CA, Steinberg, S, Pavlides, JMW, Trzaskowski, M, Byrne, EM, Pers, TH, Holmans, PA, Richards, AL, Abbott, L, Agerbo, E, Akil, H, Albani, D, Alliey-Rodriguez, N, Als, TD, Anjorin, A, Antilla, V, Awasthi, S, Badner, JA, Bækvad-Hansen, M, Barchas, JD, Bass, N, Bauer, M, Belliveau, R, Bergen, SE, Pedersen, CB, Bøen, E, Boks, MP, Boocock, J, Budde, M, Bunney, W, Burmeister, M, Bybjerg-Grauholm, J, Byerley, W, Casas, M, Cerrato, F, Cervantes, P, Chambert, K, Charney, AW, Chen, D, Churchhouse, C, Clarke, TK, Coryell, W, Craig, DW, Cruceanu, C, Curtis, D, Czerski, PM, Dale, AM, de Jong, S, Degenhardt, F, Del-Favero, J, DePaulo, JR, Djurovic, S, Dobbyn, AL, Dumont, A, Elvsåshagen, T, Escott-Price, V, Fan, CC, Fischer, SB, Flickinger, M, Foroud, TM, Forty, L, Frank, J, Fraser, C, Freimer, NB, Frisén, L, Gade, K, Gage, D, Garnham, J, Giambartolomei, C, Pedersen, MG, Goldstein, J, Gordon, SD, Gordon-Smith, K, Green, EK, Green, MJ, Greenwood, TA, Grove, J, Guan, W, Guzman-Parra, J, Hamshere, ML, Hautzinger, M, Heilbronner, U, Herms, S, Hipolito, M, Hoffmann, P, Holland, D, Huckins, L, Jamain, S, Johnson, JS, Juréus, A, Stahl, EA, Breen, G, Forstner, AJ, McQuillin, A, Ripke, S, Trubetskoy, V, Mattheisen, M, Wang, Y, Coleman, JRI, Gaspar, HA, de Leeuw, CA, Steinberg, S, Pavlides, JMW, Trzaskowski, M, Byrne, EM, Pers, TH, Holmans, PA, Richards, AL, Abbott, L, Agerbo, E, Akil, H, Albani, D, Alliey-Rodriguez, N, Als, TD, Anjorin, A, Antilla, V, Awasthi, S, Badner, JA, Bækvad-Hansen, M, Barchas, JD, Bass, N, Bauer, M, Belliveau, R, Bergen, SE, Pedersen, CB, Bøen, E, Boks, MP, Boocock, J, Budde, M, Bunney, W, Burmeister, M, Bybjerg-Grauholm, J, Byerley, W, Casas, M, Cerrato, F, Cervantes, P, Chambert, K, Charney, AW, Chen, D, Churchhouse, C, Clarke, TK, Coryell, W, Craig, DW, Cruceanu, C, Curtis, D, Czerski, PM, Dale, AM, de Jong, S, Degenhardt, F, Del-Favero, J, DePaulo, JR, Djurovic, S, Dobbyn, AL, Dumont, A, Elvsåshagen, T, Escott-Price, V, Fan, CC, Fischer, SB, Flickinger, M, Foroud, TM, Forty, L, Frank, J, Fraser, C, Freimer, NB, Frisén, L, Gade, K, Gage, D, Garnham, J, Giambartolomei, C, Pedersen, MG, Goldstein, J, Gordon, SD, Gordon-Smith, K, Green, EK, Green, MJ, Greenwood, TA, Grove, J, Guan, W, Guzman-Parra, J, Hamshere, ML, Hautzinger, M, Heilbronner, U, Herms, S, Hipolito, M, Hoffmann, P, Holland, D, Huckins, L, Jamain, S, Johnson, JS, and Juréus, A

Abstract

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10 −4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10 −8 ) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

Published
2019

34. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Author

Andlauer, T.F.M. (Till F. M.), Guzman-Parra, J. (Jose), Streit, F. (Fabian), Strohmaier, J. (Jana), González, M.J. (Maria José), Gil Flores, S. (Susana), Cabaleiro Fabeiro, F.J. (Francisco J.), del Río Noriega, F. (Francisco), Perez, F.P. (Fermin Perez), Haro González, J. (Jesus), Orozco Diaz, G. (Guillermo), Diego, Y. (Yolanda) de, Moreno-Küstner, B. (Berta), Auburger, G. (Georg), Degenhardt, F. (Franziska), Heilmann-Heimbach, S. (Stefanie), Herms, S. (Stefan), Hoffmann, P. (Per), Frank, J. (Josef), Foo, J.C. (Jerome C.), Treutlein, J. (Jens), Witt, S.H. (Stephanie H), Cichon, S. (Sven), Kogevinas, M. (Manolis), Stahl, E.A. (Eli A), Breen, G. (Gerome), Forstner, A.J. (Andreas J), McQuillin, A. (Andrew), Ripke, S. (Stephan), Trubetskoy, V. (Vassily), Mattheisen, M. (Manuel), Wang, Y. (Yunpeng), Coleman, J.R.I. (Jonathan R I), Gaspar, H.A. (Héléna A), Leeuw, C. (Christiaan) de, Steinberg, S. (Stacy), Pavlides, J.M.W. (Jennifer M Whitehead), Trzaskowski, M. (Maciej), Pers, T.H. (Tune H), Holmans, P.A. (Peter A.), Abbott, L. (Liam), Agerbo, E. (Esben), Akil, H. (Huda), Albani, D. (Diego), Alliey-Rodriguez, N. (Ney), Als, T.D. (Thomas D), Anjorin, A. (Adebayo), Antilla, V. (Verneri), Awasthi, S. (Swapnil), Badner, J.A. (Judith A), Bækvad-Hansen, M. (Marie), Barchas, J.D. (Jack D), Bass, N. (Nicholas), Bauer, M. (Michael), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Pedersen, C.B. (C.), Bøen, E. (Erlend), Boks, M.P.M. (Marco), Boocock, J. (James), Budde, M. (Monika), Bunney, W.E. (William E), Burmeister, M., Bybjerg-Grauholm, J. (Jonas), Byerley, W.F. (William F), Casas, M. (Miquel), Cerrato, F. (Felecia), Cervantes, P. (Pablo), Chambert, K. (Kimberly), Charney, A.W. (Alexander W), Chen, D. (Danfeng), Churchhouse, C. (Claire), Clarke, T.-K. (Toni-Kim), Coryell, W.H. (William H), Craig, D.W. (David W), Cruceanu, C. (Cristiana), Czerski, P.M., Dale, A.M. (Anders), de Jong, S. (Simone), Del-Favero, J. (Jurgen), DePaulo, J.R. (J Raymond), Djurovic, S. (Srdjan), Dobbyn, A.L. (Amanda L), Dumont, A. (Ashley), Elvsåshagen, T. (Torbjørn), Escott-Price, V. (Valentina), Fan, C.C. (Chun Chieh), Fischer, S.B. (Sascha B), Flickinger, M. (Matthew), Foroud, T.M. (Tatiana M), Forty, L. (Liz), Fraser, C. (Christine), Luben, R.N. (Robert), Frisén, L. (Louise), Gade, K. (Katrin), Gage, D. (Diane), Garnham, J. (Julie), Giambartolomei, C. (Claudia), Pedersen, M.G. (Marianne Giørtz), Goldstein, J.I. (Jacqueline), Gordon, S.D. (Scott D), Gordon-Smith, K. (Katherine), Green, E.K. (Elaine K), Green, M.J. (Melissa J), Greenwood, T.A. (Tiffany A), Grove, J. (Jakob), Guan, W. (Weihua), Parra, J.G. (José Guzman), Hamshere, M.L. (Marian), Hautzinger, M. (Martin), Heilbronner, U. (Urs), Hipolito, M. (Maria), Holland, D. (Dominic), Huckins, L. (Laura), Jamain, S. (Stéphane), Johnson, J.S. (Jessica S), Juréus, A. (Anders), Kandaswamy, R. (Radhika), Karlsson, R. (Robert), Kennedy, J.L. (James L), Kittel-Schneider, S. (Sarah), Knowles, J.A. (James A), Koller, A.C. (Anna C), Kupka, R.W. (Ralph ), Lavebratt, C. (Catharina), Lawrence, J. (Jacob), Lawson, W.B. (William B), Leber, I. (Isabelle), Lee, P.H. (Phil H), Levy, S.E. (Shawn E), Li, J.Z. (Jun Z), Liu, C. (Chunyu), Lucae, S. (Susanne), Maaser, A. (Anna), Macintyre, D.J. (Donald J), Mahon, P.B. (Pamela B), Maier, W. (Wolfgang), Martinsson, L. (Lina), McCarroll, S.A. (Steve), McGuffin, P. (Peter), Mcinnis, M.G. (Melvin G), McKay, J.D. (James D), Medeiros, H. (Helena), Medland, S.E. (Sarah E), Meng, F. (Fan), Milani, L. (Lili), Montgomery, G.W. (Grant W), Morris, D.W. (Derek W), Mühleisen, T.W. (Thomas W), Mullins, N. (Niamh), Nguyen, H. (Hoang), Nievergelt, C.M. (Caroline M), Adolfsson, A.N. (Annelie Nordin), Nwulia, E.A. (Evaristus A), O’Donovan, C. (Claire), Loohuis, L.M.O. (Loes M Olde), Ori, A.P.S. (Anil P S), Oruc, L. (Lilijana), Ösby, U. (Urban), Perlis, R.H. (Roy H), Perry, A. (Amy), Pfennig, A. (Andrea), Potash, J.B. (James B), Purcell, S.M. (Shaun M), Regeer, E.J. (Eline Janet), Reif, A. (Andreas), Reinbold, C.S. (Céline S), Rice, J.P. (John), Richards, A. (Alex), Rivas, F. (Fabio), Rivera, M. (Margarita), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Ryu, J. (Julie), Sánchez-Mora, C. (Cristina), Schatzberg, A.F. (Alan F), Scheftner, W.A. (William A), Schork, N.J. (Nicholas), Weickert, C.S. (Cynthia Shannon), Shehktman, T. (Tatyana), Shilling, P.D. (Paul D), Sigurdsson, E. (Engilbert), Slaney, C. (Claire), Smeland, O.B. (Olav B), Sobell, J.L. (Janet L), Hansen, C.S. (Christine Søholm), Spijker, A.T. (Anne T), Clair, D.S., Steffens, M. (Michael), Strauss, J.S. (John S), Szelinger, S. (Szabolcs), Thompson, R.C. (Robert C), EThorgeirsson, T. (Thorgeir), Vedde, H. (Helmut), Wang, W. (Weiqing), Watson, S.J. (Stanley J), Weickert, T.W. (Thomas W), Xi, S. (Simon), Xu, W. (Wei), Young, A.H. (Allan H), Zandi, P.P. (Peter P), Zhang, P. (Ping), Zöllner, S. (Sebastian), Adolfsson, R., Agartz, I. (Ingrid), Alda, M. (Martin), Backlund, L. (Lena), Baune, B.T. (Bernhard T), Bellivier, F. (Frank), Berrettini, W. (Wade), Biernacka, J.M. (Joanna M), Blackwood, D.H.R. (Douglas), Boehnke, M. (Michael), Børglum, A.D. (Anders D), Corvin, A. (Aiden), Craddock, N. (Nicholas), Daly, M.J. (Mark), Dannlowski, U. (Udo), Esko, T. (Tõnu), Etain, B. (Bruno), Frye, M.A. (Mark A), Fullerton, J.M. (Janice M), Gershon, E.S. (Elliot S), Gill, M. (Michael), Goes, F. (Fernando), Grigoroiu-Serbanescu, M. (Maria), Hauser, J. (J.), Hougaard, D.M. (David M), Hultman, C.M. (Christina), Jones, I. (Ian), Jones, L.A. (Lisa A), Kahn, R. (René), Kirov, G. (George), Landén, M. (Mikael), Leboyer, M. (Marion), Lewis, C.M. (Cathryn), Li, Q.S. (Qingqin S), Lissowska, J. (Jolanta), Martin, N.G. (Nicholas), Mayoral, F. (Fermin), McElroy, S.L. (Susan L), McIntosh, A.M. (Andrew), Mcmahon, F.J. (Francis J), Melle, I. (Ingrid), Metspalu, A. (Andres), Mitchell, P.B. (Philip B), Morken, G. (Gunnar), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (Bertram), Myers, R.H. (Richard), Neale, B.M. (Benjamin), Nimgaonkar, V. (Vishwajit), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C), Oedegaard, K.J. (Ketil J), Owen, M.J. (Michael J), Paciga, S.A. (Sara A), Pato, C. (Carlos), Posthuma, D. (Danielle), Ramos-Quiroga, J.A. (Josep Antoni), Ribasés, M. (Marta), Rietschel, M. (Marcella), Rouleau, G.A. (Guy A), Schalling, M. (Martin), Schofield, P.R. (Peter R), Schulze, T.G. (Thomas G), Serretti, A. (Alessandro), Smoller, J.W., Stefansson, H. (Hreinn), Zwart, J-A. (John-Anker), Stordal, E. (Eystein), Sullivan, P.F. (Patrick F), Turecki, G. (Gustavo), Vaaler, A.E. (Arne E), Vieta, E. (Eduard), Vincent, J.B. (John B), Werge, T.M. (Thomas), Nurnberger, J.I. (John I), Wray, N.R. (Naomi), Florio, A.D. (Arianna Di), Edenberg, H.J. (Howard), Ophoff, R.A. (Roel), Scott, L.J. (Laura J), Andreassen, O.A. (Ole), Kelsoe, J.R. (John), Sklar, P. (Pamela), Wray, N.R. (Naomi R), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J), Air, T.M. (Tracy M), Bacanu, S.A. (Silviu), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B), Binder, E.B. (Elisabeth), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E), Davies, G. (Gail), Deary, I.J. (Ian J), Degenhardt, F., Derks, E.M. (Eske M), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K), Foo, J.C. (Jerome C), Goes, F.S. (Fernando S), Gordon, S.D. (Scott D.), Hall, L.S. (Lynsey S), Hansen, T.F. (Thomas F), Hickie, I.B. (Ian), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M), Ising, M. (Marcus), Jansen, R. (Rick), Jones, I., Jones, L. (Louisa), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), MacIntyre, D.J. (Donald J), MacKinnon, D.F. (Dean F), Maier, R.M. (Robert M), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Mcguffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel M), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Mondimore, F.M. (Francis M), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (Carsten Bøcker), Peterson, R.E. (Roseann E), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Quiroz, J.A. (Jorge A), Qvist, P. (Per), Rice, J.P. (John P), Riley, B.P. (Brien P.), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C), Shen, L. (Li), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sinnamon, G.C.B. (Grant C B), Smith, A.V. (Davey), Smith, D.J. (Daniel J), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A), Thorgeirsson, T.E. (Thorgeir E), Traylor, M. (Matthew), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M), Viktorin, A. (Alexander), Visscher, P.M. (Peter M), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Wu, Y. (Yang), Xi, H.S. (Hualin S), Yang, J. (Joanna), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Domenici, E. (Enrico), Domschke, K. (Katharina), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas G), McIntosh, A.M. (Andrew M), Mors, O., Müller-Myhsok, B. (B.), Nöthen, M.M. (Markus M), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Porteous, D.J. (David J.), Preisig, M. (Martin), Schaefer, C. (Catherine), Smoller, J.W. (Jordan W), Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn M), Levinson, D.F. (Douglas F.), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick), Mayoral, F. (Fermín), Muller-Myhsok, B. (B.), Forstner, A.J. (Andreas J.), Nöthen, M.M. (Markus M.), Andlauer, T.F.M. (Till F. M.), Guzman-Parra, J. (Jose), Streit, F. (Fabian), Strohmaier, J. (Jana), González, M.J. (Maria José), Gil Flores, S. (Susana), Cabaleiro Fabeiro, F.J. (Francisco J.), del Río Noriega, F. (Francisco), Perez, F.P. (Fermin Perez), Haro González, J. (Jesus), Orozco Diaz, G. (Guillermo), Diego, Y. (Yolanda) de, Moreno-Küstner, B. (Berta), Auburger, G. (Georg), Degenhardt, F. (Franziska), Heilmann-Heimbach, S. (Stefanie), Herms, S. (Stefan), Hoffmann, P. (Per), Frank, J. (Josef), Foo, J.C. (Jerome C.), Treutlein, J. (Jens), Witt, S.H. (Stephanie H), Cichon, S. (Sven), Kogevinas, M. (Manolis), Stahl, E.A. (Eli A), Breen, G. (Gerome), Forstner, A.J. (Andreas J), McQuillin, A. (Andrew), Ripke, S. (Stephan), Trubetskoy, V. (Vassily), Mattheisen, M. (Manuel), Wang, Y. (Yunpeng), Coleman, J.R.I. (Jonathan R I), Gaspar, H.A. (Héléna A), Leeuw, C. (Christiaan) de, Steinberg, S. (Stacy), Pavlides, J.M.W. (Jennifer M Whitehead), Trzaskowski, M. (Maciej), Pers, T.H. (Tune H), Holmans, P.A. (Peter A.), Abbott, L. (Liam), Agerbo, E. (Esben), Akil, H. (Huda), Albani, D. (Diego), Alliey-Rodriguez, N. (Ney), Als, T.D. (Thomas D), Anjorin, A. (Adebayo), Antilla, V. (Verneri), Awasthi, S. (Swapnil), Badner, J.A. (Judith A), Bækvad-Hansen, M. (Marie), Barchas, J.D. (Jack D), Bass, N. (Nicholas), Bauer, M. (Michael), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Pedersen, C.B. (C.), Bøen, E. (Erlend), Boks, M.P.M. (Marco), Boocock, J. (James), Budde, M. (Monika), Bunney, W.E. (William E), Burmeister, M., Bybjerg-Grauholm, J. (Jonas), Byerley, W.F. (William F), Casas, M. (Miquel), Cerrato, F. (Felecia), Cervantes, P. (Pablo), Chambert, K. (Kimberly), Charney, A.W. (Alexander W), Chen, D. (Danfeng), Churchhouse, C. (Claire), Clarke, T.-K. (Toni-Kim), Coryell, W.H. (William H), Craig, D.W. (David W), Cruceanu, C. (Cristiana), Czerski, P.M., Dale, A.M. (Anders), de Jong, S. (Simone), Del-Favero, J. (Jurgen), DePaulo, J.R. (J Raymond), Djurovic, S. (Srdjan), Dobbyn, A.L. (Amanda L), Dumont, A. (Ashley), Elvsåshagen, T. (Torbjørn), Escott-Price, V. (Valentina), Fan, C.C. (Chun Chieh), Fischer, S.B. (Sascha B), Flickinger, M. (Matthew), Foroud, T.M. (Tatiana M), Forty, L. (Liz), Fraser, C. (Christine), Luben, R.N. (Robert), Frisén, L. (Louise), Gade, K. (Katrin), Gage, D. (Diane), Garnham, J. (Julie), Giambartolomei, C. (Claudia), Pedersen, M.G. (Marianne Giørtz), Goldstein, J.I. (Jacqueline), Gordon, S.D. (Scott D), Gordon-Smith, K. (Katherine), Green, E.K. (Elaine K), Green, M.J. (Melissa J), Greenwood, T.A. (Tiffany A), Grove, J. (Jakob), Guan, W. (Weihua), Parra, J.G. (José Guzman), Hamshere, M.L. (Marian), Hautzinger, M. (Martin), Heilbronner, U. (Urs), Hipolito, M. (Maria), Holland, D. (Dominic), Huckins, L. (Laura), Jamain, S. (Stéphane), Johnson, J.S. (Jessica S), Juréus, A. (Anders), Kandaswamy, R. (Radhika), Karlsson, R. (Robert), Kennedy, J.L. (James L), Kittel-Schneider, S. (Sarah), Knowles, J.A. (James A), Koller, A.C. (Anna C), Kupka, R.W. (Ralph ), Lavebratt, C. (Catharina), Lawrence, J. (Jacob), Lawson, W.B. (William B), Leber, I. (Isabelle), Lee, P.H. (Phil H), Levy, S.E. (Shawn E), Li, J.Z. (Jun Z), Liu, C. (Chunyu), Lucae, S. (Susanne), Maaser, A. (Anna), Macintyre, D.J. (Donald J), Mahon, P.B. (Pamela B), Maier, W. (Wolfgang), Martinsson, L. (Lina), McCarroll, S.A. (Steve), McGuffin, P. (Peter), Mcinnis, M.G. (Melvin G), McKay, J.D. (James D), Medeiros, H. (Helena), Medland, S.E. (Sarah E), Meng, F. (Fan), Milani, L. (Lili), Montgomery, G.W. (Grant W), Morris, D.W. (Derek W), Mühleisen, T.W. (Thomas W), Mullins, N. (Niamh), Nguyen, H. (Hoang), Nievergelt, C.M. (Caroline M), Adolfsson, A.N. (Annelie Nordin), Nwulia, E.A. (Evaristus A), O’Donovan, C. (Claire), Loohuis, L.M.O. (Loes M Olde), Ori, A.P.S. (Anil P S), Oruc, L. (Lilijana), Ösby, U. (Urban), Perlis, R.H. (Roy H), Perry, A. (Amy), Pfennig, A. (Andrea), Potash, J.B. (James B), Purcell, S.M. (Shaun M), Regeer, E.J. (Eline Janet), Reif, A. (Andreas), Reinbold, C.S. (Céline S), Rice, J.P. (John), Richards, A. (Alex), Rivas, F. (Fabio), Rivera, M. (Margarita), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Ryu, J. (Julie), Sánchez-Mora, C. (Cristina), Schatzberg, A.F. (Alan F), Scheftner, W.A. (William A), Schork, N.J. (Nicholas), Weickert, C.S. (Cynthia Shannon), Shehktman, T. (Tatyana), Shilling, P.D. (Paul D), Sigurdsson, E. (Engilbert), Slaney, C. (Claire), Smeland, O.B. (Olav B), Sobell, J.L. (Janet L), Hansen, C.S. (Christine Søholm), Spijker, A.T. (Anne T), Clair, D.S., Steffens, M. (Michael), Strauss, J.S. (John S), Szelinger, S. (Szabolcs), Thompson, R.C. (Robert C), EThorgeirsson, T. (Thorgeir), Vedde, H. (Helmut), Wang, W. (Weiqing), Watson, S.J. (Stanley J), Weickert, T.W. (Thomas W), Xi, S. (Simon), Xu, W. (Wei), Young, A.H. (Allan H), Zandi, P.P. (Peter P), Zhang, P. (Ping), Zöllner, S. (Sebastian), Adolfsson, R., Agartz, I. (Ingrid), Alda, M. (Martin), Backlund, L. (Lena), Baune, B.T. (Bernhard T), Bellivier, F. (Frank), Berrettini, W. (Wade), Biernacka, J.M. (Joanna M), Blackwood, D.H.R. (Douglas), Boehnke, M. (Michael), Børglum, A.D. (Anders D), Corvin, A. (Aiden), Craddock, N. (Nicholas), Daly, M.J. (Mark), Dannlowski, U. (Udo), Esko, T. (Tõnu), Etain, B. (Bruno), Frye, M.A. (Mark A), Fullerton, J.M. (Janice M), Gershon, E.S. (Elliot S), Gill, M. (Michael), Goes, F. (Fernando), Grigoroiu-Serbanescu, M. (Maria), Hauser, J. (J.), Hougaard, D.M. (David M), Hultman, C.M. (Christina), Jones, I. (Ian), Jones, L.A. (Lisa A), Kahn, R. (René), Kirov, G. (George), Landén, M. (Mikael), Leboyer, M. (Marion), Lewis, C.M. (Cathryn), Li, Q.S. (Qingqin S), Lissowska, J. (Jolanta), Martin, N.G. (Nicholas), Mayoral, F. (Fermin), McElroy, S.L. (Susan L), McIntosh, A.M. (Andrew), Mcmahon, F.J. (Francis J), Melle, I. (Ingrid), Metspalu, A. (Andres), Mitchell, P.B. (Philip B), Morken, G. (Gunnar), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (Bertram), Myers, R.H. (Richard), Neale, B.M. (Benjamin), Nimgaonkar, V. (Vishwajit), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C), Oedegaard, K.J. (Ketil J), Owen, M.J. (Michael J), Paciga, S.A. (Sara A), Pato, C. (Carlos), Posthuma, D. (Danielle), Ramos-Quiroga, J.A. (Josep Antoni), Ribasés, M. (Marta), Rietschel, M. (Marcella), Rouleau, G.A. (Guy A), Schalling, M. (Martin), Schofield, P.R. (Peter R), Schulze, T.G. (Thomas G), Serretti, A. (Alessandro), Smoller, J.W., Stefansson, H. (Hreinn), Zwart, J-A. (John-Anker), Stordal, E. (Eystein), Sullivan, P.F. (Patrick F), Turecki, G. (Gustavo), Vaaler, A.E. (Arne E), Vieta, E. (Eduard), Vincent, J.B. (John B), Werge, T.M. (Thomas), Nurnberger, J.I. (John I), Wray, N.R. (Naomi), Florio, A.D. (Arianna Di), Edenberg, H.J. (Howard), Ophoff, R.A. (Roel), Scott, L.J. (Laura J), Andreassen, O.A. (Ole), Kelsoe, J.R. (John), Sklar, P. (Pamela), Wray, N.R. (Naomi R), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J), Air, T.M. (Tracy M), Bacanu, S.A. (Silviu), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B), Binder, E.B. (Elisabeth), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E), Davies, G. (Gail), Deary, I.J. (Ian J), Degenhardt, F., Derks, E.M. (Eske M), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K), Foo, J.C. (Jerome C), Goes, F.S. (Fernando S), Gordon, S.D. (Scott D.), Hall, L.S. (Lynsey S), Hansen, T.F. (Thomas F), Hickie, I.B. (Ian), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M), Ising, M. (Marcus), Jansen, R. (Rick), Jones, I., Jones, L. (Louisa), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), MacIntyre, D.J. (Donald J), MacKinnon, D.F. (Dean F), Maier, R.M. (Robert M), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Mcguffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel M), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Mondimore, F.M. (Francis M), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (Carsten Bøcker), Peterson, R.E. (Roseann E), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Quiroz, J.A. (Jorge A), Qvist, P. (Per), Rice, J.P. (John P), Riley, B.P. (Brien P.), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C), Shen, L. (Li), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sinnamon, G.C.B. (Grant C B), Smith, A.V. (Davey), Smith, D.J. (Daniel J), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A), Thorgeirsson, T.E. (Thorgeir E), Traylor, M. (Matthew), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M), Viktorin, A. (Alexander), Visscher, P.M. (Peter M), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Wu, Y. (Yang), Xi, H.S. (Hualin S), Yang, J. (Joanna), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Domenici, E. (Enrico), Domschke, K. (Katharina), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas G), McIntosh, A.M. (Andrew M), Mors, O., Müller-Myhsok, B. (B.), Nöthen, M.M. (Markus M), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Porteous, D.J. (David J.), Preisig, M. (Martin), Schaefer, C. (Catherine), Smoller, J.W. (Jordan W), Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn M), Levinson, D.F. (Douglas F.), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick), Mayoral, F. (Fermín), Muller-Myhsok, B. (B.), Forstner, A.J. (Andreas J.), and Nöthen, M.M. (Markus M.)

Abstract

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

Published
2019
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42. Improving genetic prediction by leveraging genetic correlations among human diseases and traits

Author

Maier, R. M., Zhu, Z., Lee, S. H., Trzaskowski, M., Ruderfer, D. M., Stahl, E. A., Ripke, S., Wray, N. R., Yang, J., Visscher, P. M., Robinson, M. R., Forstner, A. J., Mcquillin, A., Trubetskoy, V., Wang, W., Wang, Y., Coleman, J. R. I., Gaspar, H. A., Leeuw, C. A., Whitehead Pavlides, J. M., Olde Loohuis, L. M., Pers, T. H., Lee, P. H., Charney, A. W., Dobbyn, A. L., Huckins, L., Boocock, J., Giambartolomei, C., Roussos, P., Mullins, N., Awasthi, S., Agerbo, E., Als, T. D., Pedersen, C. B., Grove, J., Kupka, R., Regeer, E. J., Anjorin, A., Casas, M., Mahon, P. B., Allardyce, J., Escott-Price, V., Forty, L., Fraser, C., Kogevinas, M., Frank, J., Streit, F., Strohmaier, J., Treutlein, J., Witt, S. H., Kennedy, J. L., Strauss, J. S., Garnham, J., O Donovan, C., Slaney, C., Steinberg, S., Thorgeirsson, T. E., Hautzinger, M., Steffens, M., Perlis, R. H., Sánchez-Mora, C., Hipolito, M., Lawson, W. B., Nwulia, E. A., Levy, S. E., Foroud, T. M., Jamain, S., Young, A. H., Mckay, J. D., Albani, D., Zandi, P., Potash, J. B., Zhang, P., Raymond Depaulo, J., Bergen, S. E., Juréus, A., Karlsson, R., Kandaswamy, R., Mcguffin, P., Rivera, M., Lissowska, J., Cruceanu, C., Lucae, S., Cervantes, P., Budde, M., Gade, K., Heilbronner, U., Pedersen, M. G., Morris, D. W., Weickert, C. S., Weickert, T. W., Macintyre, D. J., Lawrence, J., Elvsåshagen, T., Smeland, O. B., Djurovic, S., Xi, S., Green, E. K., Czerski, P. M., Hauser, J., Xu, W., Vedder, H., Oruc, L., Spijker, A. T., Gordon, S. D., Medland, S. E., Curtis, D., Mühleisen, T. W., Badner, J. A., Scheftner, W. A., Sigurdsson, E., Schork, N. J., Schatzberg, A. F., Bækvad-Hansen, M., Bybjerg-Grauholm, J., Hansen, C. S., Knowles, J. A., Szelinger, S., Montgomery, G. W., Boks, M., Adolfsson, A. N., Hoffmann, P., Bauer, M., Pfennig, A., Leber, M., Kittel-Schneider, S., Reif, A., Del-Favero, J., Fischer, S. B., Herms, S., Reinbold, C. S., Degenhardt, F., Koller, A. C., Maaser, A., Ori, A. P. S., Dale, A. M., Fan, C. C., Greenwood, T. A., Nievergelt, C. M., Shehktman, T., Shilling, P. D., Byerley, W., Bunney, W., Alliey-Rodriguez, N., Clarke, T. K., Liu, C., Coryell, W., Akil, H., Burmeister, M., Flickinger, M., Li, J. Z., Mcinnis, M. G., Meng, F., Thompson, R. C., Watson, S. J., Zollner, S., Guan, W., Green, M. J., Craig, D., Sobell, J. L., Milani, L., Gordon-Smith, Katherine, Knott, Sarah, Perry, Amy, Parra, J. G., Mayoral, F., Rivas, F., Rice, J. P., Barchas, J. D., Børglum, A. D., Mortensen, P. B., Mors, O., Grigoroiu-Serbanescu, M., Bellivier, F., Etain, B., Leboyer, M., Ramos-Quiroga, J. A., Agartz, I., Amin, F., Azevedo, M. H., Bass, N., Black, D. W., Blackwood, D. H. R., Bruggeman, R., Buccola, N. G., Choudhury, K., Cloninger, C. R., Corvin, A., Craddock, N., Daly, M. J., Datta, S., Donohoe, G. J., Duan, J., Dudbridge, F., Fanous, A., Freedman, R., Freimer, N. B., Friedl, M., Gill, M., Gurling, H., Haan, L., Hamshere, M. L., Hartmann, A. M., Holmans, P. A., Kahn, R. S., Keller, M. C., Kenny, E., Kirov, G. K., Krabbendam, L., Krasucki, R., Lencz, T., Levinson, D. F., Lieberman, J. A., Lin, D. -Y, Linszen, D. H., Magnusson, P. K. E., Maier, W., Malhotra, A. K., Mattheisen, M., Mattingsdal, M., Mccarroll, S. A., Medeiros, H., Melle, I., Milanova, V., Myin-Germeys, I., Neale, B. M., Ophoff, R. A., Owen, M. J., Pimm, J., Purcell, S. M., Puri, V., Digby Quested, Rossin, L., Sanders, A. R., Shi, J., Sklar, P., St Clair, D., Stroup, T. S., Os, J., Wiersma, D., Zammit, S., Maier, Robert M, Zhu, Zhihong, Lee, Sang Hong, Trzaskowski, Maciej, Ruderfer, Douglas M, Stahl, Eli A, Ripke, Stephan, Wray, Naomi R, Yang, Jian, Visscher, Peter M, Robinson, Matthew R, Bipolar Disorder Working Grp Psy, Schizophrenia Working Grp Psychiat, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, and Psychiatry

Subjects
0301 basic medicine, Bipolar Disorder, Chemistry(all), Science, General Physics and Astronomy, Genomics, Genome-wide association study, Computational biology, Biology, Physics and Astronomy(all), Risk Assessment, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Article, predictive medicine, quantitative trait, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Pleiotropy, Genetic Pleiotropy, Humans, Genetic Predisposition to Disease, lcsh:Science, Multidisciplinary, Models, Statistical, Bipolar Disorder/genetics, Genome-Wide Association Study, Schizophrenia/genetics, Biochemistry, Genetics and Molecular Biology(all), General Chemistry, Precision medicine, R1, Biobank, 3. Good health, genome wide association studies, 030104 developmental biology, Trait, Schizophrenia, statistical methods, lcsh:Q, Risk assessment, 030217 neurology & neurosurgery, Genetics and Molecular Biology(all)
Abstract

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7% for height to 47% for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait., Genetic prediction of complex traits so far has limited accuracy because of insufficient understanding of the genetic risk. Here, Maier et al. develop an improved method for trait prediction that makes use of genetic correlations between traits and apply it to summary statistics of psychiatric diseases.

Published
2018

43. Collaborative meta-Analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Author

Culverhouse, R.C. Saccone, N.L. Horton, A.C. Ma, Y. Anstey, K.J. Banaschewski, T. Burmeister, M. Cohen-Woods, S. Etain, B. Fisher, H.L. Goldman, N. Guillaume, S. Horwood, J. Juhasz, G. Lester, K.J. Mandelli, L. Middeldorp, C.M. Olié, E. Villafuerte, S. Air, T.M. Araya, R. Bowes, L. Burns, R. Byrne, E.M. Coffey, C. Coventry, W.L. Gawronski, K.A.B. Glei, D. Hatzimanolis, A. Hottenga, J.-J. Jaussent, I. Jawahar, C. Jennen-Steinmetz, C. Kramer, J.R. Lajnef, M. Little, K. Zu Schwabedissen, H.M. Nauck, M. Nederhof, E. Petschner, P. Peyrot, W.J. Schwahn, C. Sinnamon, G. Stacey, D. Tian, Y. Toben, C. Van Der Auwera, S. Wainwright, N. Wang, J.-C. Willemsen, G. Anderson, I.M. Arolt, V. Aslund, C. Bagdy, G. Baune, B.T. Bellivier, F. Boomsma, D.I. Courtet, P. Dannlowski, U. De Geus, E.J.C. Deakin, J.F.W. Easteal, S. Eley, T. Fergusson, D.M. Goate, A.M. Gonda, X. Grabe, H.J. Holzman, C. Johnson, E.O. Kennedy, M. Laucht, M. Martin, N.G. Munafò, M.R. Nilsson, K.W. Oldehinkel, A.J. Olsson, C.A. Ormel, J. Otte, C. Patton, G.C. Penninx, B.W.J.H. Ritchie, K. Sarchiapone, M. Scheid, J.M. Serretti, A. Smit, J.H. Stefanis, N.C. Surtees, P.G. Völzke, H. Weinstein, M. Whooley, M. Nurnberger, J.I., Jr. Breslau, N. Bierut, L.J.

Abstract

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-Analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-Analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-Analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Published
2018

44. La inactivación de GLI1 causa alteraciones del desarrollo solapantes con el Síndrome de Ellis-vanCreveld

Author

Palencia-Campos, Adrian, Ullah, Asmat, Nevado, Julian, Yildirim, Ruken, Unal, Edip, Ciorraga, Maria, Barruz, Pilar, Chico, Lucia, Piceci-Sparascio, Francesca, Guida, Valentina, De Luca, Alessandro, Kayserili, Hülya, Ullah, Irfan, Burmeister, M., Lapunzina, Pablo, Ahmad, W., Morales, Aixa V., and Ruiz-Pérez, Victor L.

Abstract

Resumen del trabajo presentado a la XI Reunión Anual CIBERER, celebrada en Castelldefels, Barcelona del 12 al 14 de marzo de 2018., Los factores transcripcionales GLI1, GLI2 y GLI3 actúan en el desarrollo embrionario como mediadores de los morfógenos Hedgehog (Hh). En consecuencia, variantes deletéreas en GLI2 y GLI3 han sido reportadas como responsables de defectos congénitos. Sin embargo, hasta la fecha no se habían descrito mutaciones en GLI1, por lo que el papel de este gen en el desarrollo humano permanecía desconocido. Aquí presentamos 8 pacientes de tres familias distintas con mutaciones en GLI1 y características clínicas similares a las del Síndrome de Ellis-van Creveld (EvC), una enfermedad causada por la disminución de la actividad de la vía de Hh. Dos familias portaban mutaciones de fin de mensaje en el último exón del gen y la tercera un codón de parada en la región N-terminal. El análisis de fibroblastos de uno de los pacientes con mutaciones en el último exón demostró que las células de este paciente sintetizan la proteína truncada correspondiente e inducen su expresión en respuesta a un agonista químico de Hh. Sin embargo, ensayos “in vivo” y en cultivo celular revelaron que la actividad transcripcional de la proteína mutante se encontraba drásticamente disminuida. Consistentemente, las células del paciente presentaron menor expresión de la diana de Hh, PTCH1. Este trabajo muestra que la inactivación de GLI1 da lugar a alteraciones del desarrollo que varían desde polidactilia postaxial aislada hasta fenotipos solapantes con EvC, a la vez que pone de manifiesto que todos los miembros de la triada GLI son necesarios en el desarrollo humano.

Published
2018

47. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Author

Culverhouse, R. C., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., Burmeister, M., Cohen-Woods, S., Etain, B., Fisher, H. L., Goldman, N., Guillaume, S., Horwood, J., Juhasz, G., Lester, K. J., Mandelli, L., Middeldorp, C. M., Olie, E., Villafuerte, S., Air, T. M., Araya, R., Bowes, L., Burns, R., Byrne, E. M., Coffey, C., Coventry, W. L., Gawronski, K. A. B., Glei, D., Hatzimanolis, A., Hottenga, J-J, Jaussent, I., Jawahar, C., Jennen-Steinmetz, C., Kramer, J. R., Lajnef, M., Little, K., zu Schwabedissen, H. M., Nauck, M., Nederhof, E., Petschner, P., Peyrot, W. J., Schwahn, C., Sinnamon, G., Stacey, D., Tian, Y., Toben, C., Van der Auwera, S., Wainwright, N., Wang, J-C, Willemsen, G., Anderson, I. M., Arolt, V., Åslund, Cecilia, Bagdy, G., Baune, B. T., Bellivier, F., Boomsma, D. I., Courtet, P., Dannlowski, U., de Geus, E. J. C., Deakin, J. F. W., Easteal, S., Eley, T., Fergusson, D. M., Goate, A. M., Gonda, X., Grabe, H. J., Holzman, C., Johnson, E. O., Kennedy, M., Laucht, M., Martin, N. G., Munafo, M. R., Nillson, Kent W., Oldehinkel, A. J., Olsson, C. A., Ormel, J., Otte, C., Patton, G. C., Penninx, B. W. J. H., Ritchie, K., Sarchiapone, M., Scheid, J. M., Serretti, A., Smit, J. H., Stefanis, N. C., Surtees, P. G., Voelzke, H., Weinstein, M., Whooley, M., Nurnberger, J. I., Jr., Breslau, N., Bierut, L. J., Culverhouse, R. C., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., Burmeister, M., Cohen-Woods, S., Etain, B., Fisher, H. L., Goldman, N., Guillaume, S., Horwood, J., Juhasz, G., Lester, K. J., Mandelli, L., Middeldorp, C. M., Olie, E., Villafuerte, S., Air, T. M., Araya, R., Bowes, L., Burns, R., Byrne, E. M., Coffey, C., Coventry, W. L., Gawronski, K. A. B., Glei, D., Hatzimanolis, A., Hottenga, J-J, Jaussent, I., Jawahar, C., Jennen-Steinmetz, C., Kramer, J. R., Lajnef, M., Little, K., zu Schwabedissen, H. M., Nauck, M., Nederhof, E., Petschner, P., Peyrot, W. J., Schwahn, C., Sinnamon, G., Stacey, D., Tian, Y., Toben, C., Van der Auwera, S., Wainwright, N., Wang, J-C, Willemsen, G., Anderson, I. M., Arolt, V., Åslund, Cecilia, Bagdy, G., Baune, B. T., Bellivier, F., Boomsma, D. I., Courtet, P., Dannlowski, U., de Geus, E. J. C., Deakin, J. F. W., Easteal, S., Eley, T., Fergusson, D. M., Goate, A. M., Gonda, X., Grabe, H. J., Holzman, C., Johnson, E. O., Kennedy, M., Laucht, M., Martin, N. G., Munafo, M. R., Nillson, Kent W., Oldehinkel, A. J., Olsson, C. A., Ormel, J., Otte, C., Patton, G. C., Penninx, B. W. J. H., Ritchie, K., Sarchiapone, M., Scheid, J. M., Serretti, A., Smit, J. H., Stefanis, N. C., Surtees, P. G., Voelzke, H., Weinstein, M., Whooley, M., Nurnberger, J. I., Jr., Breslau, N., and Bierut, L. J.

Abstract

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Published
2018
Full Text
View/download PDF

48. Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Author

Ruderfer, DM, Ripke, S, McQuillin, A, Boocock, J, Stahl, EA, Pavlides, JMW, Mullins, N, Charney, AW, Ori, APS, Loohuis, LMO, Domenici, E, Di Florio, A, Papiol, S, Kalman, JL, Trubetskoy, V, Adolfsson, R, Agartz, I, Agerbo, E, Akil, H, Albani, D, Albus, M, Alda, M, Alexander, M, Alliey-Rodriguez, N, Als, TD, Amin, F, Anjorin, A, Arranz, MJ, Awasthi, S, Bacanu, SA, Badner, JA, Baekvad-Hansen, M, Bakker, S, Band, G, Barchas, JD, Barroso, I, Bass, N, Bauer, M, Baune, BT, Begemann, M, Bellenguez, C, Belliveau, RA, Bellivier, F, Bender, S, Bene, J, Bergen, SE, Berrettini, WH, Bevilacqua, E, Biernacka, JM, Bigdeli, TB, Black, DW, Blackburn, H, Blackwell, JM, Blackwood, DHR, Pedersen, CB, Boehnke, M, Boks, M, Borglum, AD, Bramon, E, Breen, G, Brown, MA, Bruggeman, R, Buccola, NG, Buckner, RL, Budde, M, Bulik-Sullivan, B, Bumpstead, SJ, Bunney, W, Burmeister, M, Buxbaum, JD, Bybjerg-Grauholm, J, Byerley, W, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Casas, JP, Casas, M, Catts, SV, Cervantes, P, Chambert, KD, Chan, RCK, Chen, EYH, Chen, RYL, Cheng, W, Cheung, EFC, Chong, SA, Clarke, TK, Cloninger, CR, Cohen, D, Cohen, N, Coleman, JRI, Collier, DA, Cormican, P, Coryell, W, Craddock, N, Craig, DW, Ruderfer, DM, Ripke, S, McQuillin, A, Boocock, J, Stahl, EA, Pavlides, JMW, Mullins, N, Charney, AW, Ori, APS, Loohuis, LMO, Domenici, E, Di Florio, A, Papiol, S, Kalman, JL, Trubetskoy, V, Adolfsson, R, Agartz, I, Agerbo, E, Akil, H, Albani, D, Albus, M, Alda, M, Alexander, M, Alliey-Rodriguez, N, Als, TD, Amin, F, Anjorin, A, Arranz, MJ, Awasthi, S, Bacanu, SA, Badner, JA, Baekvad-Hansen, M, Bakker, S, Band, G, Barchas, JD, Barroso, I, Bass, N, Bauer, M, Baune, BT, Begemann, M, Bellenguez, C, Belliveau, RA, Bellivier, F, Bender, S, Bene, J, Bergen, SE, Berrettini, WH, Bevilacqua, E, Biernacka, JM, Bigdeli, TB, Black, DW, Blackburn, H, Blackwell, JM, Blackwood, DHR, Pedersen, CB, Boehnke, M, Boks, M, Borglum, AD, Bramon, E, Breen, G, Brown, MA, Bruggeman, R, Buccola, NG, Buckner, RL, Budde, M, Bulik-Sullivan, B, Bumpstead, SJ, Bunney, W, Burmeister, M, Buxbaum, JD, Bybjerg-Grauholm, J, Byerley, W, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Casas, JP, Casas, M, Catts, SV, Cervantes, P, Chambert, KD, Chan, RCK, Chen, EYH, Chen, RYL, Cheng, W, Cheung, EFC, Chong, SA, Clarke, TK, Cloninger, CR, Cohen, D, Cohen, N, Coleman, JRI, Collier, DA, Cormican, P, Coryell, W, Craddock, N, and Craig, DW

Abstract

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.

Published
2018

49. Collaborative meta-Analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Author

Culverhouse, RC, Saccone, NL, Horton, AC, Ma, Y, Anstey, KJ, Banaschewski, T, Burmeister, M, Cohen-Woods, S, Etain, B, Fisher, HL, Goldman, N, Guillaume, S, Horwood, J, Juhasz, G, Lester, KJ, Mandelli, L, Middeldorp, CM, Olié, E, Villafuerte, S, Air, TM, Araya, R, Bowes, L, Burns, R, Byrne, EM, Coffey, C, Coventry, WL, Gawronski, KAB, Glei, D, Hatzimanolis, A, Hottenga, JJ, Jaussent, I, Jawahar, C, Jennen-Steinmetz, C, Kramer, JR, Lajnef, M, Little, K, Zu Schwabedissen, HM, Nauck, M, Nederhof, E, Petschner, P, Peyrot, WJ, Schwahn, C, Sinnamon, G, Stacey, D, Tian, Y, Toben, C, Van Der Auwera, S, Wainwright, N, Wang, JC, Willemsen, G, Anderson, IM, Arolt, V, Aslund, C, Bagdy, G, Baune, BT, Bellivier, F, Boomsma, DI, Courtet, P, Dannlowski, U, De Geus, EJC, Deakin, JFW, Easteal, S, Eley, T, Fergusson, DM, Goate, AM, Gonda, X, Grabe, HJ, Holzman, C, Johnson, EO, Kennedy, M, Laucht, M, Martin, NG, Munafò, MR, Nilsson, KW, Oldehinkel, AJ, Olsson, CA, Ormel, J, Otte, C, Patton, GC, Penninx, BWJH, Ritchie, K, Sarchiapone, M, Scheid, JM, Serretti, A, Smit, JH, Stefanis, NC, Surtees, PG, Völzke, H, Weinstein, M, Whooley, M, Nurnberger, JI, Breslau, N, Bierut, LJ, Culverhouse, RC, Saccone, NL, Horton, AC, Ma, Y, Anstey, KJ, Banaschewski, T, Burmeister, M, Cohen-Woods, S, Etain, B, Fisher, HL, Goldman, N, Guillaume, S, Horwood, J, Juhasz, G, Lester, KJ, Mandelli, L, Middeldorp, CM, Olié, E, Villafuerte, S, Air, TM, Araya, R, Bowes, L, Burns, R, Byrne, EM, Coffey, C, Coventry, WL, Gawronski, KAB, Glei, D, Hatzimanolis, A, Hottenga, JJ, Jaussent, I, Jawahar, C, Jennen-Steinmetz, C, Kramer, JR, Lajnef, M, Little, K, Zu Schwabedissen, HM, Nauck, M, Nederhof, E, Petschner, P, Peyrot, WJ, Schwahn, C, Sinnamon, G, Stacey, D, Tian, Y, Toben, C, Van Der Auwera, S, Wainwright, N, Wang, JC, Willemsen, G, Anderson, IM, Arolt, V, Aslund, C, Bagdy, G, Baune, BT, Bellivier, F, Boomsma, DI, Courtet, P, Dannlowski, U, De Geus, EJC, Deakin, JFW, Easteal, S, Eley, T, Fergusson, DM, Goate, AM, Gonda, X, Grabe, HJ, Holzman, C, Johnson, EO, Kennedy, M, Laucht, M, Martin, NG, Munafò, MR, Nilsson, KW, Oldehinkel, AJ, Olsson, CA, Ormel, J, Otte, C, Patton, GC, Penninx, BWJH, Ritchie, K, Sarchiapone, M, Scheid, JM, Serretti, A, Smit, JH, Stefanis, NC, Surtees, PG, Völzke, H, Weinstein, M, Whooley, M, Nurnberger, JI, Breslau, N, and Bierut, LJ

Abstract

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-Analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-Analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-Analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Published
2018

50. Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Author

de Jong, S, Abdalla Diniz, MJ, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Curtis, C, Newhouse, SJ, Patel, H, Hall, LS, O'Reilly, PF, Belangero, S, Bressan, RA, Breen, G, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, Mcgrath, P, Mcguffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Borglum, AD, Sullivan, PF, Meier, S, Strauss, J, Xu, W, Vincent, JB, Matthews, K, Ferreira, M, O'Dushlaine, C, Purcell, S, Raychaudhuri, S, Ruderfer, DM, Sklar, P, Scott, LJ, Flickinger, M, Burmeister, M, Li, J, Guan, W, Absher, D, Thompson, RC, Meng, FG, Schatzberg, AF, Bunney, WE, Barchas, JD, Watson, SJ, Myers, RM, Akil, H, Boehnke, M, Chambert, K, Moran, J, Scolnick, E, Djurovic, S, Melle, I, Morken, G, Corvin, A, Anjorin, A, Kandaswamy, R, Lawrence, J, McLean, AW, Pickard, BS, Bergen, SE, Nimgaonkar, V, Landen, M, Schalling, M, Osby, U, Backlund, L, Frisen, L, Langstrom, N, Stahl, E, Dobbyn, A, Jamain, S, Etain, B, Bellivier, F, Leber, M, Maaser, A, Fischer, SB, Reinbold, CS, Kittel-Schneider, S, Fullerton, JM, Oruc, L, Para, JG, Mayoral, F, Rivas, F, Czerski, PM, Kammerer-Ciernioch, J, Vedder, H, Borrmann-Hassenbach, M, Pfennig, A, Brennan, P, McKay, JD, Kogevinas, M, Schwarz, M, Schofield, PR, Muehleisen, TW, Schumacher, J, Bauer, M, Wright, A, Mitchell, PB, Hautzinger, M, Kelsoe, JR, Greenwood, TA, Nievergelt, CM, Shilling, PD, Smith, EN, Bloss, CS, Edenberg, HJ, Koller, DL, Gershon, ES, Liu, C, Badner, JA, Scheftner, WA, Lawson, WB, Nwulia, EA, Hipolito, M, Coryell, W, Rice, J, Byerley, W, McMahon, FJ, Lohoff, FW, Zandi, PP, Mahon, PB, McInnis, MG, Zollner, S, Zhang, P, Szelinger, S, St Clair, D, Caesar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Kirov, G, Nikolov, I, Collier, DA, Elkin, A, Williamson, R, Young, AH, Ferrier, IN, Milanova, V, Alda, M, Cervantes, P, Cruceanu, C, Rouleau, GA, Turecki, G, Paciga, S, Winslow, AR, Grigoroiu-Serbanescu, M, Ophoff, R, Adolfsson, R, Adolfsson, AN, Del-Favero, J, Pato, C, Biernacka, JM, Frye, MA, Morris, D, Schork, NJ, Reif, A, Lissowska, J, Hauser, J, Szeszenia-Dabrowska, N, McGhee, K, Quinn, E, Moskvina, V, Holmans, PA, Farmer, A, Kennedy, JL, Andreassen, OA, Mattingsdal, M, Bass, NJ, Gurling, H, McQuillin, A, Breuer, R, Hultman, C, Lichtenstein, P, Huckins, LM, Leboyer, M, Lathrop, M, Nurnberger, J, Steffens, M, Foroud, TM, Berrettini, WH, Craig, DW, Shi, J, de Jong, S, Abdalla Diniz, MJ, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Curtis, C, Newhouse, SJ, Patel, H, Hall, LS, O'Reilly, PF, Belangero, S, Bressan, RA, Breen, G, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, Mcgrath, P, Mcguffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Borglum, AD, Sullivan, PF, Meier, S, Strauss, J, Xu, W, Vincent, JB, Matthews, K, Ferreira, M, O'Dushlaine, C, Purcell, S, Raychaudhuri, S, Ruderfer, DM, Sklar, P, Scott, LJ, Flickinger, M, Burmeister, M, Li, J, Guan, W, Absher, D, Thompson, RC, Meng, FG, Schatzberg, AF, Bunney, WE, Barchas, JD, Watson, SJ, Myers, RM, Akil, H, Boehnke, M, Chambert, K, Moran, J, Scolnick, E, Djurovic, S, Melle, I, Morken, G, Corvin, A, Anjorin, A, Kandaswamy, R, Lawrence, J, McLean, AW, Pickard, BS, Bergen, SE, Nimgaonkar, V, Landen, M, Schalling, M, Osby, U, Backlund, L, Frisen, L, Langstrom, N, Stahl, E, Dobbyn, A, Jamain, S, Etain, B, Bellivier, F, Leber, M, Maaser, A, Fischer, SB, Reinbold, CS, Kittel-Schneider, S, Fullerton, JM, Oruc, L, Para, JG, Mayoral, F, Rivas, F, Czerski, PM, Kammerer-Ciernioch, J, Vedder, H, Borrmann-Hassenbach, M, Pfennig, A, Brennan, P, McKay, JD, Kogevinas, M, Schwarz, M, Schofield, PR, Muehleisen, TW, Schumacher, J, Bauer, M, Wright, A, Mitchell, PB, Hautzinger, M, Kelsoe, JR, Greenwood, TA, Nievergelt, CM, Shilling, PD, Smith, EN, Bloss, CS, Edenberg, HJ, Koller, DL, Gershon, ES, Liu, C, Badner, JA, Scheftner, WA, Lawson, WB, Nwulia, EA, Hipolito, M, Coryell, W, Rice, J, Byerley, W, McMahon, FJ, Lohoff, FW, Zandi, PP, Mahon, PB, McInnis, MG, Zollner, S, Zhang, P, Szelinger, S, St Clair, D, Caesar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Kirov, G, Nikolov, I, Collier, DA, Elkin, A, Williamson, R, Young, AH, Ferrier, IN, Milanova, V, Alda, M, Cervantes, P, Cruceanu, C, Rouleau, GA, Turecki, G, Paciga, S, Winslow, AR, Grigoroiu-Serbanescu, M, Ophoff, R, Adolfsson, R, Adolfsson, AN, Del-Favero, J, Pato, C, Biernacka, JM, Frye, MA, Morris, D, Schork, NJ, Reif, A, Lissowska, J, Hauser, J, Szeszenia-Dabrowska, N, McGhee, K, Quinn, E, Moskvina, V, Holmans, PA, Farmer, A, Kennedy, JL, Andreassen, OA, Mattingsdal, M, Bass, NJ, Gurling, H, McQuillin, A, Breuer, R, Hultman, C, Lichtenstein, P, Huckins, LM, Leboyer, M, Lathrop, M, Nurnberger, J, Steffens, M, Foroud, TM, Berrettini, WH, Craig, DW, and Shi, J

Abstract

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

Published
2018

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