Author: "Giegling, I" - Searchworks@Jio Institute Digital Library Search Results

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151. 5-HT2A RS643627 and RS594242 polymorphisms and personality traits

Author: Calati, R, Rujescu, D, Giegling, I, Mandelli, L, Schneider, B, Hartmann, A, Schnabel, A, Maurer, K, Moller, H, De Ronchi, D, Serretti, A, Calati R, Rujescu D, Giegling I, Mandelli L, Schneider B, Hartmann AM, Schnabel A, Maurer K, Moller HJ, De Ronchi D, Serretti A, Calati, R, Rujescu, D, Giegling, I, Mandelli, L, Schneider, B, Hartmann, A, Schnabel, A, Maurer, K, Moller, H, De Ronchi, D, Serretti, A, Calati R, Rujescu D, Giegling I, Mandelli L, Schneider B, Hartmann AM, Schnabel A, Maurer K, Moller HJ, De Ronchi D, and Serretti A
Published: 2006

152. 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

153. 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

154. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author: van den Berg, S.M., de Moor, M.H.M., McGue, M., Pettersson, E., Terracciano, A., Verweij, C.J.H., Amin, N., Derringer, J., Esko, T., Grootheest, G., Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., de Geus, E.J.C., Giegling, I., Gow, A. J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J., Jokela, M, Kiemeney, L., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Pulkki-Råback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J, Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Räikkönen, K., Arias-Vasquez, A., Costa, P.T., Keltikangas-Järvinen, L., van Duijn, C.M., Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Biological Psychology, Clinical Child and Family Studies, EMGO+ - Mental Health, Psychiatry, and EMGO - Mental health
Subjects: Netherlands Twin Register (NTR)
Abstract: Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized. © 2014 The Author(s).
Published: 2014

155. Serotonin receptor 1A and 2C SNPs and personality traits in suicide attempters and controls

Author: Calati R, Serretti A, Giegling I, Hartmann AM, Möller HJ, Rujescu D, Calati, R, Serretti, A, Giegling, I, Hartmann, A, Möller, H, and Rujescu, D
Subjects: HTR1A, HTR2C, TCI, Personality, Temperament, Character, Suicide
Published: 2008

156. Do the estrogens receptors 1 and 2 influence the Temperament and Character Inventory scores in suicidal attempters and healthy subjects?

Author: Chiesa A, Giegling I, Calati R, Hartmann AM, De Ronchi D, Serretti A, Rujescu D, Chiesa, A, Giegling, I, Calati, R, Hartmann, A, De Ronchi, D, Serretti, A, and Rujescu, D
Subjects: Estrogens, temperament, character, suicide attempters
Published: 2008

157. Do the estrogen receptors 1 gene variants influence the Temperament and Character Inventory scores in suicidal attempters and healthy subjects?

Author: Chiesa A, Giegling I, Calati R, Hartmann AM, De Ronchi D, Serretti A, Rujescu D, Chiesa, A, Giegling, I, Calati, R, Hartmann, A, De Ronchi, D, Serretti, A, and Rujescu, D
Subjects: Genetics, temperament, character, suicide
Published: 2008

158. I polimorfismi rs643627, 594242, rs6311 e rs6313 del gene 5-HT2A e i tratti di personalità

Author: Serretti A, Calati R, Giegling I, Hartmann AM, Moller HJ, Colombo C, Rujescu D, Serretti, A, Calati, R, Giegling, I, Hartmann, A, Moller, H, Colombo, C, and Rujescu, D
Subjects: Genetics, serotonin, personality
Published: 2008

159. Temperamento e carattere in soggetti con tentato suicidio e in soggetti sani

Author: Calati R, Rujescu D, Mandelli L, Giegling I, Schneider B, Hartmann AM, Schnabel A, Maurer K, Moller HJ, De Ronchi D, Serretti A, Calati, R, Rujescu, D, Mandelli, L, Giegling, I, Schneider, B, Hartmann, A, Schnabel, A, Maurer, K, Moller, H, De Ronchi, D, and Serretti, A
Subjects: Temperamento, carattere, suicidio
Published: 2008

160. Temperamento e carattere in soggetti con tentato suicidio e in soggetti sani

Author: Calati R, Rujescu DLM, Giegling I, Schneider B, Hartmann AM, Schnabel A, Maurer K, Moller HJ, De Ronchi D, Serretti A, Calati, R, Rujescu, D, Giegling, I, Schneider, B, Hartmann, A, Schnabel, A, Maurer, K, Moller, H, De Ronchi, D, and Serretti, A
Subjects: Temperament, character, suicide
Published: 2007

161. 5-HT2A and COMT SNPs and the Temperament and Character Inventory

Author: Calati R, Giegling I, Serretti A, Hartmann AM, Möller HJ, Rujescu D, Calati, R, Giegling, I, Serretti, A, Hartmann, A, Möller, H, and Rujescu, D
Subjects: Serotonin, COMT, temperament, character, personality, suicide
Published: 2007

162. Polimorfismi rs643627, rs594242, rs6311 e rs6313 del gene del 5-HT2A e tratti di personalità

Author: Serretti A, Calati R, Giegling I, Hartmann AM, Moller HJ, Rujescu D, Serretti, A, Calati, R, Giegling, I, Hartmann, A, Moller, H, and Rujescu, D
Subjects: Polimorfismi, genetica, serotonina, personalità
Published: 2007

163. 5-HT2A RS643627 and RS594242 polymorphisms and personality traits

Author: Calati R, Rujescu D, Giegling I, Mandelli L, Schneider B, Hartmann AM, Schnabel A, Maurer K, Moller HJ, De Ronchi D, Serretti A, Calati, R, Rujescu, D, Giegling, I, Mandelli, L, Schneider, B, Hartmann, A, Schnabel, A, Maurer, K, Moller, H, De Ronchi, D, and Serretti, A
Subjects: Character, TCI, 5-HT2A, Temperament, Personality
Published: 2006

164. The analysis of specific copy number variants (CNVs) in patient-derived neural and glial cells

Author: Jung, M., primary, Schiller, J., additional, Torenz, J., additional, Gies, A., additional, Klemenz, A., additional, Hartmann, A., additional, Giegling, I., additional, and Rujescu, D., additional
Published: 2016
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165. Nine differentially expressed genes from a post mortem study and their association with suicidal status in a sample of suicide completers, attempters and controls

Author: Balestri, M., primary, Crisafulli, C., additional, Donato, L., additional, Giegling, I., additional, Calati, R., additional, Antypa, N., additional, Schneider, B., additional, Marusic, D., additional, Tarozzi, M.E., additional, Paragi, M., additional, Hartmann, A.M., additional, Konte, B., additional, Marsano, A., additional, Serretti, A., additional, and Rujescu, D., additional
Published: 2016
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166. The analysis of neurodevelopmental disorders by the generation of 3D cerebral organoids mimicking the human cerebral development

Author: Jung, M., primary, Schiller, J., additional, Gimpel, A.S., additional, Hartmann, A., additional, Giegling, I., additional, and Rujescu, D., additional
Published: 2016
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167. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways.

Author: O'Dushlaine, C., Rossin, L., Lee, P.H., Duncan, L., Parikshak, N.N., Newhouse, S., Ripke, S., Neale, B.M., Purcell, S., Posthuma, D., Nurnberger, J.I., Lee, S.H., Faraone, S.V., Perlis, R.H., Mowry, B.J., Thapar, A., Goddard, M.E., Witte, J.S., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen, O.A., Anjorin, A., Anney, R., Anttila, V., Arking, D.E., Asherson, P., Azevedo, M.H., Backlund, L., Badner, J.A., Bailey, A.J., Banaschewski, T., Barchas, J.D., Barnes, M.R., Barrett, T.B., Bass, N., Battaglia, A., Bauer, M., Bayes, M., Bellivier, F., Bergen, S.E., Berrettini, W., Betancur, C., Bettecken, T., Biederman, J., Binder, E.B., Black, D.W., Blackwood, D.H., Bloss, C.S., Boehnke, M., Boomsma, D.I., Breuer, R., Bruggeman, R., Cormican, P., Buccola, N.G., Buitelaar, J.K., Bunney, W.E., Buxbaum, J.D., Byerley, W.F., Byrne, E.M., Caesar, S., Cahn, W., Cantor, R.M., Casas, M., Chakravarti, A., Chambert, K., Choudhury, K., Cichon, S., Mattheisen, M., Cloninger, C.R., Collier, D.A., Cook, E.H., Coon, H., Cormand, B., Corvin, A., Coryell, W.H., Craig, D.W., Craig, I., Crosbie, J., Cuccaro, M.L., Curtis, D., Czamara, D., Datta, S., Dawson, G., Day, R., Geus, E.J. de, Degenhardt, F., Djurovic, S., Donohoe, G., Doyle, A., Duan, J., Dudbridge, F., Duketis, E., Ebstein, R.P., Edenberg, H.J., Elia, J., Ennis, S., Etain, B., Fanous, A., Farmer, A., Ferrier, I.N., Flickinger, M., Foroud, T.M., Frank, J., Franke, B., Fraser, C., Freedman, R., Freimer, N.B., Freitag, C.M., Friedl, M., Frisen, L., Gallagher, L., Gejman, P.V., Georgieva, L., Gershon, E.S., Giegling, I., Gill, M., Gordon, S., Gordon-Smith, K., Green, E.K., Greenwood, T.A., Grice, D.E., Gross, M., Grozeva, D., Guan, W., Gurling, H., Haan, L. de, Haines, J.L., Hakonarson, H., Hallmayer, J., Hamilton, S.P., Hamshere, M., Hansen, T., Hartmann, A.M., Hauutzinger, M., Heath, A.C., Henders, A.K., Herms, S., Hickie, I., et al., O'Dushlaine, C., Rossin, L., Lee, P.H., Duncan, L., Parikshak, N.N., Newhouse, S., Ripke, S., Neale, B.M., Purcell, S., Posthuma, D., Nurnberger, J.I., Lee, S.H., Faraone, S.V., Perlis, R.H., Mowry, B.J., Thapar, A., Goddard, M.E., Witte, J.S., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen, O.A., Anjorin, A., Anney, R., Anttila, V., Arking, D.E., Asherson, P., Azevedo, M.H., Backlund, L., Badner, J.A., Bailey, A.J., Banaschewski, T., Barchas, J.D., Barnes, M.R., Barrett, T.B., Bass, N., Battaglia, A., Bauer, M., Bayes, M., Bellivier, F., Bergen, S.E., Berrettini, W., Betancur, C., Bettecken, T., Biederman, J., Binder, E.B., Black, D.W., Blackwood, D.H., Bloss, C.S., Boehnke, M., Boomsma, D.I., Breuer, R., Bruggeman, R., Cormican, P., Buccola, N.G., Buitelaar, J.K., Bunney, W.E., Buxbaum, J.D., Byerley, W.F., Byrne, E.M., Caesar, S., Cahn, W., Cantor, R.M., Casas, M., Chakravarti, A., Chambert, K., Choudhury, K., Cichon, S., Mattheisen, M., Cloninger, C.R., Collier, D.A., Cook, E.H., Coon, H., Cormand, B., Corvin, A., Coryell, W.H., Craig, D.W., Craig, I., Crosbie, J., Cuccaro, M.L., Curtis, D., Czamara, D., Datta, S., Dawson, G., Day, R., Geus, E.J. de, Degenhardt, F., Djurovic, S., Donohoe, G., Doyle, A., Duan, J., Dudbridge, F., Duketis, E., Ebstein, R.P., Edenberg, H.J., Elia, J., Ennis, S., Etain, B., Fanous, A., Farmer, A., Ferrier, I.N., Flickinger, M., Foroud, T.M., Frank, J., Franke, B., Fraser, C., Freedman, R., Freimer, N.B., Freitag, C.M., Friedl, M., Frisen, L., Gallagher, L., Gejman, P.V., Georgieva, L., Gershon, E.S., Giegling, I., Gill, M., Gordon, S., Gordon-Smith, K., Green, E.K., Greenwood, T.A., Grice, D.E., Gross, M., Grozeva, D., Guan, W., Gurling, H., Haan, L. de, Haines, J.L., Hakonarson, H., Hallmayer, J., Hamilton, S.P., Hamshere, M., Hansen, T., Hartmann, A.M., Hauutzinger, M., Heath, A.C., Henders, A.K., Herms, S., Hickie, I., and et al.
Abstract: Contains fulltext : 153763pre.pdf (preprint version ) (Open Access)
Published: 2015

168. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Author: Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., et al., Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., and et al.
Abstract: Contains fulltext : 153372.pdf (publisher's version ) (Closed access), IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism.
Published: 2015

169. Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

Author: Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
Abstract: IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15%of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P <.05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identi
Published: 2015
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170. All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs

Author: Aj, Schork, Wk, Thompson, Pham P, Torkamani A, Jc, Roddey, Pf, Sullivan, Jr, Kelsoe, Donovan Mc, O., Furberg H, Tobacco and Genetics Consortium, Bipolar Disorder Psychiatric Genomics Consortium, Schizophrenia Psychiatric Genomics Consortium, Nj, Schork, Oa, Andreassen, Am, Dale, Absher D, Agudo A, Almgren P, Ardissino D, Tl, Assimes, Bandinelli S, Barzan L, Bencko V, Benhamou S, Ej, Benjamin, Bernardinelli L, Bis J, Boehnke M, Boerwinkle E, Di, Boomsma, Brennan P, Canova C, Castellsagué X, Chanock S, Chasman D, Di, Conway, Dackor J, Ej, Geus, Duan J, Elosua R, Everett B, Fabianova E, Ferrucci L, Foretova L, Sp, Fortmann, Franceschini N, Frayling T, Furberg C, Pv, Gejman, Groop L, Gu F, Guralnik J, Se, Hankinson, Haritunians T, Healy C, Hofman A, Holcátová I, Dj, Hunter, Sj, Hwang, Jp, Ioannidis, Iribarren C, Au, Jackson, Janout V, Kaprio J, Kim Y, Kjaerheim K, Jw, Knowles, Kraft P, Ladenvall C, Lagiou P, Lanthrop M, Lerman C, Df, Levinson, Levy D, Md, Li, Dy, Lin, Eh, Lips, Lissowska J, Lowry R, Lucas G, Tv, Macfarlane, Maes H, Pm, Mannucci, Mates D, Mauri F, Ja, Mcgovern, Jd, Mckay, McKnight B, Melander O, Pa, Merlini, Milaneschi Y, Kl, Mohlke, Donnell Cj, O., Pare G, Bw, Penninx, Perry J, Posthuma D, Sr, Preis, Psaty B, Quertermous T, Vs, Ramachandran, Richiardi L, Ridker P, Rose J, Rudnai P, Salomaa V, Ar, Sanders, Sm, Schwartz, Shi J, Jh, Smit, Hm, Stringham, Szeszenia-Dabrowska N, Tanaka T, Taylor K, Thacker E, Thornton L, Tiemeier H, Tuomilehto J, Ag, Uitterlinden, Cm, Duijn, Jm, Vink, Vogelzangs N, Bf, Voight, Walter S, Willemsen G, Zaridze D, Znaor A, Akil H, Anjorin A, Backlund L, Ja, Badner, Jd, Barchas, Tb, Barrett, Bass N, Bauer M, Bellivier F, Se, Bergen, Berrettini W, Blackwood D, Cs, Bloss, Breen G, Breuer R, We, Bunner, Burmeister M, Byerley W, Caesar S, Chambert K, Cichon S, St Clair D, Da, Collier, Corvin A, Wh, Coryell, Craddock N, Dw, Craig, Daly M, Day R, Degenhardt F, Djurovic S, Dudbridge F, Hj, Edenberg, Elkin A, Etain B, Ae, Farmer, Ma, Ferreira, Ferrier I, Flickinger M, Foroud T, Frank J, Fraser C, Frisén L, Es, Gershon, Gill M, Gordon-Smith K, Ek, Green, Ta, Greenwood, Grozeva D, Guan W, Gurling H, Ó, Gustafsson, Ml, Hamshere, Hautzinger M, Herms S, Hipolito M, Pa, Holmans, Cm, Hultman, Jamain S, Eg, Jones, Jones I, Jones L, Kandaswamy R, Jl, Kennedy, Gk, Kirov, Dl, Koller, Kwan P, Landén M, Langstrom N, Lathrop M, Lawrence J, Wb, Lawson, Leboyer M, Ph, Lee, Li J, Lichtenstein P, Lin D, Liu C, Fw, Lohoff, Lucae S, Pb, Mahon, Maier W, Ng, Martin, Mattheisen M, Matthews K, Mattingsdal M, Ka, Mcghee, McGuffin P, Mg, Mcinnis, McIntosh A, McKinney R, Aw, Mclean, Fj, Mcmahon, McQuillin A, Meier S, Melle I, Meng F, Pb, Mitchell, Gw, Montgomery, Moran J, Morken G, Dw, Morris, Moskvina V, Muglia P, Tw, Mühleisen, Wj, Muir, Müller-Myhsok B, Rm, Myers, Cm, Nievergelt, Nikolov I, Nimgaonkar V, Mm, Nöthen, Ji, Nurnberger, Ea, Nwulia, O'Dushlaine C, Osby U, Óskarsson H, Mj, Owen, Petursson H, Bs, Pickard, Porgeirsson P, Jb, Potash, Propping P, Sm, Purcell, Quinn E, Raychaudhuri S, Rice J, Rietschel M, Ruderfer D, Schalling M, Af, Schatzberg, Wa, Scheftner, Pr, Schofield, Tg, Schulze, Schumacher J, Mm, Schwarz, Scolnick E, Lj, Scott, Pd, Shilling, Sigurdsson E, Sklar P, En, Smith, Stefansson H, Stefansson K, Steffens M, Steinberg S, Strauss J, Strohmaier J, Szelinger S, Rc, Thompson, Tozzi F, Treutlein J, Jb, Vincent, Sj, Watson, Tf, Wienker, Williamson R, Sh, Witt, Wright A, Xu W, Ah, Young, Pp, Zandi, Zhang P, Zöllner S, Agartz I, Albus M, Alexander M, Rl, Amdur, Amin F, Bitter I, Dw, Black, Ad, Børglum, Ma, Brown, Bruggeman R, Ng, Buccola, Wf, Byerley, Cahn W, Rm, Cantor, Vj, Carr, Sv, Catts, Choudhury K, Cloninger C, Cormican P, Pa, Danoy, Datta S, DeHert M, Demontis D, Dikeos D, Donnelly P, Donohoe G, Duong L, Dwyer S, Fanous A, Fink-Jensen A, Freedman R, Nb, Freimer, Friedl M, Georgieva L, Giegling I, Glenthøj B, Godard S, Golimbet V, de Haan L, Hansen M, Hansen T, Am, Hartmann, Fa, Henskens, Dm, Hougaard, Ingason A, Av, Jablensky, Kd, Jakobsen, Jay M, Eg, Jönsson, Jürgens G, Rs, Kahn, Mc, Keller, Ks, Kendler, Kenis G, Kenny E, Konnerth H, Konte B, Krabbendam L, Krasucki R, Vk, Lasseter, Laurent C, Lencz T, Lerer F, Ky, Liang, Ja, Lieberman, Dh, Linszen, Lönnqvist J, Cm, Loughland, Aw, Maclean, Bs, Maher, Ak, Malhotra, Mallet J, Malloy P, Jj, Mcgrath, McLean DE, Pt, Michie, Milanova V, Mors O, Pb, Mortensen, Bj, Mowry, Myin-Germeys I, Neale B, Da, Nertney, Nestadt G, Nielsen J, Nordentoft M, Norton N, O'Neill F, Olincy A, Olsen L, Ra, Ophoff, Tf, Ørntoft, van Os J, Pantelis C, Papadimitriou G, Cn, Pato, Mt, Pato, Peltonen L, Pickard B, Op, Pietiläinen, Pimm J, Ae, Pulver, Puri V, Digby Quested, Hb, Rasmussen, Jm, Réthelyi, Ribble R, Bp, Riley, Rossin L, Ruggeri M, Rujescu D, Schall U, Sg, Schwab, Rj, Scott, Jm, Silverman, Cc, Spencer, Strange A, Strengman E, Stroup T, Suvisaari J, Terenius L, Thirumalai S, Timm S, Toncheva D, Tosato S, Ej, Den Oord, Veldink J, Pm, Visscher, Walsh D, Ag, Wang, Werge T, Wiersma D, Db, Wildenauer, Hj, Williams, Nm, Williams, van Winkel R, Wormley B., Biological Psychology, Functional Genomics, Educational Neuroscience, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, Biophotonics and Medical Imaging, LEARN! - Brain, learning and development, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, LaserLaB - Biophotonics and Microscopy, ANS - Amsterdam Neuroscience, Adult Psychiatry, Psychiatry, Human genetics, Epidemiology and Data Science, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Gibson, Greg, Germeys, Inez, van Winkel, Ruud, and De Hert, Marc
Subjects: False discovery rate, Netherlands Twin Register (NTR), Cancer Research, Linkage disequilibrium, Genome-wide association study, Linkage Disequilibrium, 0302 clinical medicine, 2.1 Biological and endogenous factors, Aetiology, Genetics (clinical), Genetics, 0303 health sciences, Statistics, Genomics, Single Nucleotide, Genome Scans, Tobacco and Genetics Consortium, Functional Genomics, Phenotype, complex trait, Research Article, Bipolar Disorder Psychiatric Genomics Consortium, lcsh:QH426-470, SNP, Single-nucleotide polymorphism, Computational biology, Biostatistics, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, "genome-wide association study", Genome Analysis Tools, Clinical Research, Schizophrenia Psychiatric Genomics Consortium, Genome-Wide Association Studies, Humans, Genetic Predisposition to Disease, Statistical Methods, Polymorphism, Molecular Biology, Genetic Association Studies, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, Linkage (software), Human Genome, Computational Biology, Human Genetics, Heritability, R1, schizophrenia, lcsh:Genetics, Schizophrenia, Mathematics, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology
Abstract: Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1−FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci., Author Summary Modern genome-wide association studies (GWAS) have failed to identify large portions of the genetic basis of common, complex traits. Recent work suggested this could be because many genetic variants, each with individually small effects, compose their genetic architecture, limiting the power of GWAS. Moreover, these variants appear more abundantly in and near genes. Using genome annotations, summary statistics from several of the largest GWAS, and established statistical methods for quantifying distributions of test statistics, we show a consistency across studies. Namely, we show that, across all assessed traits, the test statistics resulting from SNPs that are related to the 5′ UTR of genes show the largest abundance of associations, while SNPs related to exons and the 3′UTR are also enriched. SNPs related to introns are only moderately enriched, and intergenic SNPs show a depletion of associations relative to the average SNP. This enrichment corresponds directly to increased replication across independent samples and can be incorporated a priori into statistical methods to improve discovery and prediction. Our results contribute to on-going debates about the functional nature of the genetic architecture of complex traits and point to avenues for leveraging existing GWAS data for discovery in future GWA and sequencing studies.
Published: 2013

171. Identification of risk loci with shared effects on five major psychiatric disorders:a genome-wide analysis

Author: Smoller, J.W., Ripke, S., Lee, P.H., Neale, B., Nurnberger, J.I., Santangelo, S., Sullivan, P.F., Perlis, R.H., Purcell, S.M., Fanous, A., Neale, M.C., Rietschel, M., Schulze, T.G., Thapar, A., Anney, R., Buitelaar, J.K., Farone, S.V., Hoogendijk, W.J.G., Levinson, D.F., Lesch, K.P., Riley, B., Schachar, R., Sonuga-Barke, E.J., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen, O.A., Anjorin, A., Arking, D., Asherson, P., Azevedo, M.H., Backlund, L., Badner, J.A., Banaschewski, T., Barchas, J.D., Barnes, M.R., Bass, N., Bauer, M.C.R., Bellivier, F., Bergen, S.E., Berrettini, W., Bettecken, T., Biederman, J, Binder, E.B., Black, D.W., Blackwood, D.H., Bloss, C.S., Boehnke, M., Boomsma, D.I., Breen, G., Breuer, R., Buccola, N.G., Bunner, W.E., Burmeister, M., Buxbaum, J.D., Byerley, W. F., Sian, C., Cantor, R.M., Chakravarti, A., Chambert, K., Chicon, S., Cloniger, C.R., Collier, D.A., Cook, E., Coon, H., Corvin, A., Coryell, W.H., Craig, D.W., Craig, I.W., Curtis, D., Czamara, D., Daly, M., Datta, S., Day, R., de Geus, E.J.C., Degenhardt, F., Devlin, B., Srdjan, D., Doyle, A.E., Duan, J., Dudbridge, F., Edenberg, H.J., Elkin, A., Etain, B., Farmer, A.E., Ferreira, M.A.R., Ferrier, I.N., Flickinger, M., Foroud, T., Frank, J., Franke, B., Fraser, C., Freedman, R., Freimer, N.B., Friedl, M., Frisén, L., Gejman, P.V., Georgieva, L., Gershon, E.S., Giegling, I., Gill, M., Gordon, S.D., Gordon-Smith, K., Green, E.K., Greenwood, T.A., Gross, M., Grozeva, D., Guan, W., Gurling, H., Gustafsson, O., Hakonarson, H., Hamilton, S.P., Hamshere, M.L., Hansen, T.F., Hartmann, A.M., Hautzinger, M., Heath, A.C., Henders, A.K., Herms, S., Hickie, I.B., Hipolito, M., Hoefels, S., Holmans, P.A., Holsboer, F., Hottenga, J.J., Hultman, C. M., Ingason, A., Ising, M., Jamain, S., Jones, E.G., Jones, L., Jones, I., Jung-Ying, T., Kahler, A., Kandaswamy, R., Keller, M.C., Kelsoe, J., Kennedy, J.L., Kenny, E., Kim, Y., Kirov, G. K., Knowles, J.A., Kohli, M.A., Koller, D.L., Konte, B., Korszun, A., Krasucki, R., Kuntsi, J., Phoenix, K., Landén, M., Langstrom, N., Lathrop, M., Lawrence, J., Lawson, W.B., Leboyer, M., Lencz, T., Lewis, C.M., Li, J., Lichtenstein, P., Lieberman, J. A., Lin, D., Liu, C., Lohoff, F.W., Loo, S.K., Lucae, S., MacIntyre, D.J., Madden, P.A.F., Magnusson, P., Mahon, P.B., Maier, W., Malhotra, A.K., Mattheisen, M., Matthews, K., Mattingsdal, M., McCarroll, S., McGhee, K.A., McGough, J.J., McGrath, P.J., McGuffin, P., McInnis, M.G., McIntosh, A., McKinney, R., McClean, A.W., McMahon, F.J., McQuillin, A., Medeiros, H., Medland, S.E., Meier, S., Melle, I., Meng, F., Middeldorp, C.M., Middleton, L., Vihra, M., Mitchell, P.B., Montgomery, G.W., Moran, J., Morken, G., Morris, D.W., Moskvina, V., Mowry, B. J., Muglia, P., Mühleisen, T.W., Muir, W.J., Müller-Myhsok, B., Myers, R.M., Nelson, S.F., Nievergelt, C.M., Nikolovq, I., Nimgaonkar, V.L., Nolen, W.A., Nöthen, M.M., Nwulia, E.A., Nyholt, DR, O'Donovan, M.C., O'Dushlaine, C., Oades, R.D., Olincy, A., Olsen, L., Ophoff, R.A., Osby, U., Óskarsson, H., Owen, M.J., Palotie, A., Pato, M.T., Pato, C.N., Penninx, B.W.J.H., Pergadia, M.L., Petursson, H., Pickard, B.S., Pimm, J., Piven, J., Porgeirsson, P., Posthuma, D., Potash, J.B., Propping, J., Puri, V., Quested, D., Quinn, E.M., Rasmussen, H.B., Raychaudhuri, S., Rehnström, K., Reif, A., Rice, J., Rossin, L., Rothenberger, A., Rouleau, G., Ruderfer, D., Rujescu, D., Sanders, A.R., Schalling, M., Schatzberg, A.F., Scheftner, W.A., Schellenberg, G.D., Schofield, P.R., Schork, N.J., Schumacher, J., Schwarz, M.M., Scolnick, E., Scott, L.J., Shi, J., Shillling, P.D., Shyn, S.I., Sigurdsson, E., Silverman, J.M., Sklar, P., Slager, S.L., Smalley, S.L., Smit, J.H., Smith, E.N., Sonuga-Barke, E., St Clair, D., State, M., Stefansson, K., Stefansson, H., Steffans, M., Steinberg, S., Steinhausen, H.C., Strauss, J., Strohmaier, J., Stroup, T.S., Sutcliffe, J., Szatmari, P., Szelinger, S., Thirumalai, S., Thompson, R.C., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Grootheest, G., Vieland, V., Vincent, J.B., Visscher, P.M., Watson, S.J., Weissman, M.M., Werge, T., Wienker, T.F., Willemsen, G., Williamson, R., Witt, S.H., Wray, N.R., Wright, A., Xu, W., Young, A.H., Zammit, S., Zandi, P.P., Zhang, P., Zitman, F.G., Zöllner, S., Kendler, K.S., Psychiatry, Human genetics, Epidemiology and Data Science, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Oades, Robert D. (Beitragende*r), and Oades, Robert D.
Subjects: Netherlands Twin Register (NTR), Adult, medicine.medical_specialty, Bipolar Disorder, Calcium Channels, L-Type, Population, Medizin, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], medicine, ddc:61, Attention deficit hyperactivity disorder, Humans, DCN PAC - Perception action and control NCEBP 9 - Mental health, ddc:610, Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Bipolar disorder, Age of Onset, Psychiatry, education, Child, Genetics, education.field_of_study, Depressive Disorder, Major, General Medicine, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], medicine.disease, Logistic Models, Autism spectrum disorder, Schizophrenia, Attention Deficit Disorder with Hyperactivity, Child Development Disorders, Pervasive, Genetic Loci, Expression quantitative trait loci, Major depressive disorder, Genome-Wide Association Study
Abstract: Item does not contain fulltext BACKGROUND: Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. METHODS: We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. FINDINGS: SNPs at four loci surpassed the cutoff for genome-wide significance (p
Published: 2013

172. Duplications in RB1CC1 are associated with schizophrenia; identification in large European sample sets

Author: Degenhardt, F., Priebe, L., Nenadic, I., Sauer, H., Mattheisen, M., Buizer-Voskamp, J., Ophoff, R. A., Consortium, GROUP, Rujescu, D., Giegling, I., Ingason, A., Wagner, M., Meier, S., Delobel, B., Andrieux, J., Meyer-Lindenberg, A., Heinz, A., Walter, H., Moebus, S., Corvin, A., Wellcome Trust Case Control Consortium 2, International Schizophrenia Consortium, Rietschel, M., Nöthen, M. M., Lennertz, L., Cichon, S., Kahn, René S, Linszen, Don H, van Os, Jim, Wiersma, Durk, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Krabbendam, Lydia, Myin-Germeys, Inez, Streit, F., Witt, S. H., Hofmann, A., Becker, T., Mössner, R., Maier, W., Germeys, Inez, Adult Psychiatry, and ANS - Amsterdam Neuroscience
Subjects: Adult, Male, Candidate gene, Medizin, Autophagy-Related Proteins, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Polymorphism (computer science), Gene Duplication, Gene duplication, genetics [Protein-Tyrosine Kinases], Medicine, Humans, Genetic Predisposition to Disease, genetics [Schizophrenia], DGCR2, Copy-number variation, ddc:610, genetics [Genetic Predisposition to Disease], Gene, Biological Psychiatry, Exome sequencing, 030304 developmental biology, Aged, Genetics, 0303 health sciences, business.industry, genetics [Gene Duplication], RB1-inducible coiled-coil 1, Odds ratio, Middle Aged, Protein-Tyrosine Kinases, exome-sequencing, schizoaffective disorder, 3. Good health, Europe, Psychiatry and Mental health, intellectual disability, RB1CC1 protein, human, Behavioral medicine, Schizophrenia, Original Article, Female, business, 030217 neurology & neurosurgery
Abstract: Schizophrenia (SCZ) is a severe and debilitating neuropsychiatric disorder with an estimated heritability of ~80%. Recently, de novo mutations, identified by next-generation sequencing (NGS) technology, have been suggested to contribute to the risk of developing SCZ. Although these studies show an overall excess of de novo mutations among patients compared with controls, it is not easy to pinpoint specific genes hit by de novo mutations as actually involved in the disease process. Importantly, support for a specific gene can be provided by the identification of additional alterations in several independent patients. We took advantage of existing genome-wide single-nucleotide polymorphism data sets to screen for deletions or duplications (copy number variations, CNVs) in genes previously implicated by NGS studies. Our approach was based on the observation that CNVs constitute part of the mutational spectrum in many human disease-associated genes. In a discovery step, we investigated whether CNVs in 55 candidate genes, suggested from NGS studies, were more frequent among 1637 patients compared with 1627 controls. Duplications in RB1CC1 were overrepresented among patients. This finding was followed-up in large, independent European sample sets. In the combined analysis, totaling 8461 patients and 112 871 controls, duplications in RB1CC1 were found to be associated with SCZ (P=1.29 × 10(-5); odds ratio=8.58). Our study provides evidence for rare duplications in RB1CC1 as a risk factor for SCZ. ispartof: Translational Psychiatry vol:3 issue:11 ispartof: location:United States status: published
Published: 2013

173. Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach

Author: Völter, C, Riedel, M, Aichert, D S, Lobo, S, Costa, A, Schmechtig, A, Collier, D A, Hartmann, A M, Giegling, I, Möller, H J, Quednow, Boris B, Rujescu, D, Kumari, V, Ettinger, U, University of Zurich, and Ettinger, U
Subjects: 2738 Psychiatry and Mental Health, 3004 Pharmacology, 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, 10076 Center for Integrative Human Physiology, 570 Life sciences, biology, 2736 Pharmacology (medical), 610 Medicine & health
Published: 2012

174. Variation within the Huntington's disease gene influences normal brain structure

Author: Mühlau, M., Winkelmann, J., Rujescu, D., Giegling, I., Koutsouleris, N., Gaser, C., Arsic, M., Weindl, A., Reiser, M., and Meisenzahl, E.M.
Subjects: mental disorders, cag repeats, basal ganglia, segmentation, inference, mutation, bipolar, images, onset, mri, age
Abstract: Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain.
Published: 2012

175. Die Zukunft der Suchtmedizin – ... hilft die Genetik weiter?

Author: Giegling I, G. Koller, Monika Ridinger, Ulrich W. Preuss, Norbert Wodarz, C Fehr, B Bondy, Peter Zill, Michael Soyka, and D Rujescu
Subjects: Psychiatry and Mental health, Applied Psychology
Published: 2011

176. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder

Author: Williams, H.J., Norton, N., Dwyer, S., Moskvina, V., Nikolov, I., Carroll, L., Georgieva, L., Williams, N.M., Morris, D.W., Quinn, E.M., Giegling, I., Ikeda, M., Wood, J., Lencz, T., Hultman, C., Lichtenstein, P., Thiselton, D., Maher, B.S., Malhotra, A.K., Riley, B., Kendler, K.S., Gill, M., Sullivan, P., Sklar, P., Purcell, S., Nimgaonkar, V.L., Kirov, G., Holmans, P., Corvin, A., Rujescu, D., Craddock, N., Owen, M.J., O'Donovan, M.C., GROUP investigators, [No Value], and Science in Healthy Ageing & healthcaRE (SHARE)
Subjects: mental disorders
Abstract: A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P = 1.61 x 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P = 9.96 x 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N = 18 945, schizophrenia plus bipolar disorder N = 21 274 and controls N = 38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P = 2.5 x 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P = 4.1 x 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder. Molecular Psychiatry (2011) 16, 429-441; doi:10.1038/mp.2010.36; published online 6 April 2010
Published: 2011

177. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder

Author: Sullivan, P, Lencz, T, Kendler, K S, Williams, H J, Corvin, A, Nimgaonkar, V L, Ikeda, M, Morris, D W, Nikolov, I, Purcell, S, Maher, B S, Norton, N, Wood, J, Sklar, P, Hultman, C, Moskvina, V, Gill, M, Thiselton, D, Quinn, E M, Kirov, G, Owen, M J, Riley, B, Malhotra, A K, Holmans, P, Giegling, I, Dwyer, S, Rujescu, D, Carroll, L, Lichtenstein, P, Craddock, N, Williams, N M, and Georgieva, L
Subjects: mental disorders
Abstract: A recent genome wide association study reported evidence for association between rs1344706 within ZNF804A (encoding zinc finger protein 804A) and schizophrenia (P=1.61 ×10−7), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 ×10−9). Here we provide additional evidence for association through meta-analysis of a larger dataset (schizophrenia/schizoaffective disorder N = 18945, schizophrenia plus bipolar disorder N =21274, controls N =38675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high density LD mapping. Meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 ×10−11, OR=1.10, 95% CI 1.07–1.14) and schizophrenia and bipolar disorder combined (P=4.1 ×10−13, OR=1.11, 95% CI 1.07–1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.
Published: 2011
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178. Genome-wide association study identifies five new schizophrenia loci

Author: Ripke, S. Sanders, A.R. Kendler, K.S. Levinson, D.F. Sklar, P. Holmans, P.A. Lin, D.-Y. Duan, J. Ophoff, R.A. Andreassen, O.A. Scolnick, E. Cichon, S. St. Clair, D. Corvin, A. Gurling, H. Werge, T. Rujescu, D. Blackwood, D.H.R. Pato, C.N. Malhotra, A.K. Purcell, S. Dudbridge, F. Neale, B.M. Rossin, L. Visscher, P.M. Posthuma, D. Ruderfer, D.M. Fanous, A. Stefansson, H. Steinberg, S. Mowry, B.J. Golimbet, V. De Hert, M. Jönsson, E.G. Bitter, I. Pietiläinen, O.P.H. Collier, D.A. Tosato, S. Agartz, I. Albus, M. Alexander, M. Amdur, R.L. Amin, F. Bass, N. Bergen, S.E. Black, D.W. Børglum, A.D. Brown, M.A. Bruggeman, R. Buccola, N.G. Byerley, W.F. Cahn, W. Cantor, R.M. Carr, V.J. Catts, S.V. Choudhury, K. Cloninger, C.R. Cormican, P. Craddock, N. Danoy, P.A. Datta, S. De Haan, L. Demontis, D. Dikeos, D. Djurovic, S. Donnelly, P. Donohoe, G. Duong, L. Dwyer, S. Fink-Jensen, A. Freedman, R. Freimer, N.B. Friedl, M. Georgieva, L. Giegling, I. Gill, M. Glenthøj, B. Godard, S. Hamshere, M. Hansen, M. Hansen, T. Hartmann, A.M. Henskens, F.A. Hougaard, D.M. Hultman, C.M. Ingason, A. Jablensky, A.V. Jakobsen, K.D. Jay, M. Jürgens, G. Kahn, R.S. Keller, M.C. Kenis, G. Kenny, E. Kim, Y. Kirov, G.K. Konnerth, H. Konte, B. Krabbendam, L. Krasucki, R. Lasseter, V.K. Laurent, C. Lawrence, J. Lencz, T. Lerer, F.B. Liang, K.-Y. Lichtenstein, P. Lieberman, J.A. Linszen, D.H. Lönnqvist, J. Loughland, C.M. MacLean, A.W. Maher, B.S. Maier, W. Mallet, J. Malloy, P. Mattheisen, M. Mattingsdal, M. McGhee, K.A. McGrath, J.J. McIntosh, A. McLean, D.E. McQuillin, A. Melle, I. Michie, P.T. Milanova, V. Morris, D.W. Mors, O. Mortensen, P.B. Moskvina, V. Muglia, P. Myin-Germeys, I. Nertney, D.A. Nestadt, G. Nielsen, J. Nikolov, I. Nordentoft, M. Norton, N. Nöthen, M.M. O'Dushlaine, C.T. Olincy, A. Olsen, L. O'Neill, F.A. Ørntoft, T.F. Owen, M.J. Pantelis, C. Papadimitriou, G. Pato, M.T. Peltonen, L. Petursson, H. Pickard, B. Pimm, J. Pulver, A.E. Puri, V. Quested, D. Quinn, E.M. Rasmussen, H.B. Réthelyi, J.M. Ribble, R. Rietschel, M. Riley, B.P. Ruggeri, M. Schall, U. Schulze, T.G. Schwab, S.G. Scott, R.J. Shi, J. Sigurdsson, E. Silverman, J.M. Spencer, C.C.A. Stefansson, K. Strange, A. Strengman, E. Stroup, T.S. Suvisaari, J. Terenius, L. Thirumalai, S. Thygesen, J.H. Timm, S. Toncheva, D. Van Den Oord, E. Van Os, J. Van Winkel, R. Veldink, J. Walsh, D. Wang, A.G. Wiersma, D. Wildenauer, D.B. Williams, H.J. Williams, N.M. Wormley, B. Zammit, S. Sullivan, P.F. O'Donovan, M.C. Daly, M.J. Gejman, P.V.
Abstract: We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10 -11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9). © 2011 Nature America, Inc. All rights reserved.
Published: 2011

179. Common variants at VRK2 and TCF4 conferring risk of schizophrenia

Author: Steinberg, S., Jong, S. d., Genomics, I. S., Andreassen, O. A., Werge, T., Børglum, A. D., Mors, O., Mortensen, P. B., Gustafsson, O., Costas, J., O. P. H., Demontis, D., Papiol, S., Huttenlocher, J., Mattheisen, M., Breuer, R., Vassos, E., Giegling, I., Fraser, G., Walker, N., Tuulio Henriksson, A., Suvisaari, J., Lönnqvist, J., Paunio, T., Agartz, I., Melle, I., Djurovic, S., Strengman, E., G. R. O., Jürgens, G., Glenthøj, B., Terenius, L., Hougaard, D. M., Orntoft, T., Wiuf, C., Didriksen, M., Hollegaard, M. V., Nordentoft, M., Winkel, R. v., Kenis, G., Abramova, L., Kaleda, V., Arrojo, M., Sanjuán, J., Arango, C., Sperling, S., Rossner, M., Ribolsi, M., Magni, V., Siracusano, A., Christiansen, C., Kiemeney, L. A., Veldink, J., Den, L. v., Ingason, A., Muglia, P., Murray, R., Nöthen, M. M., Sigurdsson, E., Petursson, H., Thorsteinsdottir, U., Kong, A., Rubino, I. A., Hert, M. D., Réthelyi, J. M., Bitter, I., Jönsson, E. G., Golimbet, V., Carracedo, A., Ehrenreich, H., Craddock, N., Owen, M. J., O'Donovan, M. C., Case, W. T., Ruggeri, Mirella, Tosato, Sarah, Peltonen, L., Ophoff, R. A., Collier, D. A., Clair, D. S., Rietschel, M., Cichon, S., Stefansson, H., Rujescu, D., Stefansson, K., Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Amsterdam Neuroscience, Adult Psychiatry, and deCODE Genetics, IS-101 Reykjavik, Iceland.
Subjects: schizophrenia, sequence variants, TCF4, Genome-wide association study, Transcription Factor 4, 0302 clinical medicine, VRK2 protein, human, Polymorphism (computer science), Genotype, genetics [Schizophrenia], Neurogranin, Genetics (clinical), Schizophrenia, Risk, Alleles, Polymorphism, Single Nucleotide, Transcription Factors, Humans, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Genetic Predisposition to Disease, Protein-Serine-Threonine Kinases, Genome-Wide Association Study, Genetics, 0303 health sciences, Association Studies Articles, Single Nucleotide, General Medicine, genetics [Transcription Factors], 3. Good health, Protein Serine-Threonine Kinases, Biology, genetics [Protein-Serine-Threonine Kinases], Molecular epidemiology [NCEBP 1], 03 medical and health sciences, ddc:570, Polymorphism, Allele, genetics [Basic Helix-Loop-Helix Leucine Zipper Transcription Factors], Settore MED/25 - Psichiatria, Molecular Biology, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 030304 developmental biology, Intron, Odds ratio, Molecular biology, TCF4 protein, human, 030217 neurology & neurosurgery
Abstract: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10(-9)] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10(-9)). European Union LSHM-CT-2006-037761 PIAP-GA-2008-218251 HEALTH-F2-2009-223423 National Genome Research Network of the German Federal Ministry of Education and Research (BMBF) 01GS08144 01GS08147 National Institute of Mental Health R01 MH078075 N01 MH900001 MH074027 Centre of Excellence for Complex Disease Genetics of the Academy of Finland 213506 129680 Biocentrum Helsinki Foundation Faculty of Medicine, University of Helsinki Stanley Medical Research Institute Danish Council for Strategic Research 2101-07-0059 H. Lundbeck A/S Research Council of Norway 163070/V50 South-East Norway Health Authority 2004-123 Medical Research Council Ministerio de Sanidad y Consumo, Spain PI081522 Xunta de Galicia 08CSA005208PR Swedish Research Council Wellcome Trust 083948/Z/07/Z Max Planck Society Eli Lilly and Company info:eu-repo/grantAgreement/EC/FP7/218251
Published: 2011

180. Genome-wide autozygosity is associated with lower general cognitive ability

Author: Howrigan, D P, primary, Simonson, M A, additional, Davies, G, additional, Harris, S E, additional, Tenesa, A, additional, Starr, J M, additional, Liewald, D C, additional, Deary, I J, additional, McRae, A, additional, Wright, M J, additional, Montgomery, G W, additional, Hansell, N, additional, Martin, N G, additional, Payton, A, additional, Horan, M, additional, Ollier, W E, additional, Abdellaoui, A, additional, Boomsma, D I, additional, DeRosse, P, additional, Knowles, E E M, additional, Glahn, D C, additional, Djurovic, S, additional, Melle, I, additional, Andreassen, O A, additional, Christoforou, A, additional, Steen, V M, additional, Hellard, S L, additional, Sundet, K, additional, Reinvang, I, additional, Espeseth, T, additional, Lundervold, A J, additional, Giegling, I, additional, Konte, B, additional, Hartmann, A M, additional, Rujescu, D, additional, Roussos, P, additional, Giakoumaki, S, additional, Burdick, K E, additional, Bitsios, P, additional, Donohoe, G, additional, Corley, R P, additional, Visscher, P M, additional, Pendleton, N, additional, Malhotra, A K, additional, Neale, B M, additional, Lencz, T, additional, and Keller, M C, additional
Published: 2015
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181. Fine mapping of ZNF804A and genome wide significant evidence for its involvement in schizophrenia and bipolar disorder

Author: Williams, H.J., Norton, N., Dwyer, S., Moskivina, V., Nikolov, I., Carroll, L., Georgieva, L., Williams, N.M., Morris, D.W., Quinn, E.M., Giegling, I., Ikeda, M., Wood, J., Lencz, T., Hultman, C., Lichtenstein, P., Thiselton, D., Mahler, B.S., Bruggeman, R., Cahn, W., de Haan, L., Kahn, R., Krabbendam, L., Linzen, D., Myin-Germeys, I., van Os, J, Wiersma, D., Malhotra, A.K., Riley, B., Kendler, K.S., Gill, M., Sklar, P., Purcell, S., Nimgaonkar, V.L., Kirov, G., Holmans, P., Corvin, A., Rujescu, D., Craddock, N., Educational Neuroscience, Clinical Child and Family Studies, LEARN! - Brain, learning and development, ANS - Amsterdam Neuroscience, Adult Psychiatry, Psychiatrie & Neuropsychologie, and RS: MHeNs School for Mental Health and Neuroscience
Subjects: Adult, Male, Linkage disequilibrium, Bipolar Disorder, Genotype, Quantitative Trait Loci, Kruppel-Like Transcription Factors, Schizoaffective disorder, Genome-wide association study, Locus (genetics), Bioinformatics, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Gene Frequency, Meta-Analysis as Topic, mental disorders, medicine, Odds Ratio, Humans, Genetic Predisposition to Disease, Bipolar disorder, Allele, Molecular Biology, 030304 developmental biology, Genetic association, Aged, Genetics, 0303 health sciences, biology, association, Chromosome Mapping, Exons, Middle Aged, medicine.disease, meta-analysis, Europe, Psychiatry and Mental health, biology.protein, Schizophrenia, Female, 030217 neurology & neurosurgery, Zinc finger protein 804A, ZNF804A, Genome-Wide Association Study
Abstract: A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 ? 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 ? 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N=18?945, schizophrenia plus bipolar disorder N=21?274 and controls N=38?675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 ? 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 ? 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.
Published: 2010

182. Enhanced calcium responses to serotonin receptor stimulation in T-lymphocytes from schizophrenic patients – A pilot study

Author: Genius, J., primary, Schellenberg, A., additional, Tchana-Duope, L., additional, Hartmann, N., additional, Giegling, I., additional, Hartmann, A., additional, Benninghoff, J., additional, and Rujescu, D., additional
Published: 2015
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183. How Can Pharmacogenomics Biomarkers Be Translated into Patient Benefit

Author: Collier, D., primary, Achilla, E., additional, Breen, G., additional, Curran, S., additional, Dima, D., additional, Flanagan, R., additional, Frank, J., additional, Frangou, S., additional, Gasse, C., additional, Giegling, I., additional, Rietschel, M., additional, Rujescu, D., additional, Maccabe, J., additional, McCrone, P., additional, Mill, J., additional, Sigurdsson, E., additional, Stefansson, H., additional, Walters, J., additional, Verbelen, M., additional, and Helthuis, M., additional
Published: 2015
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184. Common variant at 16p11.2 conferring risk of psychosis

Author: Steinberg, S., Jong, S. de, Mattheisen, M., Costas, J., Demontis, D., Jamain, S., Pietilainen, O.P.H., Lin, K., Papiol, S., Huttenlocher, J., Sigurdsson, E., Vassos, E., Giegling, I., Breuer, R., Fraser, G., Walker, N., Melle, I., Djurovic, S., Agartz, I., Tuulio-Henriksson, A., Suvisaari, J., Lonnqvist, J., Paunio, T., Olsen, L., Hansen, T., Ingason, A., Pirinen, M., Strengman, E., Hougaard, D.M., Orntoft, T., Didriksen, M., Hollegaard, M.V., Nordentoft, M., Abramova, L.I., Kaleda, V., Arrojo, M., Sanjuan, J., Arango, C., Etain, B., Bellivier, F., Meary, A., Schurhoff, F., Szoke, A., Ribolsi, M., Magni, V., Siracusano, A., Sperling, S., Rossner, M., Christiansen, C., Kiemeney, B., Franke, B., Berg, L.H. van den, Veldink, J., Curran, S., Bolton, P., Poot, M., Staal, W., Rehnstrom, K., Kilpinen, H., Freitag, C.M., Meyer, J., Magnusson, P., Saemundsen, E., Martsenkovsky, I., Bikshaieva, I., Martsenkovska, I., Vashchenko, O., Raleva, M., Paketchieva, K., Stefanovski, B., Durmishi, N., Milovancevic, M.P., Tosevski, D.L., Silagadze, T., Naneishvili, N., Mikeladze, N., Surguladze, S., Vincent, J.B., Farmer, A., Mitchell, P.B., Wright, A., Schofield, P.R., Fullerton, J.M., Montgomery, G.W., Martin, N.G., Rubino, I.A., Winkel, R. van, Kenis, G., Hert, M. de, Rethelyi, J.M., Bitter, I., Terenius, L., Jonsson, E.G., Bakker, S., Os, J. van, Jablensky, A., Leboyer, M., Bramon, E., et al., Steinberg, S., Jong, S. de, Mattheisen, M., Costas, J., Demontis, D., Jamain, S., Pietilainen, O.P.H., Lin, K., Papiol, S., Huttenlocher, J., Sigurdsson, E., Vassos, E., Giegling, I., Breuer, R., Fraser, G., Walker, N., Melle, I., Djurovic, S., Agartz, I., Tuulio-Henriksson, A., Suvisaari, J., Lonnqvist, J., Paunio, T., Olsen, L., Hansen, T., Ingason, A., Pirinen, M., Strengman, E., Hougaard, D.M., Orntoft, T., Didriksen, M., Hollegaard, M.V., Nordentoft, M., Abramova, L.I., Kaleda, V., Arrojo, M., Sanjuan, J., Arango, C., Etain, B., Bellivier, F., Meary, A., Schurhoff, F., Szoke, A., Ribolsi, M., Magni, V., Siracusano, A., Sperling, S., Rossner, M., Christiansen, C., Kiemeney, B., Franke, B., Berg, L.H. van den, Veldink, J., Curran, S., Bolton, P., Poot, M., Staal, W., Rehnstrom, K., Kilpinen, H., Freitag, C.M., Meyer, J., Magnusson, P., Saemundsen, E., Martsenkovsky, I., Bikshaieva, I., Martsenkovska, I., Vashchenko, O., Raleva, M., Paketchieva, K., Stefanovski, B., Durmishi, N., Milovancevic, M.P., Tosevski, D.L., Silagadze, T., Naneishvili, N., Mikeladze, N., Surguladze, S., Vincent, J.B., Farmer, A., Mitchell, P.B., Wright, A., Schofield, P.R., Fullerton, J.M., Montgomery, G.W., Martin, N.G., Rubino, I.A., Winkel, R. van, Kenis, G., Hert, M. de, Rethelyi, J.M., Bitter, I., Terenius, L., Jonsson, E.G., Bakker, S., Os, J. van, Jablensky, A., Leboyer, M., Bramon, E., and et al.
Abstract: Item does not contain fulltext, Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 x 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).
Published: 2014

185. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author: Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 135909.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

186. Biological insights from 108 schizophrenia-associated genetic loci

Author: Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, De Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, De Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, and Joa, I
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia. © 2014 Macmillan Publishers Limited. All rights reserved.
Published: 2014

187. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Author: Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
Abstract: Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014
Full Text: View/download PDF

188. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author: van den Berg, SM, de Moor, MHM, McGue, M, Pettersson, E, Terracciano, A, Verweij, KJH, Amin, Najaf, Derringer, J, Esko, T, Van Grootheest, G, Hansell, NK, Huffman, J, Konte, B, Lahti, J, Luciano, M, Matteson, LK, Viktorin, A, Wouda, J, Agrawal, A, Allik, J, Bierut, L, Broms, U, Campbell, H, Smith, GD, Eriksson, JG, Ferrucci, L, Franke, B, Fox, JP, de Geus, EJC, Giegling, I, Gow, AJ, Grucza, R, Hartmann, AM, Heath, AC, Heikkila, K, Iacono, W, Janzing, J, Jokela, M, Kiemeney, L, Lehtimaki, T, Madden, PAF, Magnusson, PKE, Northstone, K, Nutile, T, Ouwens, KG, Palotie, A, Pattie, A, Pesonen, AK, Polasek, O, Pulkkinen, L, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Seppala, I, Slutske, WS, Smyth, DC, Sorice, R, Starr, JM, Sutin, AR, Tanaka, T, Verhagen, J, Vermeulen, Shanna, Vuoksimaa, E, Widen, E, Willemsen, G, Wright, M, Zgaga, L, Rujescu, D, Metspalu, A, Wilson, JF, Ciullo, M, Hayward, C, Rudan, I, Deary, IJ, Raikkonen, K, Vasquez, AA, Costa, PT, Keltikangas-Jarvinen, L, Duijn, Cornelia, Penninx, BWJH, Krueger, RF, Evans, DM, Kaprio, J, Pedersen, NL, Martin, NG, Boomsma, DI, van den Berg, SM, de Moor, MHM, McGue, M, Pettersson, E, Terracciano, A, Verweij, KJH, Amin, Najaf, Derringer, J, Esko, T, Van Grootheest, G, Hansell, NK, Huffman, J, Konte, B, Lahti, J, Luciano, M, Matteson, LK, Viktorin, A, Wouda, J, Agrawal, A, Allik, J, Bierut, L, Broms, U, Campbell, H, Smith, GD, Eriksson, JG, Ferrucci, L, Franke, B, Fox, JP, de Geus, EJC, Giegling, I, Gow, AJ, Grucza, R, Hartmann, AM, Heath, AC, Heikkila, K, Iacono, W, Janzing, J, Jokela, M, Kiemeney, L, Lehtimaki, T, Madden, PAF, Magnusson, PKE, Northstone, K, Nutile, T, Ouwens, KG, Palotie, A, Pattie, A, Pesonen, AK, Polasek, O, Pulkkinen, L, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Seppala, I, Slutske, WS, Smyth, DC, Sorice, R, Starr, JM, Sutin, AR, Tanaka, T, Verhagen, J, Vermeulen, Shanna, Vuoksimaa, E, Widen, E, Willemsen, G, Wright, M, Zgaga, L, Rujescu, D, Metspalu, A, Wilson, JF, Ciullo, M, Hayward, C, Rudan, I, Deary, IJ, Raikkonen, K, Vasquez, AA, Costa, PT, Keltikangas-Jarvinen, L, Duijn, Cornelia, Penninx, BWJH, Krueger, RF, Evans, DM, Kaprio, J, Pedersen, NL, Martin, NG, and Boomsma, DI
Abstract: Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in > 160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

189. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis

Author: Es, M.A. van, Veldink, J.H., Saris, C.G.J., Blauw, H.M., Vught, P.W. van, Birve, A., Lemmens, R., Schelhaas, H.J., Groen, E.J., Huisman, M.H., Kooi, A.J. van der, Visser, M. de, Dahlberg, C., Estrada, K., Rivadeneira, F., Hofman, A., Zwarts, M.J., Doormaal, P.T. van, Rujescu, D., Strengman, E., Giegling, I., Muglia, P., Tomik, B., Slowik, A., Uitterlinden, A.G., Hendrich, C., Waibel, S., Meyer, T., Ludolph, A.C., Glass, J.D., Purcell, S., Cichon, S., Nothen, Markus, Wichmann, H.E., Schreiber, S., Vermeulen, S., Kiemeney, L.A.L.M., Wokke, J.H.J., Cronin, S., McLaughlin, R.L., Hardiman, O., Fumoto, K., Pasterkamp, R.J., Meininger, V., Melki, J., Leigh, P.N., Shaw, C.E., Landers, J.E., Al-Chalabi, A., Brown Jr., R.H., Robberecht, W., Andersen, P.M., Ophoff, R.A., and Berg, L.H. van den
Abstract: We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
Published: 2009

190. Disruption of the neurexin 1 gene is associated with schizophrenia

Author: Toulopoulou, T, Wiersma, D, Murray, R, Ruggeri, M, Tosato, S, Bonetto, C, Steinberg, S, Sigurdsson, E, Sigmundsson, T, Petursson, H, Gylfason, A, Olason, PI, Hardarsson, G, Jonsdottir, GA, Cahn, W, de Haan, L, Krabbendam, L, MyinGermeys, I, Werge, T, Kiemeney, LA, Franke, B, Pietiläinen, OPH, Picchioni, M, Vassos, E, Ettinger, U, Rietschel, M, Gustafsson, O, BuizerVoskamp, JE, Fossdal, R, Giegling, I, Sabatti, C, Ophoff, RA, Möller, HJ, Hartmann, AM, Hoffmann, P, Crombie, C, Rujescu, D, Veltman, J, Fraser, G, St Clair, D, Peltonen, L, Stefansson, K, Barnes, MR, Ingason, A, Stefansson, H, Nöthen, MM, Walker, N, Lonnqvist, J, Suvisaari, J, TuulioHenriksson, A, Djurovic, S, Collier, DA, Kahn, RS, Melle, I, Andreassen, OA, Hansen, T, Linszen, D, von Os, J, Bramon, E, Cichon, S, Bruggeman, R, ANS - Amsterdam Neuroscience, Adult Psychiatry, Germeys, Inez, Clinical Child and Family Studies, LEARN! - Brain, learning and development, and Faculteit Medische Wetenschappen/UMCG
Subjects: Male, Genetics and epigenetic pathways of disease [NCMLS 6], Gene Dosage, Aetiology, screening and detection [ONCOL 5], CARDIO-FACIAL SYNDROME, 0302 clinical medicine, Gene Duplication, Gene duplication, Perception and Action [DCN 1], HUMAN GENOME, Copy-number variation, European Continental Ancestry Group/genetics, Neural Cell Adhesion Molecules, POPULATION, Genetics (clinical), RISK, Genetics, 0303 health sciences, education.field_of_study, Schizophrenia/*genetics, REARRANGEMENTS, General Medicine, Exons, Nerve Tissue Proteins/*genetics, Penetrance, 3. Good health, Female, Molecular Sequence Numbers, Functional Neurogenomics [DCN 2], Adult, Psychosis, Adolescent, Cell Adhesion Molecules, Neuronal, Population, European Continental Ancestry Group, Nerve Tissue Proteins, COPY-NUMBER VARIATION, Biology, Gene dosage, Article, White People, STRUCTURAL VARIANTS, Genomic disorders and inherited multi-system disorders [IGMD 3], Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Young Adult, Translational research [ONCOL 3], mental disorders, medicine, Humans, MICRODELETION, Genetic Predisposition to Disease, Gene Silencing, education, Molecular Biology, 030304 developmental biology, Genetic association, Hereditary cancer and cancer-related syndromes [ONCOL 1], AUTISM SPECTRUM DISORDER, Calcium-Binding Proteins, Case-Control Studies, Gene Deletion, Breakpoint, ADVANCING PATERNAL AGE, medicine.disease, Schizophrenia, 030217 neurology & neurosurgery
Abstract: Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from seven European populations (Iceland, Finland, Norway, Germany, The Netherlands, Italy and UK) using microarray data. We found 66 deletions and 5 duplications in NRXN1, including a de novo deletion: 12 deletions and 2 duplications occurred in schizophrenia cases (0.47%) compared to 49 and 3 (0.15%) in controls. There was no common breakpoint and the CNVs varied from 18 to 420 kb. No CNVs were found in NRXN2 or NRXN3. We performed a Cochran-Mantel-Haenszel exact test to estimate association between all CNVs and schizophrenia (P = 0.13; OR = 1.73; 95% CI 0.81-3.50). Because the penetrance of NRXN1 CNVs may vary according to the level of functional impact on the gene, we next restricted the association analysis to CNVs that disrupt exons (0.24% of cases and 0.015% of controls). These were significantly associated with a high odds ratio (P = 0.0027; OR 8.97, 95% CI 1.8-51.9). We conclude that NRXN1 deletions affecting exons confer risk of schizophrenia. © The Author 2008. Published by Oxford University Press. All rights reserved., link_to_OA_fulltext
Published: 2009

191. A genome-wide investigation of SNPs and CNVs in schizophrenia

Author: Need, Ac, Ge, D, Weale, Me, Maia, J, Feng, S, Heinzen, El, Shianna, Kv, Yoon, W, Kasperavici, Te, D, Gennarelli, Massimo, Strittmatter, Wj, Bonvicini, C, Rossi, G, Jayathilake, K, Cola, Pa, Mcevoy, Jp, Keefe, Rs, Fisher, Em, ST JEAN PL, Giegling, I, Hartmann, Am, Möller, Hj, Ruppert, A, Fraser, G, Crombie, C, Middleton, Lt, ST CLAIR, D, Roses, Ad, Muglia, P, Francks, C, Rujescu, D, Meltzer, Hy, and Goldstein, Db
Published: 2009

192. Common variants conferring risk of schizophrenia

Author: Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Chichon, S., Rujescu, D., Werge, T., Pietilainen, O. P., Mors, O., Mortensen, P. B., Sigurdsson, E., Gustafsson, O., Nyegaard, M., Tuulio Henriksson, A., Ingason, A., Hansen, T., Suvisaari, J., Lonnqvist, J., Paunio, T., Borglum, A. D., Hartmann, A., Fink Jensen, A., Nordentoft, M., Hougaard, D., Norgaard Petersen, B., Bottcher, J., Olesen, J., Breuer, R., Moller, H. J., Giegling, I., Rasmussen, H. B., Timm, S., Mattheisen, M., Bitter, I., Rethelyi, J. M., Magnusdottir, B. B., Sigmundsson, T., Olason, P. I., Masson, G., Gulcher, J. R., Haraldsson, M., Fossdal, R., Thorgeirsson, T. E., Thorsteinsdottir, U., Ruggeri, Mirella, Tosato, Sarah, Franke, B., Strengman, E., Kiemeney, L. A., Group, Melle, I., Djurovic, S., Abramova, I., Kaleda, V., Sanjuan, J., de Frutos, R., Bramon, E., Vassos, E., Fraser, G., Ettinger, U., Picchioni, M., Walker, N., Toulopoulou, T., Need, A. C., Ge, D., Lim Yoon, J., Shianna, K. V., Freimer, N. B., Cator, R. M., Murray, R., Kong, A., Golimbet, V., Carracedo, A., Arango, C., Costas, J., Jonsson, E. G., Terenius, L., Agartz, I., Petursson, H., Nothen, M. M., Rietschel, M., Matthews, P. M., Muglia, P., Peltonen, L., St Clair, D., Goldstein, D. B., Collier, D., Genetic, Risk, Outcome in Psychosis, Kahn, R. S., Linszen, D. H., Van Os, J., Wiersma, D., Bruggeman, R., Cahn, H., de Haan, L., Krabbendam, L., Myin Germeys, I., ANS - Amsterdam Neuroscience, Adult Psychiatry, deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland., Clinical Child and Family Studies, LEARN! - Brain, learning and development, and Germeys, Inez
Subjects: Pair 6/genetics, Genetics and epigenetic pathways of disease [NCMLS 6], Genome-wide association study, Aetiology, screening and detection [ONCOL 5], 1Q21.1, Major Histocompatibility Complex/genetics, Major Histocompatibility Complex, Transcription Factor 4, 0302 clinical medicine, Chemicals And Cas Registry Numbers, Perception and Action [DCN 1], Copy-number variation, POPULATION, Genetics, Pair 18/genetics, 0303 health sciences, education.field_of_study, Genome, Human/genetics, Multidisciplinary, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Schizophrenia/*genetics/immunology, Genetic Predisposition to Disease/*genetics, 3. Good health, DNA-Binding Proteins, Neurogranin/genetics, DISEASES, Chromosomes, Human, Pair 6, Single Nucleotide/*genetics, Functional Neurogenomics [DCN 2], Zinc finger protein 804A, Human, Genetic Markers, Psychosis, Genotype, Population, Transcription Factors/genetics, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Chromosomes, Pair 11/genetics, Article, DNA-Binding Proteins/genetics, Genetic Markers/genetics, Genome-Wide Association Study, Humans, Polymorphism, Genomic disorders and inherited multi-system disorders [IGMD 3], Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Translational research [ONCOL 3], medicine, SNP, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, 030304 developmental biology, Genetic association, Hereditary cancer and cancer-related syndromes [ONCOL 1], Genome, Human, Chromosomes, Human, Pair 11, MEMORY, medicine.disease, GENE, NEUROGRANIN, DELETIONS, Schizophrenia, biology.protein, Neurogranin, Chromosomes, Human, Pair 18, MENTAL-RETARDATION, SCAN, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the ĝ€ genomic disordersĝ€™, have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition. © 2009 Macmillan Publishers Limited., link_to_OA_fulltext
Published: 2009

193. Large recurrent microdeletions associated with schizophrenia

Author: Toulopoulou, T, Franke, B, Crombie, C, Fossdal, R, Sigmundsson, T, BuizerVoskamp, JE, Hansen, T, Jakobsen, KD, Muglia, P, Francks, C, Matthews, PM, Murray, R, Ruggeri, M, Sabatti, C, Gylfason, A, Halldorsson, BV, Vassos, E, Tosato, S, Walshe, M, Freimer, NB, Gulcher, JR, Gudbjartsson, D, Thorsteinsdottir, U, Kong, A, Thorgeirsson, TE, Olesen, J, Vasilescu, C, Andreassen, OA, Melle, I, Mühleisen, TW, Wang, AG, Ullum, H, Need, AC, Sigurdsson, A, Jonasdottir, A, Djurovic, S, Ophoff, RA, Georgi, A, Rietschel, M, Werge, T, Bjornsson, A, Mattiasdottir, S, Blondal, T, Haraldsson, M, Petursson, H, MyinGermeys, I, Krabbendam, L, De Haan, L, Cahn, W, Bruggeman, R, Wiersma, D, Goldstein, DB, Nöthen, MM, Peltonen, L, Van Os, J, Linszen, DH, Kahn, RS, Stefansson, K, Magnusdottir, BB, Di Forti, M, Bramon, E, Paunio, T, TuulioHenriksson, A, Giegling, I, Möller, HJ, Suvisaari, J, Hartmann, A, Shianna, KV, Ge, D, Lonnqvist, J, Collier, DA, Walker, N, Li, T, Fraser, G, Ingason, A, Steinberg, S, Sigurdsson, E, St Clair, D, Kiemeney, LA, Stefansson, H, Rujescu, D, Cichon, S, Pietiläinen, OPH, ANS - Amsterdam Neuroscience, and Adult Psychiatry
Subjects: Schizophrenia/genetics, Genetics and epigenetic pathways of disease [NCMLS 6], Loss of Heterozygosity, Aetiology, screening and detection [ONCOL 5], Bioinformatics, China, Chromosomes, Human, Pair 1/genetics, Pair 15/genetics, Europe, Gene Dosage/genetics, Genetic Predisposition to Disease/genetics, Genome, Human/genetics, Genotype, Models, Genetic, Polymorphism, Single Nucleotide/genetics, Psychotic Disorders/genetics, Sequence Deletion/genetics, Perception and Action [DCN 1], Determinants in Health and Disease [EBP 1], Copy-number variation, Molecular diagnosis, prognosis and monitoring [UMCN 1.2], Genetics, education.field_of_study, Multidisciplinary, biology, CHRNA7, Fragile X syndrome, References (31) View In Table Layout, Schizophrenia, Functional Neurogenomics [DCN 2], Psychosis, Population, Single-nucleotide polymorphism, Article, Genomic disorders and inherited multi-system disorders [IGMD 3], Molecular epidemiology [NCEBP 1], Cognitive neurosciences [UMCN 3.2], Translational research [ONCOL 3], mental disorders, medicine, education, Hereditary cancer and cancer-related syndromes [ONCOL 1], medicine.disease, Genetic defects of metabolism [UMCN 5.1], biology.protein, Autism
Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia. ©2008 Macmillan Publishers Limited. All rights reserved., link_to_OA_fulltext
Published: 2008

194. Large recurrent microdeletions associated with schizophrenia [Letter to Nature]

Author: Stefansson, H., Rujescu, D., Cichon, S., Pietilainen, O., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., Buizer-Voskamp, J., Hansen, T., Jakobsen, K., Muglia, P., Francks, C., Matthews, P., Gylfason, A., Halldorsson, B., Gudbjartsson, D., Thorgeirsson, T., Sigurdsson, A., Jonasdottir, A., Bjornsson, A., Mattiasdottir, S., Blondal, T., Haraldsson, M., Magnusdottir, B., Giegling, I., Möller, H., Hartmann, A., Shianna, K., Ge, D., Need, A., Crombie, C., Fraser, G., Walker, N., Lonnqvist, J., Suvisaari, J., Tuulio-Henriksson, A., Paunio, T., Toulopoulou, T., Bramon, E., Forti, M., Murray, R., Ruggeri, M., Vassos, E., Tosato, S., Walshe, M., Li, T., Vasilescu, C., Muhleisen, T., Wang, A., Ullum, H., Djurovic, S., Melle, I., Olesen, J., Kiemeney, L., Franke, B., Sabatti, C., Freimer, N., Gulcher, J., Thorsteinsdottir, U., Kong, A., Andreassen, O., Ophoff, R., Georgi, A., Rietschel, M., Werge, T., Petursson, H., Goldstein, D., Nothen, M., Peltonen, L., Collier, D., St. Clair, D., and Stefansson, K.
Subjects: mental disorders
Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.
Published: 2008

195. P.5.c.005 - Patient-specific and in vitro models for the analysis of late-onset Alzheimer’s disease

Author: Ehrhardt, T., Jung, M., Hartmann, C., Giegling, I., and Rujescu, D.
Published: 2017
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196. P.1.c.017 - Modeling molecular and cellular phenotypes in schizophrenia-specific cortical neurons

Author: Jung, M., Puls, A., Schiller, J., Klemenz, A., Giegling, I., and Rujescu, D.
Published: 2017
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197. Duplications in RB1CC1 are associated with schizophrenia; identification in large European sample sets.

Author: Degenhardt, F, Degenhardt, F, Priebe, L, Meier, S, Lennertz, L, Streit, F, Witt, SH, Hofmann, A, Becker, T, Mössner, R, Maier, W, Nenadic, I, Sauer, H, Mattheisen, M, Buizer-Voskamp, J, Ophoff, RA, GROUP Consortium, Rujescu, D, Giegling, I, Ingason, A, Wagner, M, Delobel, B, Andrieux, J, Meyer-Lindenberg, A, Heinz, A, Walter, H, Moebus, S, Corvin, A, Wellcome Trust Case Control Consortium 2, International Schizophrenia Consortium, Rietschel, M, Nöthen, MM, Cichon, S, Degenhardt, F, Degenhardt, F, Priebe, L, Meier, S, Lennertz, L, Streit, F, Witt, SH, Hofmann, A, Becker, T, Mössner, R, Maier, W, Nenadic, I, Sauer, H, Mattheisen, M, Buizer-Voskamp, J, Ophoff, RA, GROUP Consortium, Rujescu, D, Giegling, I, Ingason, A, Wagner, M, Delobel, B, Andrieux, J, Meyer-Lindenberg, A, Heinz, A, Walter, H, Moebus, S, Corvin, A, Wellcome Trust Case Control Consortium 2, International Schizophrenia Consortium, Rietschel, M, Nöthen, MM, and Cichon, S
Abstract: Schizophrenia (SCZ) is a severe and debilitating neuropsychiatric disorder with an estimated heritability of ~80%. Recently, de novo mutations, identified by next-generation sequencing (NGS) technology, have been suggested to contribute to the risk of developing SCZ. Although these studies show an overall excess of de novo mutations among patients compared with controls, it is not easy to pinpoint specific genes hit by de novo mutations as actually involved in the disease process. Importantly, support for a specific gene can be provided by the identification of additional alterations in several independent patients. We took advantage of existing genome-wide single-nucleotide polymorphism data sets to screen for deletions or duplications (copy number variations, CNVs) in genes previously implicated by NGS studies. Our approach was based on the observation that CNVs constitute part of the mutational spectrum in many human disease-associated genes. In a discovery step, we investigated whether CNVs in 55 candidate genes, suggested from NGS studies, were more frequent among 1637 patients compared with 1627 controls. Duplications in RB1CC1 were overrepresented among patients. This finding was followed-up in large, independent European sample sets. In the combined analysis, totaling 8461 patients and 112 871 controls, duplications in RB1CC1 were found to be associated with SCZ (P=1.29 × 10(-5); odds ratio=8.58). Our study provides evidence for rare duplications in RB1CC1 as a risk factor for SCZ.
Published: 2013

198. The Role of the Major Histocompatibility Complex Region in Cognition and Brain Structure: A Schizophrenia GWAS Follow-Up

Author: Walters, J.T., Rujescu, D., Franke, B., Giegling, I., Arias Vasquez, A., Hargreaves, A., Russo, G., Morris, D.W., Hoogman, M., Costa, A., Moskvina, V., Fernandez, G.S.E., Gill, M., Corvin, A., O'Donovan, M.C., Donohoe, G., Owen, M.J., Walters, J.T., Rujescu, D., Franke, B., Giegling, I., Arias Vasquez, A., Hargreaves, A., Russo, G., Morris, D.W., Hoogman, M., Costa, A., Moskvina, V., Fernandez, G.S.E., Gill, M., Corvin, A., O'Donovan, M.C., Donohoe, G., and Owen, M.J.
Abstract: Item does not contain fulltext, OBJECTIVE The authors investigated the effects of recently identified genome-wide significant schizophrenia genetic risk variants on cognition and brain structure. METHOD A panel of six single-nucleotide polymorphisms (SNPs) was selected to represent genome-wide significant loci from three recent genome-wide association studies (GWAS) for schizophrenia and was tested for association with cognitive measures in 346 patients with schizophrenia and 2,342 healthy comparison subjects. Nominally significant results were evaluated for replication in an independent case-control sample. For SNPs showing evidence of association with cognition, associations with brain structural volumes were investigated in a large independent healthy comparison sample. RESULTS Five of the six SNPs showed no significant association with any cognitive measure. One marker in the major histocompatibility complex (MHC) region, rs6904071, showed independent, replicated evidence of association with delayed episodic memory and was significant when both samples were combined. In the combined sample of up to 3,100 individuals, this SNP was associated with widespread effects across cognitive domains, although these additional associations were no longer significant after adjusting for delayed episodic memory. In the large independent structural imaging sample, the same SNP was also associated with decreased hippocampal volume. CONCLUSIONS The authors identified a SNP in the MHC region that was associated with cognitive performance in patients with schizophrenia and healthy comparison subjects. This SNP, rs6904071, showed a replicated association with episodic memory and hippocampal volume. These findings implicate the MHC region in hippocampal structure and functioning, consistent with the role of MHC proteins in synaptic development and function. Follow-up of these results has the potential to provide insights into the pathophysiology of schizophrenia and cognition.
Published: 2013

199. Follow-up of schizophrenia GWAS implicates the MHC region in cognition and brain structure.

Author: Walters, J.T., Rujescu, D., Franke, B., Giegling, I., Arias Vasquez, A., Hargreaves, A., Ruso, G., Morris, D.W., Hoogman, M., Costa, A., Moskvina, V., Fernandez, G.S.E., Gill, M., Corvin, A., O'Donovan, M., Donohue, G., Owen, M., Walters, J.T., Rujescu, D., Franke, B., Giegling, I., Arias Vasquez, A., Hargreaves, A., Ruso, G., Morris, D.W., Hoogman, M., Costa, A., Moskvina, V., Fernandez, G.S.E., Gill, M., Corvin, A., O'Donovan, M., Donohue, G., and Owen, M.
Abstract: Item does not contain fulltext
Published: 2013

200. Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT)

Author: Lencz, T, primary, Knowles, E, additional, Davies, G, additional, Guha, S, additional, Liewald, D C, additional, Starr, J M, additional, Djurovic, S, additional, Melle, I, additional, Sundet, K, additional, Christoforou, A, additional, Reinvang, I, additional, Mukherjee, S, additional, DeRosse, Pamela, additional, Lundervold, A, additional, Steen, V M, additional, John, M, additional, Espeseth, T, additional, Räikkönen, K, additional, Widen, E, additional, Palotie, A, additional, Eriksson, J G, additional, Giegling, I, additional, Konte, B, additional, Ikeda, M, additional, Roussos, P, additional, Giakoumaki, S, additional, Burdick, K E, additional, Payton, A, additional, Ollier, W, additional, Horan, M, additional, Donohoe, G, additional, Morris, D, additional, Corvin, A, additional, Gill, M, additional, Pendleton, N, additional, Iwata, N, additional, Darvasi, A, additional, Bitsios, P, additional, Rujescu, D, additional, Lahti, J, additional, Hellard, S L, additional, Keller, M C, additional, Andreassen, O A, additional, Deary, I J, additional, Glahn, D C, additional, and Malhotra, A K, additional
Published: 2013
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