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1. Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.

Author: Charney, AW, Ruderfer, DM, Stahl, EA, Moran, JL, Chambert, K, Belliveau, RA, Forty, L, Gordon-Smith, K, Di Florio, A, Lee, PH, Bromet, EJ, Buckley, PF, Escamilla, MA, Fanous, AH, Fochtmann, LJ, Lehrer, DS, Malaspina, D, Marder, SR, Morley, CP, Nicolini, H, Perkins, DO, Rakofsky, JJ, Rapaport, MH, Medeiros, H, Sobell, JL, Green, EK, Backlund, L, Bergen, SE, Juréus, A, Schalling, M, Lichtenstein, P, Roussos, P, Knowles, JA, Jones, I, Jones, LA, Hultman, CM, Perlis, RH, Purcell, SM, McCarroll, SA, Pato, CN, Pato, MT, Craddock, N, Landén, M, Smoller, JW, and Sklar, P
Subjects: Chromosomes, Human, Pair 10, Humans, Aminopeptidases, Ankyrins, Calmodulin-Binding Proteins, Calcium Channels, L-Type, Cytoskeletal Proteins, Nerve Tissue Proteins, Nuclear Proteins, Case-Control Studies, Bipolar Disorder, Psychotic Disorders, Genotype, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Chromosomes, Human, Pair 10, Calcium Channels, L-Type, Polymorphism, Single Nucleotide, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
Published: 2017

2. The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression

Author: Lavebratt, C, Olsson, S, Backlund, L, Frisén, L, Sellgren, C, Priebe, L, Nikamo, P, Träskman-Bendz, L, Cichon, S, Vawter, M P, Ösby, U, Engberg, G, Landén, M, Erhardt, S, and Schalling, M
Published: 2014
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3. An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes

Author: Scott, J., Etain, B., Manchia, M., Brichant-Petitjean, C., Geoffroy, P. A., Schulze, T., Alda, M., Bellivier, F., Amare, A., Ardau, R., Backlund, L., Baune, B., Barboza, A., Benabarre, A., Chaumette, B., Chen, H., Chillotti, C., Clark, S., Colom, F., Del Zompo, M., Dalkner, N., Dantas, C., Ferentinos, P., Garnham, J., Jamain, S., Jimenez, E., Khan, J. -P., Kuo, P., Lavebratt, C., Maj, M., Millischer, V., Monteleone, P., Pisanu, C., Potash, J., Reif, A., Reininghaus, E., Schalling, M., Schofield, P., Schubert, K., Severino, G., Slaney, C., Smith, D., Squassina, A., Tondo, L., Vieta, E., and Witt, S.
Subjects: Male, psychometrics, Bipolar Disorder, Scale (ratio), Computer science, media_common.quotation_subject, Sample (statistics), Lithium, Machine learning, computer.software_genre, clinimetrics, 03 medical and health sciences, 0302 clinical medicine, Multidimensional index, Humans, genetics, Quality (business), clinical phenotypes, Biological Psychiatry, Reliability (statistics), Retrospective Studies, media_common, Interpretability, business.industry, Confounding, Reproducibility of Results, Alda scale, 030227 psychiatry, Psychiatry and Mental health, Phenotype, lithium response, Lithium Compounds, Female, Artificial intelligence, Construct (philosophy), business, computer, 030217 neurology & neurosurgery
Abstract: Objectives The Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale) is the most widely used clinical measure of lithium response phenotypes. We assess its performance against recommended psychometric and clinimetric standards. Methods We used data from the Consortium for Lithium Genetics and a French study of lithium response phenotypes (combined sample >2500) to assess reproducibility, responsiveness, validity, and interpretability of the A scale (assessing change in illness activity), the B scale, and its items (assessing confounders of response) and the previously established response categories derived from the Total Score for the Alda scale. Results The key findings are that the B scale is vulnerable to error measurement. For example, some items contribute little to overall performance of the Alda scale (eg, B2) and that the B scale does not reliably assess a single construct (uncertainty in response). Machine learning models indicate that it may be more useful to employ an algorithm for combining the ratings of individual B items in a sequence that clarifies the noise to signal ratio instead of using a composite score. Conclusions This study highlights three important topics. First, empirical approaches can help determine which aspects of the performance of any scale can be improved. Second, the B scale of the Alda is best applied as a multidimensional index (identifying several independent confounders of the assessment of response). Third, an integrated science approach to precision psychiatry is vital, otherwise phenotypic misclassifications will undermine the reliability and validity of findings from genetics and biomarker studies.
Published: 2019

4. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author: Mullins, N. Forstner, A.J. O’Connell, K.S. Coombes, B. Coleman, J.R.I. Qiao, Z. Als, T.D. Bigdeli, T.B. Børte, S. Bryois, J. Charney, A.W. Drange, O.K. Gandal, M.J. Hagenaars, S.P. Ikeda, M. Kamitaki, N. Kim, M. Krebs, K. Panagiotaropoulou, G. Schilder, B.M. Sloofman, L.G. Steinberg, S. Trubetskoy, V. Winsvold, B.S. Won, H.-H. Abramova, L. Adorjan, K. Agerbo, E. Al Eissa, M. Albani, D. Alliey-Rodriguez, N. Anjorin, A. Antilla, V. Antoniou, A. Awasthi, S. Baek, J.H. Bækvad-Hansen, M. Bass, N. Bauer, M. Beins, E.C. Bergen, S.E. Birner, A. Bøcker Pedersen, C. Bøen, E. Boks, M.P. Bosch, R. Brum, M. Brumpton, B.M. Brunkhorst-Kanaan, N. Budde, M. Bybjerg-Grauholm, J. Byerley, W. Cairns, M. Casas, M. Cervantes, P. Clarke, T.-K. Cruceanu, C. Cuellar-Barboza, A. Cunningham, J. Curtis, D. Czerski, P.M. Dale, A.M. Dalkner, N. David, F.S. Degenhardt, F. Djurovic, S. Dobbyn, A.L. Douzenis, A. Elvsåshagen, T. Escott-Price, V. Ferrier, I.N. Fiorentino, A. Foroud, T.M. Forty, L. Frank, J. Frei, O. Freimer, N.B. Frisén, L. Gade, K. Garnham, J. Gelernter, J. Giørtz Pedersen, M. Gizer, I.R. Gordon, S.D. Gordon-Smith, K. Greenwood, T.A. Grove, J. Guzman-Parra, J. Ha, K. Haraldsson, M. Hautzinger, M. Heilbronner, U. Hellgren, D. Herms, S. Hoffmann, P. Holmans, P.A. Huckins, L. Jamain, S. Johnson, J.S. Kalman, J.L. Kamatani, Y. Kennedy, J.L. Kittel-Schneider, S. Knowles, J.A. Kogevinas, M. Koromina, M. Kranz, T.M. Kranzler, H.R. Kubo, M. Kupka, R. Kushner, S.A. Lavebratt, C. Lawrence, J. Leber, M. Lee, H.-J. Lee, P.H. Levy, S.E. Lewis, C. Liao, C. Lucae, S. Lundberg, M. MacIntyre, D.J. Magnusson, S.H. Maier, W. Maihofer, A. Malaspina, D. Maratou, E. Martinsson, L. Mattheisen, M. McCarroll, S.A. McGregor, N.W. McGuffin, P. McKay, J.D. Medeiros, H. Medland, S.E. Millischer, V. Montgomery, G.W. Moran, J.L. Morris, D.W. Mühleisen, T.W. O’Brien, N. O’Donovan, C. Olde Loohuis, L.M. Oruc, L. Papiol, S. Pardiñas, A.F. Perry, A. Pfennig, A. Porichi, E. Potash, J.B. Quested, D. Raj, T. Rapaport, M.H. DePaulo, J.R. Regeer, E.J. Rice, J.P. Rivas, F. Rivera, M. Roth, J. Roussos, P. Ruderfer, D.M. Sánchez-Mora, C. Schulte, E.C. Senner, F. Sharp, S. Shilling, P.D. Sigurdsson, E. Sirignano, L. Slaney, C. Smeland, O.B. Smith, D.J. Sobell, J.L. Søholm Hansen, C. Soler Artigas, M. Spijker, A.T. Stein, D.J. Strauss, J.S. Świątkowska, B. Terao, C. Thorgeirsson, T.E. Toma, C. Tooney, P. Tsermpini, E.-E. Vawter, M.P. Vedder, H. Walters, J.T.R. Witt, S.H. Xi, S. Xu, W. Yang, J.M.K. Young, A.H. Young, H. Zandi, P.P. Zhou, H. Zillich, L. Adolfsson, R. Agartz, I. Alda, M. Alfredsson, L. Babadjanova, G. Backlund, L. Baune, B.T. Bellivier, F. Bengesser, S. Berrettini, W.H. Blackwood, D.H.R. Boehnke, M. Børglum, A.D. Breen, G. Carr, V.J. Catts, S. Corvin, A. Craddock, N. Dannlowski, U. Dikeos, D. Esko, T. Etain, B. Ferentinos, P. Frye, M. Fullerton, J.M. Gawlik, M. Gershon, E.S. Goes, F.S. Green, M.J. Grigoroiu-Serbanescu, M. Hauser, J. Henskens, F. Hillert, J. Hong, K.S. Hougaard, D.M. Hultman, C.M. Hveem, K. Iwata, N. Jablensky, A.V. Jones, I. Jones, L.A. Kahn, R.S. Kelsoe, J.R. Kirov, G. Landén, M. Leboyer, M. Lewis, C.M. Li, Q.S. Lissowska, J. Lochner, C. Loughland, C. Martin, N.G. Mathews, C.A. Mayoral, F. McElroy, S.L. McIntosh, A.M. McMahon, F.J. Melle, I. Michie, P. Milani, L. Mitchell, P.B. Morken, G. Mors, O. Mortensen, P.B. Mowry, B. Müller-Myhsok, B. Myers, R.M. Neale, B.M. Nievergelt, C.M. Nordentoft, M. Nöthen, M.M. O’Donovan, M.C. Oedegaard, K.J. Olsson, T. Owen, M.J. Paciga, S.A. Pantelis, C. Pato, C. Pato, M.T. Patrinos, G.P. Perlis, R.H. Posthuma, D. Ramos-Quiroga, J.A. Reif, A. Reininghaus, E.Z. Ribasés, M. Rietschel, M. Ripke, S. Rouleau, G.A. Saito, T. Schall, U. Schalling, M. Schofield, P.R. Schulze, T.G. Scott, L.J. Scott, R.J. Serretti, A. Shannon Weickert, C. Smoller, J.W. Stefansson, H. Stefansson, K. Stordal, E. Streit, F. Sullivan, P.F. Turecki, G. Vaaler, A.E. Vieta, E. Vincent, J.B. Waldman, I.D. Weickert, T.W. Werge, T. Wray, N.R. Zwart, J.-A. Biernacka, J.M. Nurnberger, J.I. Cichon, S. Edenberg, H.J. Stahl, E.A. McQuillin, A. Di Florio, A. Ophoff, R.A. Andreassen, O.A. HUNT All-In Psychiatry
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
Published: 2021

5. Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder

Author: Bergen, S E, O'Dushlaine, C T, Ripke, S, Lee, P H, Ruderfer, D M, Akterin, S, Moran, J L, Chambert, K D, Handsaker, R E, Backlund, L, Ösby, U, McCarroll, S, Landen, M, Scolnick, E M, Magnusson, P K E, Lichtenstein, P, Hultman, C M, Purcell, S M, Sklar, P, and Sullivan, P F
Published: 2012
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6. Clinical significance of EGFR amplification and the aberrant EGFRvIII transcript in conventionally treated astrocytic gliomas

Author: Liu, Lu, Backlund, L. Magnus, Nilsson, Bo R., Grander, Dan, Ichimura, Koichi, Goike, Helena M., and Collins, V. Peter
Subjects: Gliomas -- Chemical properties, Gliomas -- Physiological aspects, Science and technology
Published: 2005

7. Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder

Author: Bergenʼ, S E, OʼDushlaine, C T, Ripke, S, Lee, P H, Ruderfer, D M, Akterin, S, Moran, J L, Chambert, K D, Handsaker, R E, Backlund, L, sby, U O, McCarroll, S, Landen, M, Scolnick, E M, Magnusson, PKE, Lichtenstein, P, Hultman, C M, Purcell, S M, Sklar, P, and Sullivan, P F
Published: 2012
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8. Lithium treatment and cancer incidence in bipolar disorder – a large nationwide Swedish register study

Author: Martinsson, L., primary, Westman, J., additional, Hällgren, J., additional, Ösby, U., additional, and Backlund, L., additional
Published: 2019
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9. An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes.

Author: Scott, Jan, Etain, Bruno, Manchia, Mirko, Brichant‐Petitjean, Clara, Geoffroy, Pierre A., Schulze, Thomas, Alda, Martin, Bellivier, Frank, Amare, A, Ardau, R, Backlund, L, Baune, B, Barboza, A, Benabarre, A, Chaumette, B, Chen, H, Chillotti, C, Clark, S, Colom, F, and Del Zompo, M
Subjects: THERAPEUTIC use of lithium, SIGNAL-to-noise ratio, MEASUREMENT errors, PHENOTYPES
Abstract: Objectives: The Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale) is the most widely used clinical measure of lithium response phenotypes. We assess its performance against recommended psychometric and clinimetric standards. Methods: We used data from the Consortium for Lithium Genetics and a French study of lithium response phenotypes (combined sample >2500) to assess reproducibility, responsiveness, validity, and interpretability of the A scale (assessing change in illness activity), the B scale, and its items (assessing confounders of response) and the previously established response categories derived from the Total Score for the Alda scale. Results: The key findings are that the B scale is vulnerable to error measurement. For example, some items contribute little to overall performance of the Alda scale (eg, B2) and that the B scale does not reliably assess a single construct (uncertainty in response). Machine learning models indicate that it may be more useful to employ an algorithm for combining the ratings of individual B items in a sequence that clarifies the noise to signal ratio instead of using a composite score. Conclusions: This study highlights three important topics. First, empirical approaches can help determine which aspects of the performance of any scale can be improved. Second, the B scale of the Alda is best applied as a multidimensional index (identifying several independent confounders of the assessment of response). Third, an integrated science approach to precision psychiatry is vital, otherwise phenotypic misclassifications will undermine the reliability and validity of findings from genetics and biomarker studies. [ABSTRACT FROM AUTHOR]
Published: 2020
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10. Factors influencing the quality of sickness certificates in primary care in Sweden

Author: Fresk, M, primary, Backlund, L, additional, Arrelöv, B, additional, Skånér, Y, additional, Henriksson, P, additional, and Kiessling, A, additional
Published: 2017
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11. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author: O’dushlaine, C, Rossin, L, Lee, PH, Duncan, L, Parikshak, NN, Newhouse, S, Ripke, S, Neale, BM, Purcell, SM, Posthuma, D, Nurnberger, JI, Lee, SH, Faraone, SV, Perlis, RH, Mowry, BJ, Thapar, A, Goddard, ME, Witte, JS, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, OA, Anjorin, A, Anney, R, Anttila, V, Arking, DE, Asherson, P, Azevedo, MH, Backlund, L, Badner, JA, Bailey, AJ, Banaschewski, T, Barchas, JD, Barnes, MR, Barrett, TB, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, SE, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, EB, Black, DW, Blackwood, DHR, Bloss, CS, Boehnke, M, Boomsma, DI, Breuer, R, Bruggeman, R, Cormican, P, Buccola, NG, Buitelaar, JK, Bunney, WE, Buxbaum, JD, Byerley, WF, Byrne, EM, Caesar, S, Cahn, W, Cantor, RM, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, and Cichon, S
Abstract: © 2015 Nature America, Inc. All rights reserved. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
Published: 2015

12. Detection Rate and Lead Times for Diagnosis of Cutaneous Malignant Melanoma - a Cross-Sectional Study at Two Dermatology Clinics in Sweden

Author: Backlund, L Magnus, primary
Published: 2016
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13. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder

Author: Sellgren, C M, primary, Kegel, M E, additional, Bergen, S E, additional, Ekman, C J, additional, Olsson, S, additional, Larsson, M, additional, Vawter, M P, additional, Backlund, L, additional, Sullivan, P F, additional, Sklar, P, additional, Smoller, J W, additional, Magnusson, P K E, additional, Hultman, C M, additional, Walther-Jallow, L, additional, Svensson, C I, additional, Lichtenstein, P, additional, Schalling, M, additional, Engberg, G, additional, Erhardt, S, additional, and Landén, M, additional
Published: 2015
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14. 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

15. 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

16. Telomerase Dysregulation in the Hippocampus of a Rat Model of Depression: Normalization by Lithium

Author: Wei, Y. B., primary, Backlund, L., additional, Wegener, G., additional, Mathe, A. A., additional, and Lavebratt, C., additional
Published: 2015
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17. Airborne Oil Spill Surveillance Systems in Sweden

Author: Backlund, L., primary
Published: 1984
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18. Randomized controlled trial of transdiagnostic group treatments for primary care patients with common mental disorders

Author: Ejeby, K., primary, Savitskij, R., additional, Ost, L.-G., additional, Ekbom, A., additional, Brandt, L., additional, Ramnero, J., additional, Asberg, M., additional, and Backlund, L. G., additional
Published: 2014
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19. Mortality in depressed and non-depressed primary care Swedish patients: a 12-year follow-up cohort study

Author: Stromberg, R., primary, Backlund, L. G., additional, Johansson, S.-E., additional, and Lofvander, M., additional
Published: 2013
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20. Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres

Author: Martinsson, L, primary, Wei, Y, additional, Xu, D, additional, Melas, P A, additional, Mathé, A A, additional, Schalling, M, additional, Lavebratt, C, additional, and Backlund, L, additional
Published: 2013
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21. The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression

Author: Lavebratt, C, primary, Olsson, S, additional, Backlund, L, additional, Frisén, L, additional, Sellgren, C, additional, Priebe, L, additional, Nikamo, P, additional, Träskman-Bendz, L, additional, Cichon, S, additional, Vawter, M P, additional, Ösby, U, additional, Engberg, G, additional, Landén, M, additional, Erhardt, S, additional, and Schalling, M, additional
Published: 2013
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22. P-163 - P2RX7: Expression responds to sleep deprivation and associates with rapid cycling in bipolar disorder type 1

Author: Backlund, L., primary, Lavebratt, C., additional, Frisen, L., additional, Nikamo, P., additional, Vawter, M.P., additional, Hukic Sudic, D., additional, Träskman-Bendz, L., additional, Landén, M., additional, Edman, G., additional, and Schalling, M., additional
Published: 2012
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23. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder

Author: Sellgren, C M, Kegel, M E, Bergen, S E, Ekman, C J, Olsson, S, Larsson, M, Vawter, M P, Backlund, L, Sullivan, P F, Sklar, P, Smoller, J W, Magnusson, P K E, Hultman, C M, Walther-Jallow, L, Svensson, C I, Lichtenstein, P, Schalling, M, Engberg, G, Erhardt, S, and Landén, M
Abstract: Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant—associated with reduced SNX7 expression—to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1β and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder.
Published: 2016
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24. Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma

Author: McCabe, M. G., primary, Backlund, L. M., additional, Leong, H. S., additional, Ichimura, K., additional, and Collins, V. P., additional
Published: 2011
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25. Psychiatric admissions and hospitalization costs in bipolar disorder in Sweden

Author: Ösby, U., primary, Tiainen, A., additional, Backlund, L., additional, Edman, G., additional, Adler, M., additional, Hällgren, J., additional, Sennfält, K., additional, van Baardewijk, M., additional, and Sparen, P., additional
Published: 2009
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26. Psychiatric Hospitalization in bipolar disorder in Sweden

Author: Edman, G., primary, Backlund, L., additional, Adler, M., additional, Hallgren, J., additional, Sparen, P., additional, and Osby, U., additional
Published: 2008
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27. Association between G72/30 haplotypes and bipolar disorder in a Swedish sample

Author: Backlund, L., primary, Nikamo, P., additional, Rosvall, L., additional, Frisen, L., additional, Landen, M., additional, Ladanayi, J., additional, Träskman-Bendz, L., additional, Ågren, H., additional, Schalling, M., additional, and Ösby, U., additional
Published: 2008
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28. The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression.

Author: Lavebratt, C, Olsson, S, Backlund, L, Frisén, L, Sellgren, C, Priebe, L, Nikamo, P, Träskman-Bendz, L, Cichon, S, Vawter, M P, Ösby, U, Engberg, G, Landén, M, Erhardt, S, and Schalling, M
Subjects: KYNURENINE, NEURAL transmission, CEREBROSPINAL fluid, PEOPLE with schizophrenia, HUMAN genetic variation, GENE expression, LYMPHOBLASTOID cell lines
Abstract: The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P=0.005, n=19) or schizophrenia (P=0.02, n=36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg452 allele was associated with psychotic features during manic episodes (P=0.003). KMO Arg452 was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg452 associated with increased levels of CSF KYNA (P=0.03) and reduced lymphoblastoid and hippocampal KMO expression (P0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes. [ABSTRACT FROM AUTHOR]
Published: 2014
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29. Comparative Measurements Of The Mucosal Blood Flow In The Human Maxillary Sinus By Plethysmography And By Xenon.

Author: Aust, R., Backlund, L., Drettner, B., Falck, B., and Jung, B.
Published: 1978
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30. Follow-up of plasma semicarbazide-sensitive amine oxidase activity and retinopathy in Type 2 diabetes mellitus

Author: Gronvall-Nordquist, L., J., Backlund, L. B., Garpenstrand, H., Ekblom, J., Landin, B., Yu, P. H., Oreland, L., and Rosenqvist, U.
Published: 2001
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31. Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases

Author: Bromet, E.J., Jur��us, A., Malaspina, D., Knowles, J.A., Belliveau, R.A., Jr., Morley, C.P., Perlis, R., Green, E.K., Medeiros, H., Fochtmann, L.J., Backlund, L., Chambert, K., Craddock, N., Lee, P.H., Forty, L., Pato, C.N., Sobell, J.L., Jones, I., Stahl, E.A., McCarroll, S.A., Perkins, D.O., Lehrer, D.S., Charney, A.W., Gordon-Smith, K., Lichtenstein, P., Schalling, M., Chen, C.-Y., Hultman, C.M., Smoller, J.W., Di Florio, A., Land��n, M., Fanous, A.H., Marder, S.R., Sklar, P., Purcell, S.M., Pato, M.T., Rakofsky, J.J., Nicolini, H., Burdick, K.E., Jones, L.A., Moran, J.L., Buckley, P.F., Ruderfer, D.M., Rapaport, M.H., Escamilla, M.A., and Bergen, S.E.
Subjects: mental disorders, 3. Good health
Abstract: Background: Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood. Methods: Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis. Results: CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 �� 10��5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden. Conclusions: CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.

32. [ICF is a good tool to describe activity limitations in sick leave. General practitioners and the Swedish Social Insurance Agency are positive, as shown by qualitative study]

Author: Fresk M, Britt Arrelöv, Skånér Y, Backlund L, and Nilsson G

33. Association between G72 haplotypes and bipolar disorder in a Nordic sample

Author: Osby, U., Schalling, M., Agren, H., Isacsson, G., Preben Bo Mortensen, Borglum, A., Frisen, L., Traskman-Bendz, L., Kockum, I., Mors, O., Rosvall, L., and Backlund, L.

34. Nordsat - A DBS system for the Nordic countries

Author: ANDERSON, L., primary, GRAHN, S., additional, and BACKLUND, L., additional
Published: 1978
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35. Tele-X - The first step in a satellite communications system for theNordic countries

Author: BACKLUND, L., primary, ANDERSON, L., additional, EKMAN, A., additional, GRAHN, S., additional, JALMARSSON, L., additional, and LUNDSTROM, L.-I., additional
Published: 1984
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36. Functional Stenosis as a Cause of Pelvi-Ureteric Obstruction and Hydronephrosis

Author: Backlund, L., primary, Grotte, G., additional, and Reuterskiold, A., additional
Published: 1965
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37. Health problems and disability in long-term sickness absence: ICF coding of medical certificates

Author: Morgell Roland, Backlund Lars G, Arrelöv Britt, Strender Lars-Erik, and Nilsson Gunnar H
Subjects: Public aspects of medicine, RA1-1270
Abstract: Abstract Background The purpose of this study was to test the feasibility of International Classification of Functioning, Disability and Health (ICF) and to explore the distribution, including gender differences, of health problems and disabilities as reflected in long-term sickness absence certificates. Methods A total of 433 patients with long sick-listing periods, 267 women and 166 men, were included in the study. All certificates exceeding 28 days of sick-listing sent to the local office of the Swedish Social Insurance Administration of a municipality in the Stockholm area were collected during four weeks in 2004-2005. ICD-10 medical diagnosis codes in the certificates were retrieved and free text information on disabilities in body function, body structure or activity and participation were coded according to ICF short version. Results In 89.8% of the certificates there were descriptions of disabilities that readily could be classified according to ICF. In a reliability test 123/131 (94%) items of randomly chosen free text information were identically classified by two of the authors. On average 2.4 disability categories (range 0-9) were found per patient; the most frequent were 'Sensation of pain' (35.1% of the patients), 'Emotional functions' (34.1%), 'Energy and drive functions' (22.4%), and 'Sleep functions' (16.9%). The dominating ICD-10 diagnostic groups were 'Mental and behavioural disorders' (34.4%) and 'Diseases of the musculoskeletal system and connective tissue' (32.8%). 'Reaction to severe stress and adjustment disorders' (14.7%), and 'Depressive episode' (11.5%) were the most frequent diagnostic codes. Disabilities in mental functions and activity/participation were more commonly described among women, while disabilities related to the musculoskeletal system were more frequent among men. Conclusions Both ICD-10 diagnoses and ICF categories were dominated by mental and musculoskeletal health problems, but there seems to be gender differences, and ICF classification as a complement to ICD-10 could provide a better understanding of the consequences of diseases and how individual patients can cope with their health problems. ICF is feasible for secondary classifying of free text descriptions of disabilities stated in sick-leave certificates and seems to be useful as a complement to ICD-10 for sick-listing management and research.
Published: 2011
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38. Psychosocial stressors and depression at a Swedish primary health care centre. A gender perspective study

Author: Strömberg Ranja, Backlund Lars G, and Löfvander Monica
Subjects: Medicine (General), R5-920
Abstract: Abstract Background Psychosocial stress may account for the higher prevalence of depression in women and in individuals with a low educational background. The aim of this study was to analyse the association between depression and socio-demographic data, psychosocial stressors and lifestyle circumstances from a gender perspective in a relatively affluent primary care setting. Methods Patients, aged 18- 75 years, visiting a drop-in clinic at a primary care health centre were screened with Beck's Depression Inventory (BDI). The physicians used also targeted screening with BDI. A questionnaire on socio-demographic data, psychosocial stressors and use of alcohol and tobacco was distributed. Among patients, who scored BDI ≥10, DSM-IV-criteria were used to diagnose depression. Of the 404 participants, 48 men and 76 women were diagnosed with depression. The reference group consisted of patients with BDI score Results The same three psychosocial stressors: feeling very stressed, perceived poor physical health and being dissatisfied with one's family situation were associated with depression equally in men and women. The negative predictive values of the main effect models in men and women were 90.7% and 76.5%, respectively. Being dissatisfied with one's work situation had high ORs in both men and women. Unemployment and smoking were associated with depression in men only. Conclusions Three questions, frequently asked by physicians, which involve patient's family and working situation as well as perceived stress and physical health, could be used as depression indicators in early detection of depression in men and women in primary health care.
Published: 2011
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39. Knowledge of stroke risk factors among primary care patients with previous stroke or TIA: a questionnaire study

Author: Strender Lars-Erik, Backlund Lars G, Sloma Andrzej, and Skånér Ylva
Subjects: Medicine (General), R5-920
Abstract: Abstract Background Survivers of stroke or transient ischaemic attacks (TIA) are at risk of new vascular events. Our objective was to study primary health care patients with stroke/TIA regarding their knowledge about risk factors for having a new event of stroke/TIA, possible associations between patient characteristics and patients' knowledge about risk factors, and patients' knowledge about their preventive treatment for stroke/TIA. Methods A questionnaire was distributed to 240 patients with stroke/TIA diagnoses, and 182 patients (76%) responded. We asked 13 questions about diseases/conditions and lifestyle factors known to be risk factors and four questions regarding other diseases/conditions ("distractors"). The patients were also asked whether they considered each disease/condition to be one of their own. Additional questions concerned the patients' social and functional status and their drug use. The t-test was used for continuous variables, chi-square test for categorical variables, and a regression model with variables influencing patient knowledge was created. Results Hypertension, hyperlipidemia and smoking were identified as risk factors by nearly 90% of patients, and atrial fibrillation and diabetes by less than 50%. Few patients considered the distractors as stroke/TIA risk factors (3-6%). Patients with a family history of cardiovascular disease, and patients diagnosed with carotid stenosis, atrial fibrillation or diabetes, knew these were stroke/TIA risk factors to a greater extent than patients without these conditions. Atrial fibrillation or a family history of cardiovascular disease was associated with better knowledge about risk factors, and higher age, cerebral haemorrhage and living alone with poorer knowledge. Only 56% of those taking anticoagulant drugs considered this as intended for prevention, while 48% of those taking platelet aggregation inhibitors thought this was for prevention. Conclusions Knowledge about hypertension, hyperlipidemia and smoking as risk factors was good, and patients who suffered from atrial fibrillation or carotid stenosis seemed to be well informed about these conditions as risk factors. However, the knowledge level was low regarding diabetes as a risk factor and regarding the use of anticoagulants and platelet aggregation inhibitors for stroke/TIA prevention. Better teaching strategies for stroke/TIA patients should be developed, with special attention focused on diabetic patients.
Published: 2010
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40. Screening and diagnosing depression in women visiting GPs' drop in clinic in Primary Health Care

Author: Johansson Sven-Erik, Aberg-Wistedt Anna, Furhoff Anna-Karin, Wernering Estera, Stromberg Ranja, and Backlund Lars G
Subjects: Medicine (General), R5-920
Abstract: Abstract Background Only half of all depressions are diagnosed in Primary Health Care (PHC). Depression can remain undetected for a long time and entail high costs for care and low quality of life for the individuals. Drop in clinic is a common form of organizing health care; however the visits are short and focus on solving the most urgent problems. The aim of this study was to investigate the prevalence and severity of depression among women visiting the GPs' drop in clinic and to identify possible clues for depression among women. Methods The two-stage screening method with "high risk feedback" was used. Beck's Depression Inventory (BDI) was used to screen 155 women visiting two GPs' drop in clinic. Women who screened positive (BDI score ≥10) were invited by the GP to a repeat visit. Major depression (MDD) was diagnosed according to DSM-IV criteria and the severity was assessed with Montgomery-Asberg Depression Rating Scale (MADRS). Women with BDI score Results The two-stage method worked well with a low rate of withdrawals in the second step, when the GP invited the women to a repeat visit. The prevalence of depression was 22.4% (95% CI 15.6–29.2). The severity was mild in 43%, moderate in 53% and severe in 3%. The depressed women mentioned mental symptoms significantly more often (69%) than the controls (15%) and were to a higher extent sick-listed for a longer period than 14 days. Nearly one third of the depressed women did not mention mental symptoms. The majority of the women who screened as false positive for depression had crisis reactions and needed further care from health professionals in PHC. Referrals to a psychiatrist were few and revealed often psychiatric co-morbidity. Conclusion The prevalence of previously undiagnosed depression among women visiting GPs' drop in clinic was high. Clues for depression were identified in the depressed women's symptom presentation; they often mention mental symptoms when they visit the GP for somatic reasons e.g. respiratory infections. We suggest that GPs do selective screening for depression when women mention mental symptoms and offer to schedule a repeat visit for follow-up rather than just recommending that the patient return if the mental symptoms do not disappear.
Published: 2008
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41. General practitioners' reasoning when considering the diagnosis heart failure: a think-aloud study

Author: Bring Johan, Montgomery Henry, Backlund Lars, Skånér Ylva, and Strender Lars-Erik
Subjects: Medicine (General), R5-920
Abstract: Abstract Background Diagnosing chronic heart failure is difficult, especially in mild cases or early in the course of the disease, and guidelines are not easily implemented in everyday practice. The aim of this study was to investigate general practitioners' diagnostic reasoning about patients with suspected chronic heart failure in comparison with recommendations in European guidelines. Methods Think-aloud technique was used. Fifteen general practitioners reasoned about six case vignettes, representing authentic patients with suspected chronic heart failure. Information about each case was added successively in five steps. The general practitioners said their thoughts aloud while reasoning about the probability of the patient having chronic heart failure, and tried to decide about the diagnosis. Arguments for and against chronic heart failure were analysed and compared to recommendations in guidelines. Results Information about ejection fraction was the most frequent diagnostic argument, followed by information about cardiac enlargement or pulmonary congestion on chest X-ray. However, in a third of the judgement situations, no information about echocardiography was utilized in the general practitioners' diagnostic reasoning. Only three of the 15 doctors used information about a normal electrocardiography as an argument against chronic heart failure. Information about other cardio-vascular diseases was frequently used as a diagnostic argument. Conclusions The clinical information was not utilized to the extent recommended in guidelines. Some implications of our study are that 1) general practitioners need more information about how to utilize echocardiography when diagnosing chronic heart failure, 2) guidelines ought to give more importance to information about other cardio-vascular diseases in the diagnostic reasoning, and 3) guidelines ought to treat the topic of diastolic heart failure in a clearer way.
Published: 2005
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42. GPs' decisions on drug treatment for patients with high cholesterol values: A think-aloud study

Author: Bring Johan, Montgomery Henry, Skånér Ylva, Backlund Lars, and Strender Lars-Erik
Subjects: Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Abstract Background The purpose was to examine how General Practitioners (GPs) use clinical information and rules from guidelines in their decisions on drug treatment for high cholesterol values. Methods Twenty GPs were presented with six case vignettes and were instructed to think aloud while successively more information about a case was presented, and finally to decide if a drug should be prescribed or not. The statements were coded for the clinical information to which they referred and for favouring or not favouring prescription. Results The evaluation of clinical information was compatible with decision-making as a search for reasons or arguments. Lifestyle-related information like smoking and overweight seemed to be evaluated from different perspectives. A patient's smoking favoured treatment for some GPs and disfavoured treatment for others. Conclusions The method promised to be useful for understanding why doctors differ in their decisions on the same patient descriptions and why rules from the guidelines are not followed strictly.
Published: 2004
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43. The role of guidelines and the patient's life-style in GPs' management of hypercholesterolaemia

Author: Bring Johan, Montgomery Henry, Skånér Ylva, Backlund Lars, and Strender Lars-Erik
Subjects: Medicine (General), R5-920
Abstract: Abstract Background Recent Swedish and joint European guidelines on hyperlipidaemia stress the high coronary risk for patients with already established arterio-sclerotic disease (secondary prevention) or diabetes. For the remaining group, calculation of the ten-year risk for coronary events using the Framingham equation is suggested. There is evidence that use of and adherence to guidelines is incomplete and that tools for risk estimations are seldom used. Intuitive risk estimates are difficult and systematically biased. The purpose of the study was to examine how GPs use knowledge of guidelines in their decisions to recommend or not recommend a cholesterol-lowering drug and the reasons for their decisions. Methods Twenty GPs were exposed to six case vignettes presented on a computer. In the course of six screens, successively more information was added to the case. The doctors were instructed to think aloud while processing the cases (Think-Aloud Protocols) and finally to decide for or against drug treatment. After the six cases they were asked to describe how they usually reason when they meet patients with high cholesterol values (Free-Report Protocols). The two sets of protocols were coded for cause-effect relations that were supposed to reflect the doctors' knowledge of guidelines. The Think-Aloud Protocols were also searched for reasons for the decisions to prescribe or not to prescribe. Results According to the protocols, the GPs were well aware of the importance of previous coronary heart disease and diabetes in their decisions. On the other hand, only a few doctors mentioned other arterio-sclerotic diseases like stroke and peripheral artery disease as variables affecting their decisions. There were several instances when the doctors' decisions apparently deviated from their knowledge of the guidelines. The arguments for the decisions in these cases often concerned aspects of the patient's life-style like smoking or overweight- either as risk-increasing factors or as alternative strategies for intervention. Conclusions Coding verbal protocols for knowledge and for decision arguments seems to be a valuable tool for increasing our understanding of how guidelines are used in the on treatment of hypercholesterolaemia. By analysing arguments for treatment decisions it was often possible to understand why departures from the guidelines were made. While the need for decision support is obvious, the current guidelines may be too simple in some respects.
Published: 2004
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44. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., O'Connell, Kevin S., Coombes, Brandon, Qiao, Zhen, Als, Thomas D., Børte, Sigrid, Charney, Alexander W., Drange, Ole Kristian, Gandal, Michael J., Hagenaars, Saskia P., Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M., Sloofman, Laura G., Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Gizer, Ian R., Gordon-Smith, Katherine, Greenwood, Tiffany A., Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Kogevinas, Manolis, Koromina, Maria, Kranz, Thorsten M., Kranzler, Henry R., Kubo, Michiaki, Kupka, Ralph, Kushner, Steven A., Lavebratt, Catharina, Lawrence, Jacob, Leber, Markus, Lee, Heon-Jeong, Lee, Phil H., Levy, Shawn E., Lewis, Catrin, Liao, Calwing, Lundberg, Martin, Magnusson, Sigurdur H., Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, McGregor, Nathaniel W., McKay, James D., Medeiros, Helena, Millischer, Vincent, Moran, Jennifer L., Morris, Derek W., Mühleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Olde Loohuis, Loes M., Oruc, Lilijana, Papiol, Sergi, Pardiñas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Quested, Digby, Raj, Towfique, Rapaport, Mark H., Regeer, Eline J., Rivas, Fabio, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Xi, Simon, Xu, Wei, Kay Yang, Jessica Mei, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dikeos, Dimitris, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Mitchell, Philip B., Morken, Gunnar, Mowry, Bryan, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Oedegaard, Ketil J., Olsson, Tomas, Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Stordal, Eystein, Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Adan, Roger A. H., Ando, Tetsuya, Aschauer, Harald, Baker, Jessica H., Bencko, Vladimir, Bergen, Andrew W., Birgegård, Andreas, Boden, Joseph M., Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Buehren, Katharina, Bulik, Cynthia M., Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S. P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dina, Christian, Dmitrzak-Weglarz, Monika, Martinez, Elisa Docampo, Duncan, Laramie E., Egberts, Karin, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Munn-Chernoff, Melissa A., Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, Olsen, Catherine M., O'Toole, Julie K., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John F., Ehrlich, Stefan, Escaramís, Geòrgia, Espeseth, Thomas, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Floyd, James A. B., Föcker, Manuel, Foretova, Lenka, Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A., Hanscombe, Ken B., Hatzikotoulas, Konstantinos, Hebebrand, Johannes, Helder, Sietske G., Henders, Anjali K., Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Petersen, Liselotte V., Pinto, Dalila, Purves, Kirstin L., Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op 't Landt, Margarita C. T., Slopien, Agnieszka, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar W., Strober, Michael, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan S., Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J. H., Kaye, Walter H., Kennedy, Martin A., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Kirk, Katherine M., Klareskog, Lars, Klump, Kelly L., Knudsen, Gun Peggy S., Larsen, Janne T., Le Hellard, Stephanie, Leppä, Virpi M., Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lundervold, Astri, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Stuber, Garret D., Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura M., Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wade, Tracey D., Wagner, Gudrun, Walton, Esther, Watson, Hunna J., Whiteman, David C., Wichmann, H. Erich, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Jungkunz, Martin, Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M. -H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., Otsuka, I., Ripke, S., Ware, E. B., Bergen, A. W., Berrettini, W. H., Bohus, M., Brandt, H., Chang, X., Chen, W. J., Chen, H. -C., Crawford, S., Crow, S., Diblasi, E., Duriez, P., Fernandez-Aranda, F., Fichter, M. M., Gallinger, S., Glatt, S. J., Gorwood, P., Guo, Y., Hakonarson, H., Halmi, K. A., Hwu, H. -G., Jain, S., Jamain, S., Jimenez-Murcia, S., Johnson, C., Kaplan, A. S., Kaye, W. H., Keel, P. K., Kennedy, J. L., Klump, K. L., Li, D., Liao, S. -C., Lieb, K., Lilenfeld, L., Liu, C. -M., Magistretti, P. J., Marshall, C. R., Mitchell, J. E., Monson, E. T., Myers, R. M., Pinto, D., Powers, A., Ramoz, N., Roepke, S., Rozanov, V., Scherer, S. W., Schmahl, C., Sokolowski, M., Strober, M., Thornton, L. M., Treasure, J., Tsuang, M. T., Witt, S. H., Woodside, D. B., Yilmaz, Z., Zillich, L., Adolfsson, R., Agartz, I., Air, T. M., Alda, M., Alfredsson, L., Andreassen, O. A., Anjorin, A., Appadurai, V., Soler Artigas, M., Van der Auwera, S., Azevedo, M. H., Bass, N., Bau, C. H. D., Baune, B. T., Bellivier, F., Berger, K., Biernacka, J. M., Bigdeli, T. B., Binder, E. B., Boehnke, M., Boks, M. P., Bosch, R., Braff, D. L., Bryant, R., Budde, M., Byrne, E. M., Cahn, W., Casas, M., Castelao, E., Cervilla, J. A., Chaumette, B., Cichon, S., Corvin, A., Craddock, N., Craig, D., Degenhardt, F., Djurovic, S., Edenberg, H. J., Fanous, A. H., Foo, J. C., Forstner, A. J., Frye, M., Fullerton, J. M., Gatt, J. M., Gejman, P. V., Giegling, I., Grabe, H. J., Green, M. J., Grevet, E. H., Grigoroiu-Serbanescu, M., Gutierrez, B., Guzman-Parra, J., Hamilton, S. P., Hamshere, M. L., Hartmann, A., Hauser, J., Heilmann-Heimbach, S., Hoffmann, P., Ising, M., Jones, I., Jones, L. A., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kendler, K. S., Kloiber, S., Koenen, K. C., Kogevinas, M., Konte, B., Krebs, M. -O., Landen, M., Lawrence, J., Leboyer, M., Lee, P. H., Levinson, D. F., Liao, C., Lissowska, J., Lucae, S., Mayoral, F., Mcelroy, S. L., Mcgrath, P., Mcguffin, P., Mcquillin, A., Medland, S. E., Mehta, D., Melle, I., Milaneschi, Y., Mitchell, P. B., Molina, E., Morken, G., Mortensen, P. B., Muller-Myhsok, B., Nievergelt, C., Nimgaonkar, V., Nothen, M. M., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pato, C., Pato, M. T., Penninx, B. W. J. H., Pimm, J., Pistis, G., Potash, J. B., Power, R. A., Preisig, M., Quested, D., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Richarte, V., Rietschel, M., Rivera, M., Roberts, A., Roberts, G., Rouleau, G. A., Rovaris, D. L., Rujescu, D., Sanchez-Mora, C., Sanders, A. R., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Shi, J., Shyn, S. I., Sirignano, L., Sklar, P., Smeland, O. B., Smoller, J. W., Sonuga-Barke, E. J. S., Spalletta, G., Strauss, J. S., Swiatkowska, B., Trzaskowski, M., Turecki, G., Vilar-Ribo, L., Vincent, J. B., Volzke, H., Walters, J. T. R., Shannon Weickert, C., Weickert, T. W., Weissman, M. M., Williams, L. M., Wray, N. R., Zai, C. C., Ashley-Koch, A. E., Beckham, J. C., Hauser, E. R., Hauser, M. A., Kimbrel, N. A., Lindquist, J. H., Mcmahon, B., Oslin, D. W., Qin, X., Mattheisen, M., Abdellaoui, A., Adams, M. J., Agerbo, E., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Christensen, J. H., Clarke, T. -K., Colodro-Conde, L., Couvy-Duchesne, B., Crawford, G. E., Davies, G., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Hassan Kiadeh, F. F., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Goes, F. S., Gordon, S. D., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Boomsma, D. I., Dannlowski, U., Depaulo, J. R., Domenici, E., Domschke, K., Esko, T., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Herms, S., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Howard, D. M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Middeldorp, C. M., Mihailov, E., Milani, L., Mondimore, F. M., Montgomery, G. W., Mostafavi, S., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Hayward, C., Heath, A. C., Lewis, G., Li, Q. S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Nordentoft, M., Paciga, S. A., Pedersen, N. L., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Peyrot, W. J., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Mirza, S. S., Schoevers, R., Schulte, E. 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P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards 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E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.
Subjects: LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract: Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
Published: 2022

45. General practitioners' reasoning when considering the diagnosis heart failure: a think-aloud study.

Author: Skånér Y, Backlund L, Montgomery H, Bring J, and Strender LE
Abstract: BACKGROUND: Diagnosing chronic heart failure is difficult, especially in mild cases or early in the course of the disease, and guidelines are not easily implemented in everyday practice. The aim of this study was to investigate general practitioners' diagnostic reasoning about patients with suspected chronic heart failure in comparison with recommendations in European guidelines. METHODS: Think-aloud technique was used. Fifteen general practitioners reasoned about six case vignettes, representing authentic patients with suspected chronic heart failure. Information about each case was added successively in five steps. The general practitioners said their thoughts aloud while reasoning about the probability of the patient having chronic heart failure, and tried to decide about the diagnosis. Arguments for and against chronic heart failure were analysed and compared to recommendations in guidelines. RESULTS: Information about ejection fraction was the most frequent diagnostic argument, followed by information about cardiac enlargement or pulmonary congestion on chest X-ray. However, in a third of the judgement situations, no information about echocardiography was utilized in the general practitioners' diagnostic reasoning. Only three of the 15 doctors used information about a normal electrocardiography as an argument against chronic heart failure. Information about other cardio-vascular diseases was frequently used as a diagnostic argument. CONCLUSIONS: The clinical information was not utilized to the extent recommended in guidelines. Some implications of our study are that 1) general practitioners need more information about how to utilize echocardiography when diagnosing chronic heart failure, 2) guidelines ought to give more importance to information about other cardio-vascular diseases in the diagnostic reasoning, and 3) guidelines ought to treat the topic of diastolic heart failure in a clearer way. [ABSTRACT FROM AUTHOR]
Published: 2005

46. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author: Laura M. Thornton, Paul Lichtenstein, Verneri Anttila, Diego Albani, Josep Antoni Ramos-Quiroga, Roger A.H. Adan, Monika Schlögelhofer, Stephen Sanders, Enrique Castelao, Klaus Berger, Nina Dalkner, Urs Heilbronner, Engilbert Sigurdsson, Pablo Mir, Fuquan Zhang, James T.R. Walters, Patrick F. Sullivan, Fragiskos Gonidakis, F. Kyle Satterstrom, Sara Marsal, Per Hoffmann, Amy Perry, Valentina Ciullo, Beate Herpertz-Dahlmann, Catharina Lavebratt, Kieran C. Murphy, Tammy Hedderly, Hyun Ju Hong, Evald Saemundsen, Sascha B. Fischer, Hailiang Huang, Andrew D. Grotzinger, Nienke Vulink, Murray B. Stein, Mark A. Frye, Laura J. Scott, David Curtis, Todd Lencz, Janiece E. DeSocio, Richard A. Belliveau, Eduard Vieta, Andrea Dietrich, Wade H. Berrettini, Kenneth S. Kendler, Marquis P. Vawter, Paul S. Nestadt, Michael E. Talkowski, Manuel Mattheisen, Ingrid Agartz, Elisa Docampo, Bernhard T. Baune, Stefan Ehrlich, Jolanta Lissowska, Felecia Cerrato, Terje Nærland, Robin M. Murray, Jennifer Reichert, Annette M. Hartmann, Hannelore Ehrenreich, Howard J. Edenberg, Katherine A. Halmi, Qingqin S. Li, Peristera Paschou, Marie Bækvad-Hansen, Esther Walton, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Frank Bellivier, Jungeun Song, D. Blake Woodside, Young Shin Kim, Jochen Seitz, Jacques Pantel, Palmiero Monteleone, Erika L. Nurmi, Rodney J. Scott, Kang Sim, Ekaterina A. Khramtsova, Udo Dannlowski, Rolf Adolfsson, Danielle Posthuma, Melissa J. Green, Laura Ibanez-Gomez, Jakob Grove, Elvira Bramon, Gregory L. Hanna, Cynthia M. Bulik, Yiran Guo, Stephan Ripke, Mary M. Robertson, Harald N. Aschauer, Adebayo Anjorin, Joanna Martin, Bertram Müller-Myhsok, Deborah Kaminská, Jose Guzman-Parra, Benedetta Nacmias, Erik G. Jönsson, Jonathan R. I. Coleman, Douglas F. Levinson, Hamdi Mbarek, Gun Peggy Knudsen, Karin Egberts, Mette Nyegaard, Patrik K. E. Magnusson, Mark Adams, Douglas Blackwood, Elisabeth B. Binder, Marcus Ising, Anna R. Docherty, Jim van Os, Nese Direk, Lina Martinsson, Maria Arranz, Christel M. Middeldorp, Stefan Kloiber, Sintia Iole Belangero, Eske M. Derks, Ingrid Melle, Erlend Bøen, Jan Haavik, Federica Piras, Unna N. Danner, Anil K. Malhotra, Gerome Breen, Stephen V. Faraone, Amanda B Zheutlin, Timothy Poterba, Stephan Ruhrmann, Inge Joa, Ulrik Fredrik Malt, Sarah E. Bergen, Federica Tozzi, Lauren A. Weiss, Hana Papezova, Dominic Holland, Elliot S. Gershon, Jaakko Kaprio, Merete Nordentoft, Scott D. Gordon, Christopher Pittenger, Keun-Ah Cheon, Jennifer Jordan, Philip Gorwood, Myrna M. Weissman, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Isobel Heyman, Eun-Young Shin, Christie L. Burton, Katherine Gordon-Smith, Sietske G. Helder, Peter Nagy, Till F. M. Andlauer, Yunpeng Wang, Young Key Kim, Kate Langley, Søren Dalsgaard, Richard Delorme, Torbjørn Elvsåshagen, Bennett L. Leventhal, Giovanni Gambaro, Christos Androutsos, Jennifer Tübing, Marion Roberts, Annelie Nordin Adolfsson, Hakon Hakonarson, Dorothy E. Grice, Vaughan J. Carr, Konstantinos Tziouvas, Stephanie Zerwas, Cathy L. Barr, Michael Conlon O'Donovan, Per Qvist, Beate St Pourcain, Samuel Kuperman, Leila Karhunen, Jack Samuels, Markus M. Nöthen, Martien J H Kas, Alfonso Tortorella, Mikael Landén, Jennifer Crosbie, Marco A. Grados, Joanna M. Biernacka, Paul D. Arnold, Irene A. Malaty, Jurjen J. Luykx, Nicholas Bass, Naomi R. Wray, Catharina A. Hartman, Christina M. Hultman, Michael S. Okun, Brandon Wormley, Michael Bauer, Daniel J. Smith, Ian Jones, Kathryn Roeder, Brien P. Riley, Caroline M. Nievergelt, Katrin Gade, Sarah Kittel-Schneider, Roy H. Perlis, James R. Mitchell, Ziarih Hawi, James Lee, Liz Forty, William E. Bunney, Thomas Damm Als, Catherine Schaefer, Digby Quested, Matteo Cassina, Anna C. Koller, Patrick Turley, Agnes A. Steixner, Anu Raevuori, Assen Jablensky, Peter Holmans, Dong-Ho Song, S. Evelyn Stewart, Jan K. Buitelaar, Fernando S. Goes, Alexander Münchau, Ayman H. Fanous, Nicolas Ramoz, James B. Potash, Monica Gratacos Mayora, Tobias Banaschewski, Céline S. Reinbold, Renata Rizzo, Arianna Di Florio, Lenka Foretova, Gianfranco Spalletta, Aarno Palotie, Eleftheria Zeggini, Lawrence W. Brown, Julie K. O'Toole, Lynn E. DeLisi, Ulrich Schall, Mary Roberson, Barbara J. Coffey, Bryan J. Mowry, Murray J. Cairns, Dan J. Stein, Glyn Lewis, Marta Ribasés, C. Robert Cloninger, Bettina Konte, John B. Vincent, Duncan S. Palmer, Radhika Kandaswamy, Christine Ladd-Acosta, Lars Alfredsson, Frank Visscher, Ulrike Schmidt, Aiden Corvin, Susan L. Santangelo, Brenda W.J.H. Penninx, David J. Porteous, Tetsuya Ando, Arne E. Vaaler, Bru Cormand, Laura Carlberg, Claire Churchhouse, Manfred Stuhrmann, Niamh Mullins, Christine Søholm Hansen, Cathy L. Budman, Hartmut Imgart, Dan E. Arking, James J. McGough, Michael Gill, Christel Depienne, Roland Burghardt, Antonio Julià, Anders M. Dale, Sven Sandin, Katharina Domschke, Maria Grigoroiu-Serbanescu, Susana Jiménez-Murcia, Marianne Giørtz Pedersen, Zsanett Tarnok, Gisli Baldursson, Michele T. Pato, David M. Hougaard, Thorgeir E. Thorgeirsson, Katharina Bey, Kerstin J. Plessen, Margaret A. Richter, Ole A. Andreassen, Claudine Laurent-Levinson, Leonid Padyukov, Jacques Mallet, Daniela Degortes, John R. Kelsoe, Robert D. Levitan, Andreas Reif, Chaim Huyser, Derek W. Morris, Sina Wanderer, William Byerley, Edna Grünblatt, E.J.C. de Geus, Hyejung Won, Josephine Elia, Rudolf Uher, Jay A. Tischfield, Andreas Karwautz, Gustavo Turecki, Pieter J. Hoekstra, Dorret I. Boomsma, Jacob Rosenthal, Daniele Cusi, Michael C. Neale, Sara Mostafavi, Gwyneth Zai, F. Anthony O'Neill, Gary Donohoe, Karola Rehnström, Harry Brandt, Helena Gaspar, Francis J. McMahon, H-Erich Wichmann, Andrew W. Bergen, Giovanni Coppola, Lea K. 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P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.
Subjects: Netherlands Twin Register (NTR), cross-disorder genetics, Medizin, Genome-wide association study, Tourette syndrome, functional genomics, gene expression, genetic architecture, genetic correlation, GWAS, neurodevelopment, pleiotropy, psychiatric disorders, Psychiatric genetics, 0302 clinical medicine, Pleiotropy, functional genomic, WIDE ASSOCIATION, cross-disorder genetic, 0303 health sciences, Mental Disorders, Genetic Pleiotropy, HUMAN BRAIN, INSIGHTS, Autism spectrum disorder, Schizophrenia, DISEASES, GENETIC CORRELATIONS, medicine.medical_specialty, Neurogenesis, Quantitative Trait Loci, BF, Biology, GENOTYPE IMPUTATION, Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics, Article, General Biochemistry, Genetics and Molecular Biology, psychiatric disorder, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, TRANSCRIPTOME, Psychiatry, 030304 developmental biology, Gwas, Psychiatric Genetics, Cross-disorder Genetics, Functional Genomics, Gene Expression, Genetic Architecture, Genetic Correlation, Neurodevelopment, Psychiatric Disorders, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], IDENTIFICATION, MUTATIONS, medicine.disease, Genetic architecture, DEMETHYLASE, RC0321, 1182 Biochemistry, cell and molecular biology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
Published: 2019

47. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Author: Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, Cearns, Micah, Heilbronner, Urs, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hsu, Yi Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jiménez, Esther, Kahn, Jean Pierre, Kassem, Layla, Kuo, Po Hsiu, Kato, Tadafumi, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan L., Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Ösby, Urban, Pfennig, Andrea, Potash, James B., Reif, Andreas, Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Blackwood, Douglas H.R., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane varregaard, Clarke, Toni Kim, Coleman, Jonathan R.I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Hickie, Ian B., Homuth, Georg, Horn, Carsten, Hottenga, Jouke Jan, Hougaard, David M., Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Dannlowski, Udo, de Geus, E. J.C., Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Veeh, Julia, Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, McMahon, Francis J., APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, APH - Digital Health, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Jamain, Stéphane, University of Adelaide, South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), Mental Health Services [Adelaide, SA, Australia], National Institute of Mental Health (NIMH), Ludwig Maximilian University [Munich] (LMU), Georg-August-University = Georg-August-Universität Göttingen, Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard Medical School [Boston] (HMS), Harvard School of Public Health, University of California [San Diego] (UC San Diego), University of California (UC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Dokkyo Medical University, Università degli Studi di Cagliari = University of Cagliari (UniCa), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain] (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], Geneva University Hospital (HUG), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Karl-Franzens-Universität Graz, Mayo Clinic [Rochester], McGill University Health Center [Montreal] (MUHC), National Taiwan University [Taiwan] (NTU), University Hospital Basel [Basel], Poznan University of Medical Sciences [Poland] (PUMS), Johns Hopkins University (JHU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Basel (Unibas), Neuroscience Research Australia [Sydney, NSW, Australia] (NRA), University of New South Wales [Sydney] (UNSW), Psychiatrie de l'enfant et de l'adolescent [CH C. Perrens, Bordeaux], SECOP - centre hospitalier Charles Perrens, Dalhousie University [Halifax], 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry [Bucharest, Romania], Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], Osaka University [Osaka], Graduate School of Medicine [Osaka], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Psychiatrie et Psychologie Clinique de Liaison [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Psychothérapique de Nancy (CPN), National Institutes of Health [Bethesda] (NIH), Environmental Molecular Biology Laboratory (RIKEN), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Goethe-University Frankfurt am Main, Landesklinikum Neunkirchen (LK Neunkirchen), Hokkaido University Graduate School of Medicine [Sapporo, Japan], Sahlgrenska Academy at University of Gothenburg [Göteborg], Research Service VA San Diego Healthcare System, Università degli Studi di Perugia = University of Perugia (UNIPG), University of Cincinnati (UC), IMIM-Hospital del Mar, Generalitat de Catalunya, Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft, University of Salerno (UNISA), University of the Study of Campania Luigi Vanvitelli, National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Nagoya University Graduate School of Medicine [Japon], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Medical University Graz, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Sigmund Freud University (SFU), Douglas Mental Health University Institute [Montréal], University of Heidelberg, Medical Faculty, Black Dog Institute [Sydney, Australia], Johns Hopkins Bloomberg School of Public Health [Baltimore], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, The Florey Institute of Neuroscience and Mental Health [Parkville, VIC, Australie], University of Melbourne, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium: Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till F M Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T F Beekman, Tim B Bigdeli, Elisabeth B Binder, Douglas H R Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Varregaard Christensen, Toni-Kim Clarke, Jonathan R I Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A Lind, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant C B Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E J C de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela A F Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan., Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Georg-August-University [Göttingen], University of California, Universita degli Studi di Cagliari [Cagliari], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Graz, Università degli Studi di Perugia (UNIPG), University of Münster, Karl-Franzens-Universität [Graz, Autriche], Amare, A. T., Schubert, K. O., Hou, L., Clark, S. R., Papiol, S., Cearns, M., Heilbronner, U., Degenhardt, F., Tekola-Ayele, F., Hsu, Y. -H., Shekhtman, T., Adli, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Brichant-Petitjean, C., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Del Zompo, M., Depaulo, J. R., Etain, B., Jamain, S., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Herms, S., Hoffmann, P., Hofmann, A., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J. R., Kittel-Schneider, S., Kliwicki, S., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Tortorella, A., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S. L., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Pfennig, A., Potash, J. B., Reif, A., Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., Agerbo, E., Air, T. M., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bigdeli, T. B., Binder, E. B., Blackwood, D. H. R., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J., Clarke, T. -K., Coleman, J. R. I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G. E., Davies, G., Deary, I. J., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Kiadeh, F. F. H., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Gordon, S. D., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Ising, M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Krogh, J., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Mcgrath, P., Mcguffin, P., Medland, S. E., Mehta, D., Middeldorp, C. M., Mihailov, E., Milaneschi, Y., Milani, L., Montgomery, G. W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Owen, M. J., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Pettersson, E., Peyrot, W. J., Pistis, G., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Rivera, M., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Shi, J., Shyn, S. I., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., Van der Auwera, S., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Witt, S. H., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Baune, B. T., Berger, K., Boomsma, D. I., Dannlowski, U., de Geus, E. J. C., Domenici, E., Domschke, K., Esko, T., Grabe, H. J., Hamilton, S. P., Hayward, C., Heath, A. C., Kendler, K. S., Kloiber, S., Lewis, G., Li, Q. S., Lucae, S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Mortensen, P. B., Muller-Myhsok, B., Nordentoft, M., O'Donovan, M. C., Paciga, S. A., Pedersen, N. L., Penninx, B. W. J. H., Perlis, R. H., Porteous, D. J., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T. G., Smoller, J. W., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M. M., Werge, T., Lewis, C. M., Levinson, D. F., Breen, G., Borglum, A. D., Sullivan, P. F., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Maj, M., Turecki, G., Vieta, E., Veeh, J., Wright, A., Zandi, P. P., Mitchell, P. B., Bauer, M., Alda, M., Mcmahon, F. J., and Adult Psychiatry
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Lithium (medication), [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Genome-wide association study, Logistic regression, THERAPY, ddc:616.89, 0302 clinical medicine, Medicine, Major depression, PREDICTORS, Depression (differential diagnoses), RISK, Depression, Psychiatry and Mental health, Quartile, Cohort, AUGMENTATION, medicine.drug, POLARITY, medicine.medical_specialty, GENETICS, Bipolar disorder, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Lithium, PROPHYLACTIC LITHIUM, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Internal medicine, Humans, ddc:610, AGENTS, Molecular Biology, Genetic association, Depressive Disorder, Major, business.industry, medicine.disease, EFFICACY, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, PHARMACOLOGICAL-TREATMENTS, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
Published: 2021

48. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Author: Michael McCarthy, Claire O'Donovan, Urs Heilbronner, Ichiro Kusumi, Eduard Vieta, Liping Hou, Hsi-Chung Chen, Claire Slaney, Maria Grigoroiu-Serbanescu, Kazufumi Akiyama, Michael Bauer, Janusz K. Rybakowski, Frank Bellivier, Marion Leboyer, Katzutaka Shimoda, Palmiero Monteleone, Cristiana Cruceanu, Alessio Squassina, Stephanie H. Witt, Tadafumi Kato, Giovanni Severino, Alfonso Tortorella, J. Raymond DePaulo, Martin Alda, Louise Frisén, Mazda Adl, Martin Schalling, Per Hoffmann, Susan G. Leckband, Jean-Pierre Kahn, Jean-Michel Aubry, Francis J. McMahon, Sven Cichon, Alexandre Dayer, Tatyana Shekhtman, Franziska Degenhardt, James B. Potash, Bruno Etain, Joseph Frank, Antonio Benabarre, Bernhard T. Baune, Gloria Roberts, Ryota Hashimoto, Tomas Novak, Paul D. Shilling, Julia Veeh, Joanna M. Biernacka, Barbara König, Peter Falkai, Philip B. Mitchell, Urban Ösby, Esther Jiménez, Sébastien Gard, Mark A. Frye, Sarah Kittel-Schneider, Layla Kassem, Fasil Tekola-Ayele, Armin Birner, Cynthia Marie-Claire, Raffaella Ardau, Abesh Kumar Bhattacharjee, Stéphane Jamain, Julie Garnham, Guy A. Rouleau, Caterina Chillotti, Piotr M. Czerski, Thomas G. Schulze, Gustavo Turecki, Anbupalam Thalamuthu, Claudia Pisanu, Azmeraw T. Amare, Marina Mitjans, Sergi Papiol, Mario Maj, Bárbara Arias, Janice M. Fullerton, Nina Dalkner, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Francis M. Mondimore, Eva Z. Reininghaus, Fernando S. Goes, Lena Backlund, Francesc Colom, Catharina Lavebratt, Christian Simhandl, Marcella Rietschel, Micah Cearns, Mikael Landén, Norio Ozaki, Gonzalo Laje, Barbara W. Schweizer, Nirmala Akula, Andrea Pfennig, Yi-Hsiang Hsu, John R. Kelsoe, Lina Martinsson, Markus M. Nöthen, Caroline M. Nievergelt, Pavla Stopkova, Mirko Manchia, Susan L. McElroy, Peter P. Zandi, Scott R. Clark, Joanna Hauser, Andreas J. Forstner, Po-Hsiu Kuo, Andreas Reif, Maria Del Zompo, Paul Grof, Fabian Streit, Ewa Ferensztajn-Rochowiak, Pablo Cervantes, Thomas Stamm, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Digital Health, Schubert, K. O., Thalamuthu, A., Amare, A. T., Frank, J., Streit, F., Adl, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Marie-Claire, C., Cearns, M., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Clark, S. R., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Etain, B., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Heilbronner, U., Herms, S., Hoffmann, P., Hou, L., Hsu, Y. -H., Jamain, S., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J., Kittel-Schneider, S., Ferensztajn-Rochowiak, E., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Maj, M., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Papiol, S., Pfennig, A., Pisanu, C., Potash, J. B., Reif, A., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shekhtman, T., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Tekola-Ayele, F., Tortorella, A., Turecki, G., Veeh, J., Vieta, E., Witt, S. H., Roberts, G., Zandi, P. P., Alda, M., Bauer, M., Mcmahon, F. J., Mitchell, P. B., Schulze, T. G., Rietschel, M., and Baune, B. T.
Subjects: Oncology, Multifactorial Inheritance, Treatment response, medicine.medical_specialty, Lithium (medication), Bipolar disorder, Poor responder, Neurosciences. Biological psychiatry. Neuropsychiatry, Lithium, DISEASE, Article, Cellular and Molecular Neuroscience, Risk Factors, Internal medicine, medicine, Humans, Manic-depressive illness, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Depressió psíquica, METAANALYSIS, Biological Psychiatry, Depression (differential diagnoses), MANIA, Depressive Disorder, Depressive Disorder, Major, Trastorn bipolar, Depression, business.industry, Major, medicine.disease, Pathway analysis, Liti, COMPARATIVE EFFICACY, Psychiatry and Mental health, Mental depression, Schizophrenia, Polygenic risk score, Esquizofrènia, Pharmacogenomics, business, RC321-571, medicine.drug
Abstract: Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
Published: 2021

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

Author: Andlauer, Till F M, Guzman-Parra, Jose, Orozco Diaz, Guillermo, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, de Diego-Otero, Yolanda, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Parra, José Guzman, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Moreno-Küstner, Berta, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, Juréus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L, Auburger, Georg, Kittel-Schneider, Sarah, Knowles, James A, Kogevinas, Manolis, Koller, Anna C, Kupka, Ralph, Lavebratt, Catharina, Lawrence, Jacob, Lawson, William B, Leber, Markus, Lee, Phil H, Degenhardt, Franziska, Levy, Shawn E, Li, Jun Z, Liu, Chunyu, Lucae, Susanne, Maaser, Anna, MacIntyre, Donald J, Mahon, Pamela B, Maier, Wolfgang, Martinsson, Lina, McCarroll, Steve, Heilmann-Heimbach, Stefanie, McGuffin, Peter, McInnis, Melvin G, McKay, James D, Medeiros, Helena, Medland, Sarah E, Meng, Fan, Milani, Lili, Montgomery, Grant W, Morris, Derek W, Mühleisen, Thomas W, Mullins, Niamh, Nguyen, Hoang, Nievergelt, Caroline M, Adolfsson, Annelie Nordin, Nwulia, Evaristus A, O'Donovan, Claire, Loohuis, Loes M Olde, Ori, Anil P S, Oruc, Lilijana, Ösby, Urban, Perlis, Roy H, Perry, Amy, Pfennig, Andrea, Potash, James B, Purcell, Shaun M, Regeer, Eline J, Reif, Andreas, Reinbold, Céline S, Rice, John P, Richards, Alexander L, Frank, Josef, Rivas, Fabio, Rivera, Margarita, Roussos, Panos, Ruderfer, Douglas M, Ryu, Euijung, Sánchez-Mora, Cristina, Schatzberg, Alan F, Scheftner, William A, Schork, Nicholas J, Weickert, Cynthia Shannon, Foo, Jerome C, Shehktman, Tatyana, Shilling, Paul D, Sigurdsson, Engilbert, Slaney, Claire, Smeland, Olav B, Sobell, Janet L, Hansen, Christine Søholm, Spijker, Anne T, Clair, David St, Steffens, Michael, Streit, Fabian, Treutlein, Jens, Strauss, John S, Strohmaier, Jana, Szelinger, Szabolcs, Thompson, Robert C, EThorgeirsson, Thorgeir, Vedde, Helmut, Wang, Weiqing, Watson, Stanley J, Witt, Stephanie H, Weickert, Thomas W, Xi, Simon, Xu, Wei, Young, Allan H, Zandi, Peter, Zhang, Peng, Zollner, Sebastian, Adolfsson, Rolf, Agartz, Ingrid, Cichon, Sven, Alda, Martin, Backlund, Lena, Baune, Bernhard T, Bellivier, Frank, Berrettini, Wade H, Biernacka, Joanna M, Blackwood, Douglas H R, Boehnke, Michael, Børglum, Anders D, Corvin, Aiden, Craddock, Nicholas, Daly, Mark J, Dannlowski, Udo, Esko, Tõnu, Etain, Bruno, Frye, Mark, Fullerton, Janice M, Gershon, Elliot S, Gill, Michael, Goes, Fernando, Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Hougaard, David M, Hultman, Christina M, Jones, Ian, Jones, Lisa A, Kahn, René S, Kirov, George, Landén, Mikael, Leboyer, Marion, Mayoral, Fermín, Lewis, Cathryn M, Li, Qingqin S, Lissowska, Jolanta, Martin, Nicholas G, Mayoral, Fermin, McElroy, Susan L, McIntosh, Andrew M, McMahon, Francis J, Melle, Ingrid, Metspalu, Andres, Müller-Myhsok, Bertram, Mitchell, Philip B, Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Myers, Richard M, Neale, Benjamin M, Nimgaonkar, Vishwajit, Nordentoft, Merete, Nöthen, Markus M, Forstner, Andreas J, O'Donovan, Michael C, Oedegaard, Ketil J, Owen, Michael J, Paciga, Sara A, Pato, Carlos, Pato, Michele T, Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Ribasés, Marta, Rietschel, Marcella, Rouleau, Guy A, Schalling, Martin, Schofield, Peter R, Schulze, Thomas G, Serretti, Alessandro, Smoller, Jordan W, Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Sullivan, Patrick F, Turecki, Gustavo, Vaaler, Arne E, Vieta, Eduard, Vincent, John B, Werge, Thomas, Nurnberger, John I, Wray, Naomi R, Florio, Arianna Di, Edenberg, Howard J, Stahl, Eli A, Ophoff, Roel A, Scott, Laura J, Andreassen, Ole A, Kelsoe, John, Sklar, Pamela, Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M, Breen, Gerome, Abdellaoui, Abdel, Adams, Mark J, Agerbo, Esben, Air, Tracy M, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T F, Bigdeli, Tim B, Binder, Elisabeth B, Bryois, Julien, Buttenschøn, Henriette N, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R I, Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, McQuillin, Andrew, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Deary, Ian J, Derks, Eske M, Direk, Nese, Dolan, Conor V, Dunn, Erin C, Eley, Thalia C, Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K, Gaspar, Héléna A, Goes, Fernando S, Trubetskoy, Vassily, Hall, Lynsey S, Hansen, Thomas F, Hickie, Ian B, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Howard, David M, Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Kohane, Isaac S, Kraft, Julia, Wang, Yunpeng, Kretzschmar, Warren W, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A, MacKinnon, Dean F, Maier, Robert M, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Mondimore, Francis M, Mostafavi, Sara, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, O'Reilly, Paul F, Oskarsson, Hogni, Painter, Jodie N, González, Maria José, de Leeuw, Christiaan A, Pedersen, Carsten Bøcker, Peterson, Roseann E, Pettersson, Erik, Peyrot, Wouter J, Pistis, Giorgio, Quiroz, Jorge A, Qvist, Per, Steinberg, Stacy, Riley, Brien P, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Shi, Jianxin, Shyn, Stanley I, Sinnamon, Grant C B, Pavlides, Jennifer M Whitehead, Smit, Johannes H, Smith, Daniel J, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Thorgeirsson, Thorgeir E, Traylor, Matthew, Uitterlinden, André G, Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M, Viktorin, Alexander, Pers, Tune H, Visscher, Peter M, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Wu, Yang, Xi, Hualin S, Yang, Jian, Holmans, Peter A, Zhang, Futao, Arolt, Volker, Berger, Klaus, Boomsma, Dorret I, de Geus, E. J. C., DePaulo, J Raymond, Domenici, Enrico, Abbott, Liam, Domschke, Katharina, Grabe, Hans J, Hamilton, Steven P, Hayward, Caroline, Heath, Andrew C, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Madden, Pamela A F, Magnusson, Patrik K, Akil, Huda, Pedersen, Nancy L, Penninx, Brenda W J H, Porteous, David J, Preisig, Martin, Albani, Diego, Schaefer, Catherine, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M, Gil Flores, Susana, Alliey-Rodriguez, Ney, Levinson, Douglas F, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Cabaleiro Fabeiro, Francisco J, Belliveau, Richard, Bergen, Sarah E, Bøen, Erlend, Boks, Marco, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Del Río Noriega, Francisco, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Coryell, William, Perez, Fermin Perez, Craig, David W, Cruceanu, Cristiana, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Del-Favero, Jurgen, Djurovic, Srdjan, Dobbyn, Amanda L, Haro González, Jesus, Dumont, Ashley, Elvsåshagen, Torbjørn, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Fraser, Christine, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Epidemiology and Data Science, APH - Digital Health, Andlauer T.F.M., Guzman-Parra J., Streit F., Strohmaier J., Gonzalez M.J., Gil Flores S., Cabaleiro Fabeiro F.J., del Rio Noriega F., Perez F.P., Haro Gonzalez J., Orozco Diaz G., de Diego-Otero Y., Moreno-Kustner B., Auburger G., Degenhardt F., Heilmann-Heimbach S., Herms S., Hoffmann P., Frank J., Foo J.C., Treutlein J., Witt S.H., Cichon S., Kogevinas M., Stahl E.A., Breen G., Forstner A.J., McQuillin A., Ripke S., Trubetskoy V., Mattheisen M., Wang Y., Coleman J.R.I., Gaspar H.A., de Leeuw C.A., Steinberg S., Pavlides J.M.W., Trzaskowski M., Pers T.H., Holmans P.A., Abbott L., Agerbo E., Akil H., Albani D., Alliey-Rodriguez N., Als T.D., Anjorin A., Antilla V., Awasthi S., Badner J.A., Baekvad-Hansen M., Barchas J.D., Bass N., Bauer M., Belliveau R., Bergen S.E., Pedersen C.B., Boen E., Boks M., Boocock J., Budde M., Bunney W., Burmeister M., Bybjerg-Grauholm J., Byerley W., Casas M., Cerrato F., Cervantes P., Chambert K., Charney A.W., Chen D., Churchhouse C., Clarke T.-K., Coryell W., Craig D.W., Cruceanu C., Czerski P.M., Dale A.M., de Jong S., Del-Favero J., DePaulo J.R., Djurovic S., Dobbyn A.L., Dumont A., Elvsashagen T., Escott-Price V., Fan C.C., Fischer S.B., Flickinger M., Foroud T.M., Forty L., Fraser C., Freimer N.B., Frisen L., Gade K., Gage D., Garnham J., Giambartolomei C., Pedersen M.G., Goldstein J., Gordon S.D., Gordon-Smith K., Green E.K., Green M.J., Greenwood T.A., Grove J., Guan W., Parra J.G., Hamshere M.L., Hautzinger M., Heilbronner U., Hipolito M., Holland D., Huckins L., Jamain S., Johnson J.S., Jureus A., Kandaswamy R., Karlsson R., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Koller A.C., Kupka R., Lavebratt C., Lawrence J., Lawson W.B., Leber M., Lee P.H., Levy S.E., Li J.Z., Liu C., Lucae S., Maaser A., MacIntyre D.J., Mahon P.B., Maier W., Martinsson L., McCarroll S., McGuffin P., McInnis M.G., McKay J.D., Medeiros H., Medland S.E., Meng F., Milani L., Montgomery G.W., Morris D.W., Muhleisen T.W., Mullins N., Nguyen H., Nievergelt C.M., Adolfsson A.N., Nwulia E.A., O'Donovan C., Loohuis L.M.O., Ori A.P.S., Oruc L., Osby U., Perlis R.H., Perry A., Pfennig A., Potash J.B., Purcell S.M., Regeer E.J., Reif A., Reinbold C.S., Rice J.P., Richards A.L., Rivas F., Rivera M., Roussos P., Ruderfer D.M., Ryu E., Sanchez-Mora C., Schatzberg A.F., Scheftner W.A., Schork N.J., Weickert C.S., Shehktman T., Shilling P.D., Sigurdsson E., Slaney C., Smeland O.B., Sobell J.L., Hansen C.S., Spijker A.T., Clair D.S., Steffens M., Strauss J.S., Szelinger S., Thompson R.C., EThorgeirsson T., Vedde H., Wang W., Watson S.J., Weickert T.W., Xi S., Xu W., Young A.H., Zandi P., Zhang P., Zollner S., Adolfsson R., Agartz I., Alda M., Backlund L., Baune B.T., Bellivier F., Berrettini W.H., Biernacka J.M., Blackwood D.H.R., Boehnke M., Borglum A.D., Corvin A., Craddock N., Daly M.J., Dannlowski U., Esko T., Etain B., Frye M., Fullerton J.M., Gershon E.S., Gill M., Goes F., Grigoroiu-Serbanescu M., Hauser J., Hougaard D.M., Hultman C.M., Jones I., Jones L.A., Kahn R.S., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Martin N.G., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Metspalu A., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Muller-Myhsok B., Myers R.M., Neale B.M., Nimgaonkar V., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Owen M.J., Paciga S.A., Pato C., Pato M.T., Posthuma D., Ramos-Quiroga J.A., Ribases M., Rietschel M., Rouleau G.A., Schalling M., Schofield P.R., Schulze T.G., Serretti A., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Werge T., Nurnberger J.I., Wray N.R., Florio A.D., Edenberg H.J., Ophoff R.A., Scott L.J., Andreassen O.A., Kelsoe J., Sklar P., Byrne E.M., Abdellaoui A., Adams M.J., Air T.M., Bacanu S.-A., Beekman A.T.F., Bigdeli T.B., Binder E.B., Bryois J., Buttenschon H.N., Cai N., Castelao E., Christensen J.H., Colodro-Conde L., Couvy-Duchesne B., Crawford G.E., Davies G., Deary I.J., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Kiadeh F.F.H., Finucane H.K., Goes F.S., Hall L.S., Hansen T.F., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Howard D.M., Ising M., Jansen R., Jorgenson E., Kohane I.S., Hill, Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacKinnon D.F., Maier R.M., Marchini J., Mbarek H., McGrath P., Mehta D., Middeldorp C.M., Mihailov E., Milaneschi Y., Mondimore F.M., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Painter J.N., Peterson R.E., Pettersson E., Peyrot W.J., Pistis G., Quiroz J.A., Qvist P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Shi J., Shyn S.I., Sinnamon G.C.B., Smit J.H., Smith D.J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Uitterlinden A.G., Umbricht D., Van der Auwera S., van Hemert A.M., Viktorin A., Visscher P.M., Webb B.T., Weinsheimer S.M., Wellmann J., Willemsen G., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Berger K., Boomsma D.I., de Geus E.J.C., Domenici E., Domschke K., Grabe H.J., Hamilton S.P., Hayward C., Heath A.C., Kendler K.S., Kloiber S., Lewis G., Madden P.A.F., Magnusson P.K., Pedersen N.L., Penninx B.W.J.H., Porteous D.J., Preisig M., Schaefer C., Tiemeier H., Uher R., Volzke H., Weissman M.M., Levinson D.F., Child and Adolescent Psychiatry / Psychology, Epidemiology, Internal Medicine, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, and Adult Psychiatry
Subjects: Netherlands Twin Register (NTR), Genetic variants, Bipolar Disorder, Specific risk, Disease, 0302 clinical medicine, Multiplex, Genetic risk, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Depression (differential diagnoses), 0303 health sciences, Depression, ddc, 3. Good health, Geðraskanir, Psychiatry and Mental health, Schizophrenia, Cohort, Major depressive disorder, Case-Control Studie, Human, medicine.medical_specialty, Bipolar disorder, Article, Cellular and Molecular Neuroscience, 03 medical and health sciences, Geðklofi, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Psychiatry, Þunglyndi, Molecular Biology, 030304 developmental biology, Depressive Disorder, Major, Geðhvarfasýki, business.industry, Psychiatric disorder, medicine.disease, Genarannsóknir, Case-Control Studies, Multiple comparisons problem, business, 030217 neurology & neurosurgery
Abstract: Publisher's version, Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development., The study was supported by the German Federal Ministry of Education and Research (BMBF), through the Integrated Network IntegraMent, under the auspices of the e:Med programme (grants 01ZX1314A to MMN and SC; 01ZX1314G to MR; 01ZX1614J to BMM) through grants 01EE1406C to MR and 01EE1409C to MR and SHW, and through ERA-NET NEURON, “SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation” (01EW1810 to MR) and BMBF grants 01EE1409C and 01EE1406C to MR and SHW; by the German Research Foundation (DFG grants FOR2107; RI908/11-2 to MR; NO246/10-2 to MMN; MU1315/8-2 to BMM; WI 3439/3-2 to SHW), by the Andalusian regional Health and Innovation Government (grants PI-0060-2017, RC-0006-2015 the Nicolas Monarde Programme for YDO and CTS-546) and by the Swiss National Science Foundation (SNSF grant 156791 to SC). MMN is a member of the DFG-funded cluster of excellence ImmunoSensation. The PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320). We thank the research participants and employees of 23andMe, Inc. for their contribution to the MDD meta-analysis published in [14]. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for the present analyses. See the Supplementary Data for extended Acknowledgements.
Published: 2021

50. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author: James McKay, Frank Bellivier, Mark A. Frye, Bertram Müller-Myhsok, Fermín Mayoral, I. Nicol Ferrier, Marion Leboyer, Fabian Streit, Dan J. Stein, James L. Kennedy, Christine Søholm Hansen, Scott D. Gordon, Beata Świątkowska, Valentina Escott-Price, Michael Bauer, Lina Martinsson, Donald J. MacIntyre, Oleksandr Frei, Daniel J. Smith, Sara A. Paciga, Takeo Saito, Jennifer L. Moran, Verneri Antilla, C Pantelis, Tomas Olsson, Swapnil Awasthi, Lena Backlund, Eirini Maratou, Martin Schalling, John B. Vincent, Niamh Mullins, Sarah E. Bergen, Niamh L. O'Brien, Marco P. Boks, Carsten Bøcker Pedersen, Mikael Landén, Franziska Degenhardt, Hang Zhou, Margarita Rivera, Andrew M. McIntosh, Manuel Mattheisen, Shawn Levy, Roy H. Perlis, John P. Rice, Sigurdur H. Magnusson, Amanda Dobbyn, Michael Conlon O'Donovan, Julien Bryois, Wolfgang Maier, John-Anker Zwart, J. Raymond DePaulo, Martin Alda, Laura G. Sloofman, Friederike Sophie David, James A. Knowles, Aiden Corvin, Thomas G. Schulze, Markus M. Nöthen, Nolan Kamitaki, Nina Dalkner, Brandon J. Coombes, Gustavo Turecki, Allan H. Young, Caroline M. Nievergelt, Patricia T. Michie, Ingrid Agartz, Towfique Raj, Diego Albani, Maria Grigoroiu-Serbanescu, Bernhard T. Baune, Kyooseob Ha, Vincent Millischer, Engilbert Sigurdsson, Eva C. Beins, Nicholas G. Martin, Gulja Babadjanova, Josef Frank, Eva Z. Reininghaus, Patrick F. Sullivan, Ian R. Gizer, Guy A. Rouleau, Carmel M. Loughland, Christine Lochner, Thorsten M. Kranz, Amy Perry, Arne E. Vaaler, Mariam M. Al Eissa, Simon Xi, Claire O'Donovan, Josep Antoni Ramos-Quiroga, Ketil J. Oedegaard, Helmut Vedder, Carol A. Mathews, Panagiotis Ferentinos, Tim B. Bigdeli, Derek W. Morris, Per Hoffmann, Mark Hyman Rapaport, Peter P. Zandi, Michael John Owen, Douglas M. Ruderfer, Anders D. Børglum, Catharina Lavebratt, Thorgeir E. Thorgeirsson, Paul A. Tooney, Michiaki Kubo, Steven A. Kushner, Jan Hillert, Loes M. Olde Loohuis, Anastasia Antoniou, Murielle Brum, Chikashi Terao, Nathaniel W. McGregor, Fabio Rivas, James B. Potash, Kevin S. O’Connell, Susanne Lucae, Brian M. Schilder, Katrin Gade, Stephan Ripke, Kristina Adorjan, Kari Stefansson, Tiffany A. Greenwood, Panos Roussos, Sarah Kittel-Schneider, Steven A. McCarroll, Sergi Papiol, Heon Jeong Lee, Assen Jablensky, Liliya Abramova, Dennis Hellgren, Jonas Bybjerg-Grauholm, Martin Lundberg, Hong-Hee Won, William Byerley, Lars Alfredsson, Joel Gelernter, Andrew McQuillin, Claire Slaney, Marta Ribasés, Stephanie H. Witt, Yoichiro Kamatani, Kyung Sue Hong, Marie Bækvad-Hansen, María Soler Artigas, Julie M. Cunningham, Fanny Senner, Stacy Steinberg, Paul D. Shilling, Nakao Iwata, Eystein Stordal, Armin Birner, Sarah E. Medland, Miquel Casas, Ben Michael Brumpton, Erlend Bøen, Bryan J. Mowry, Jolanta Lissowska, Francis J. McMahon, Howard J. Edenberg, Grant W. Montgomery, John I. Nurnberger, Stéphane Jamain, Claudio Toma, Ney Alliey-Rodriguez, Ole Mors, Micha Gawlik, David Curtis, Catrin Lewis, Evangelia-Eirini Tsermpini, Georgia Panagiotaropoulou, Marcella Rietschel, Jessica Yang, Ian Jones, Eduard Vieta, Ole A. Andreassen, Richard M. Myers, Dimitris Dikeos, Melissa J. Green, Janet L. Sobell, Maria Koromina, Piotr M. Czerski, Lilijana Oruc, Sven Cichon, Udo Dannlowski, Bruno Etain, Monika Budde, Alessia Fiorentino, Naomi R. Wray, Qingqin S. Li, Murray J. Cairns, Jonathan R. I. Coleman, Jose Guzman-Parra, Andreas J. Forstner, Hannah Young, Alfredo B. Cuellar-Barboza, Julian Roth, Torbjørn Elvsåshagen, Zhen Qiao, Thomas Werge, Athanassios Douzenis, Cristiana Cruceanu, Rolf Adolfsson, Peter Holmans, Vaughan J. Carr, Thomas W. Weickert, Masashi Ikeda, Joanna M. Biernacka, Lea Sirignano, Adam X. Maihofer, Ralph W. Kupka, John Strauss, Anders M. Dale, Elliot S. Gershon, Jakob Grove, Arianna Di Florio, Helena Medeiros, Ingrid Melle, Preben Bo Mortensen, Kristi Krebs, Saskia P. Hagenaars, Liz Forty, Stanley V. Catts, David M. Hougaard, Marianne Giørtz Pedersen, Andreas Reif, Toni-Kim Clarke, Anne T. Spijker, Danielle Posthuma, Manolis Kogevinas, Michael Boehnke, Rosa Bosch, Gerome Breen, Benjamin M. Neale, Jessica S. Johnson, Katherine Gordon-Smith, Cristina Sánchez-Mora, Alexander W. Charney, Henry R. Kranzler, Digby Quested, René S. Kahn, Lili Milani, Merete Nordentoft, Nathalie Brunkhorst-Kanaan, Laura M. Huckins, James T.R. Walters, Sigrid Børte, Antonio F. Pardiñas, Kristian Hveem, Julie Garnham, Jacob Lawrence, Vassily Trubetskoy, Rodney J. Scott, Nicholas Bass, Carlos N. Pato, Andrea Pfennig, Wei Xu, Calwing Liao, Nicholas John Craddock, Thomas Damm Als, Christina M. Hultman, Fernando S. Goes, Adebayo Anjorin, Evgenia Porichi, Frans Henskens, Nelson B. Freimer, Janice M. Fullerton, Cathryn M. Lewis, Srdjan Djurovic, Roel A. Ophoff, Phil Lee, Peter McGuffin, Gunnar Morken, George P. Patrinos, Alessandro Serretti, Cynthia Shannon Weickert, Pablo Cervantes, Bendik S. Winsvold, Tatiana Foroud, Tõnu Esko, Ulrich Schall, Michele T. Pato, Ji Hyun Baek, John R. Kelsoe, Olav B. Smeland, Janos Kalman, Eva C. Schulte, Joanna Hauser, Urs Heilbronner, Magnús Haraldsson, Martin Hautzinger, Lea Zillich, Eline J. Regeer, Douglas Blackwood, Laura J. Scott, Jordan W. Smoller, Michael J. Gandal, Marquis P. Vawter, Philip B. Mitchell, Ole Kristian Drange, Peter R. Schofield, Susanne Bengesser, Stefan Herms, George Kirov, Markus Leber, Louise Frisén, Thomas W. Mühleisen, Susan L. McElroy, Irwin D. Waldman, Wade H. Berrettini, Sally I. Sharp, Minsoo Kim, Lisa Jones, Eli A. Stahl, Hreinn Stefansson, Esben Agerbo, Dolores Malaspina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Mullins N., Forstner A.J., O'Connell K.S., Coombes B., Coleman J.R.I., Qiao Z., Als T.D., Bigdeli T.B., Borte S., Bryois J., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Kim M., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Steinberg S., Trubetskoy V., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Agerbo E., Al Eissa M., Albani D., Alliey-Rodriguez N., Anjorin A., Antilla V., Antoniou A., Awasthi S., Baek J.H., Baekvad-Hansen M., Bass N., Bauer M., Beins E.C., Bergen S.E., Birner A., Bocker Pedersen C., Boen E., Boks M.P., Bosch R., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Budde M., Bybjerg-Grauholm J., Byerley W., Cairns M., Casas M., Cervantes P., Clarke T.-K., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Degenhardt F., Djurovic S., Dobbyn A.L., Douzenis A., Elvsashagen T., Escott-Price V., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frank J., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Giortz Pedersen M., Gizer I.R., Gordon S.D., Gordon-Smith K., Greenwood T.A., Grove J., Guzman-Parra J., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Herms S., Hoffmann P., Holmans P.A., Huckins L., Jamain S., Johnson J.S., Kalman J.L., Kamatani Y., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Lawrence J., Leber M., Lee H.-J., Lee P.H., Levy S.E., Lewis C., Liao C., Lucae S., Lundberg M., MacIntyre D.J., Magnusson S.H., Maier W., Maihofer A., Malaspina D., Maratou E., Martinsson L., Mattheisen M., McCarroll S.A., McGregor N.W., McGuffin P., McKay J.D., Medeiros H., Medland S.E., Millischer V., Montgomery G.W., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Potash J.B., Quested D., Raj T., Rapaport M.H., DePaulo J.R., Regeer E.J., Rice J.P., Rivas F., Rivera M., Roth J., Roussos P., Ruderfer D.M., Sanchez-Mora C., Schulte E.C., Senner F., Sharp S., Shilling P.D., Sigurdsson E., Sirignano L., Slaney C., Smeland O.B., Smith D.J., Sobell J.L., Soholm Hansen C., Soler Artigas M., Spijker A.T., Stein D.J., Strauss J.S., Swiatkowska B., Terao C., Thorgeirsson T.E., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Walters J.T.R., Witt S.H., Xi S., Xu W., Yang J.M.K., Young A.H., Young H., Zandi P.P., Zhou H., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Babadjanova G., Backlund L., Baune B.T., Bellivier F., Bengesser S., Berrettini W.H., Blackwood D.H.R., Boehnke M., Borglum A.D., Breen G., Carr V.J., Catts S., Corvin A., Craddock N., Dannlowski U., Dikeos D., Esko T., Etain B., Ferentinos P., Frye M., Fullerton J.M., Gawlik M., Gershon E.S., Goes F.S., Green M.J., Grigoroiu-Serbanescu M., Hauser J., Henskens F., Hillert J., Hong K.S., Hougaard D.M., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Jones I., Jones L.A., Kahn R.S., Kelsoe J.R., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Lochner C., Loughland C., Martin N.G., Mathews C.A., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Michie P., Milani L., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Mowry B., Muller-Myhsok B., Myers R.M., Neale B.M., Nievergelt C.M., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Olsson T., Owen M.J., Paciga S.A., Pantelis C., Pato C., Pato M.T., Patrinos G.P., Perlis R.H., Posthuma D., Ramos-Quiroga J.A., Reif A., Reininghaus E.Z., Ribases M., Rietschel M., Ripke S., Rouleau G.A., Saito T., Schall U., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Scott R.J., Serretti A., Shannon Weickert C., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Streit F., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Waldman I.D., Weickert T.W., Werge T., Wray N.R., Zwart J.-A., Biernacka J.M., Nurnberger J.I., Cichon S., Edenberg H.J., Stahl E.A., McQuillin A., Di Florio A., Ophoff R.A., Andreassen O.A., IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etain, Bruno
Subjects: Multifactorial Inheritance, Bipolar Disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Genome-wide association study, Major Histocompatibility Complex/genetics, Major Histocompatibility Complex, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH: Bipolar Disorder, Chromosomes, Human, Spectrum disorder, Genetics, 0303 health sciences, Bipolar Disorder/genetics, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, Phenotype, Schizophrenia, Synaptic signaling, Case-Control Studie, Human, Quantitative Trait Loci, Biology, MESH: Phenotype, MESH: Chromosomes, Human, Article, 03 medical and health sciences, MESH: Major Histocompatibility Complex, SDG 3 - Good Health and Well-being, ddc:570, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, Multifactorial Inheritance/genetics, MESH: Genome, Human, 030304 developmental biology, MESH: Humans, Genome, Human, Risk Factor, Chromosomes, Human/genetics, Mental illness, medicine.disease, MESH: Quantitative Trait Loci, Human genetics, Psychologie, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, Expression quantitative trait loci, MESH: Multifactorial Inheritance, Quantitative Trait Loci/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: International audience; Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
Published: 2021

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