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1. Fine-mapping genomic loci refines bipolar disorder risk genes

Author: Koromina, Maria, Ravi, Ashvin, Panagiotaropoulou, Georgia, Schilder, Brian M., Humphrey, Jack, Braun, Alice, Bidgeli, Tim, Chatzinakos, Chris, Coombes, Brandon, Kim, Jaeyoung, Liu, Xiaoxi, Terao, Chikashi, O'Connell, Kevin S., Adams, Mark, Adolfsson, Rolf, Alda, Martin, Alfredsson, Lars, Andlauer, Till, Andreassen, Ole A., Antoniou, Anastasia, Baune, Bernhard T., Bengesser, Susanne, Biernacka, Joanna, Boehnke, Michael, Bosch, Rosa, Cairns, Murray, Carr, Vaughan J., Casas Brugué, Miquel, Catts, Stanley, Cichon, Sven, Corvin, Aiden, Craddock, Nicholas, Dafnas, Konstantinos, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Di Florio, Arianna, Dikeos, Dimitris, Fellendorf, Frederike Tabea, Ferentinos, Panagiotis, Forstner, Andreas Josef, Forty, Liz, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gizer, Ian R., Gordon-Smith, Katherine, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Guzman-Parra, José, Hahn, Tim, Henskens, Frans, Hillert, Jan, Jablensky, Assen V., Jones, Lisa, Jones, Ian, Jonsson, Lina, Kelsoe, John R., Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Kogevinas, Manolis, Landén, Mikael, Leboyer, Marion, Lenger, Melanie, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, MacIntyre, Donald, Martin, Nicholas G., Maratou, Eirini, Mathews, Carol A., Mayoral, Fermı́n, McElroy, Susan L., McGregor, Nathaniel W., McIntosh, Andrew M., McQuillin, Andrew, Michie, Patricia, Milanova, Vihra, Mitchell, Philip B., Moutsatsou, Paraskevi, Mowry, Bryan, Müller-Myhsok, Bertram, Myers, Richard M., Nenadić, Igor, Nöthen, Markus Maria, O'Donovan, Claire, O'Donovan, Michael, Ophoff, Roel André, Owen, Michael J., Pantelis, Christos, Pato, Carlos, Pato, Michele T., Patrinos, George P., Pawlak, Joanna M., Perlis, Roy H., Porichi, Evgenia, Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rietschel, Marcella, Schall, Ulrich, Schulze, Thomas Gerd, Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Shannon Weickert, Cynthia, Smoller, Jordan W., Soler Artigas, Marı́a, Stein, Dan J., Streit, Fabian, Toma, Claudio, Tooney, Paul, Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas, Witt, Stephanie H., Hong, Kyung Sue, Ikeda, Masashi, Iwata, Nakao, Świątkowska, Beata, Won, Hong-Hee, Edenberg, Howard J., Ripke, Stephan, Raj, Towfique, Coleman, Jonathan R. I., Mullins, Niamh, Koromina, Maria, Ravi, Ashvin, Panagiotaropoulou, Georgia, Schilder, Brian M., Humphrey, Jack, Braun, Alice, Bidgeli, Tim, Chatzinakos, Chris, Coombes, Brandon, Kim, Jaeyoung, Liu, Xiaoxi, Terao, Chikashi, O'Connell, Kevin S., Adams, Mark, Adolfsson, Rolf, Alda, Martin, Alfredsson, Lars, Andlauer, Till, Andreassen, Ole A., Antoniou, Anastasia, Baune, Bernhard T., Bengesser, Susanne, Biernacka, Joanna, Boehnke, Michael, Bosch, Rosa, Cairns, Murray, Carr, Vaughan J., Casas Brugué, Miquel, Catts, Stanley, Cichon, Sven, Corvin, Aiden, Craddock, Nicholas, Dafnas, Konstantinos, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Di Florio, Arianna, Dikeos, Dimitris, Fellendorf, Frederike Tabea, Ferentinos, Panagiotis, Forstner, Andreas Josef, Forty, Liz, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gizer, Ian R., Gordon-Smith, Katherine, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Guzman-Parra, José, Hahn, Tim, Henskens, Frans, Hillert, Jan, Jablensky, Assen V., Jones, Lisa, Jones, Ian, Jonsson, Lina, Kelsoe, John R., Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Kogevinas, Manolis, Landén, Mikael, Leboyer, Marion, Lenger, Melanie, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, MacIntyre, Donald, Martin, Nicholas G., Maratou, Eirini, Mathews, Carol A., Mayoral, Fermı́n, McElroy, Susan L., McGregor, Nathaniel W., McIntosh, Andrew M., McQuillin, Andrew, Michie, Patricia, Milanova, Vihra, Mitchell, Philip B., Moutsatsou, Paraskevi, Mowry, Bryan, Müller-Myhsok, Bertram, Myers, Richard M., Nenadić, Igor, Nöthen, Markus Maria, O'Donovan, Claire, O'Donovan, Michael, Ophoff, Roel André, Owen, Michael J., Pantelis, Christos, Pato, Carlos, Pato, Michele T., Patrinos, George P., Pawlak, Joanna M., Perlis, Roy H., Porichi, Evgenia, Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rietschel, Marcella, Schall, Ulrich, Schulze, Thomas Gerd, Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Shannon Weickert, Cynthia, Smoller, Jordan W., Soler Artigas, Marı́a, Stein, Dan J., Streit, Fabian, Toma, Claudio, Tooney, Paul, Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas, Witt, Stephanie H., Hong, Kyung Sue, Ikeda, Masashi, Iwata, Nakao, Świątkowska, Beata, Won, Hong-Hee, Edenberg, Howard J., Ripke, Stephan, Raj, Towfique, Coleman, Jonathan R. I., and Mullins, Niamh
Abstract: Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
Published: 2024

2. Using Polygenic Hazard Scores to Predict Age at Onset of Alzheimer's Disease in Nordic Populations

Author: Motazedi, Ehsan, Cheng, Weiqiu, Thomassen, Jesper Q., Frei, Oleksandr, Rongve, Arvid, Athanasiu, Lavinia, Bahrami, Shahram, Shadrin, Alexey, Ulstein, Ingun, Stordal, Eystein, Brækhus, Anne, Saltvedt, Ingvild, Sando, Sigrid B., O'Connell, Kevin S., Hindley, Guy, Van Der Meer, Dennis, Bergh, Sverre, Nordestgaard, Brge G., Tybjærg-Hansen, Anne, Brthen, Geir, Pihlstrm, Lasse, Djurovic, Srdjan, Frikke-Schmidt, Ruth, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Seibert, Tyler M., Dale, Anders M., Fan, Chun C., Andreassen, Ole A., Motazedi, Ehsan, Cheng, Weiqiu, Thomassen, Jesper Q., Frei, Oleksandr, Rongve, Arvid, Athanasiu, Lavinia, Bahrami, Shahram, Shadrin, Alexey, Ulstein, Ingun, Stordal, Eystein, Brækhus, Anne, Saltvedt, Ingvild, Sando, Sigrid B., O'Connell, Kevin S., Hindley, Guy, Van Der Meer, Dennis, Bergh, Sverre, Nordestgaard, Brge G., Tybjærg-Hansen, Anne, Brthen, Geir, Pihlstrm, Lasse, Djurovic, Srdjan, Frikke-Schmidt, Ruth, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Seibert, Tyler M., Dale, Anders M., Fan, Chun C., and Andreassen, Ole A.
Abstract: Background: Polygenic hazard scores (PHS) estimate age-dependent genetic risk of late-onset Alzheimer's disease (AD), but there is limited information about the performance of PHS on real-world data where the population of interest differs from the model development population and part of the model genotypes are missing or need to be imputed. Objective: The aim of this study was to estimate age-dependent risk of late-onset AD using polygenic predictors in Nordic populations. Methods: We used Desikan PHS model, based on Cox proportional hazards assumption, to obtain age-dependent hazard scores for AD from individual genotypes in the Norwegian DemGene cohort (n = 2,772). We assessed the risk discrimination and calibration of Desikan model and extended it by adding new genotype markers (the Desikan Nordic model). Finally, we evaluated both Desikan and Desikan Nordic models in two independent Danish cohorts: The Copenhagen City Heart Study (CCHS) cohort (n = 7,643) and The Copenhagen General Population Study (CGPS) cohort (n = 10,886). Results: We showed a robust prediction efficiency of Desikan model in stratifying AD risk groups in Nordic populations, even when some of the model SNPs were missing or imputed. We attempted to improve Desikan PHS model by adding new SNPs to it, but we still achieved similar risk discrimination and calibration with the extended model. Conclusion: PHS modeling has the potential to guide the timing of treatment initiation based on individual risk profiles and can help enrich clinical trials with people at high risk to AD in Nordic populations.
Published: 2022

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

Author: Mullins, Niamh, Mullins, Niamh, Forstner, Andreas J, O'Connell, Kevin S, Coombes, Brandon, Coleman, Jonathan RI, Qiao, Zhen, Als, Thomas D, Bigdeli, Tim B, Børte, Sigrid, Bryois, Julien, 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, Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S, Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C, Bergen, Sarah E, Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P, Bosch, Rosa, Brum, Murielle, Brumpton, Ben M, Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M, Dale, Anders M, Dalkner, Nina, David, Friederike S, Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L, Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I Nicol, Fiorentino, Alessia, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R, Gordon, Scott D, Gordon-Smith, Katherine, Greenwood, Tiffany A, Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, Kalman, Janos L, Mullins, Niamh, Mullins, Niamh, Forstner, Andreas J, O'Connell, Kevin S, Coombes, Brandon, Coleman, Jonathan RI, Qiao, Zhen, Als, Thomas D, Bigdeli, Tim B, Børte, Sigrid, Bryois, Julien, 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, Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S, Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C, Bergen, Sarah E, Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P, Bosch, Rosa, Brum, Murielle, Brumpton, Ben M, Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M, Dale, Anders M, Dalkner, Nina, David, Friederike S, Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L, Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I Nicol, Fiorentino, Alessia, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R, Gordon, Scott D, Gordon-Smith, Katherine, Greenwood, Tiffany A, Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Kalman, Janos L
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.
Published: 2021

4. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., Medland, Sarah E., Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., and Medland, Sarah E.
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10−8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
Published: 2021
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5. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., Medland, Sarah E., Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., and Medland, Sarah E.
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10−8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
Published: 2021

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

Author: Mullins, Niamh, Forstner, Andreas J., O'Connell, Kevin S., Coombes, Brandon, Coleman, Jonathan R., I, Qiao, Zhen, Als, Thomas D., Bigdeli, Tim B., Borte, Sigrid, Bryois, Julien, 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., Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Baekvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Pedersen, Carsten Bocker, Boen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsashagen, Torbjorn, Escott-Price, Valentina, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B., Frisen, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Pedersen, Marianne Giortz, Gizer, Ian R., Gordon, Scott D., Gordon-Smith, Katherine, Greenwood, Tiffany A., Grove, Jakob, Guzman-Parra, Jose, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A., Huckins, Laura, Jamain, Stephane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., 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, Lucae, Susanne, Lundberg, Martin, MacIntyre, Donald J., Maier, Wolfgang, Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, Mattheisen, Manuel, McCarroll, Steven A., McGregor, Nathaniel W., McGuffin, Peter, McKay, James D., Medeiros, Helena, Medland, Sarah E., Millischer, Vincent, Montgomery, Grant W., Moran, Jennifer L., Morris, Derek W., Muhleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Loohuis, Loes M. Olde, Oruc, Lilijana, Papiol, Sergi, Pardinas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Potash, James B., Quested, Digby, Raj, Towfique, Rapaport, Mark H., DePaulo, J. Raymond, Regeer, Eline J., Rice, John P., Rivas, Fabio, Rivera, Margarita, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sanchez-Mora, Cristina, Schulte, Eva C., Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sigurdsson, Engilbert, Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Hansen, Christine Soholm, Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Swiatkowska, Beata, Terao, Chikashi, Thorgeirsson, Thorgeir E., Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Witt, Stephanie H., Xi, Simon, Xu, Wei, Yang, Jessica Mei Kay, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Borglum, Anders D., Breen, Gerome, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dannlowski, Udo, Dikeos, Dimitris, Esko, Tonu, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Goes, Fernando, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hougaard, David M., Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen, V, Jones, Ian, Jones, Lisa A., Kahn, Rene S., Kelsoe, John R., Kirov, George, Landen, Mikael, Leboyer, Marion, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Martin, Nicholas G., Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Milani, Lili, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Mowry, Bryan, Muller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Nordentoft, Merete, Nothen, Markus M., ODonovan, Michael C., Oedegaard, Ketil J., Olsson, Tomas, Owen, Michael J., Paciga, Sara A., Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Perlis, Roy H., Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribases, Marta, Rietschel, Marcella, Ripke, Stephan, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Streit, Fabian, Sullivan, Patrick F., Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Werge, Thomas, Wray, Naomi R., Zwart, JohnAnker, Biernacka, Joanna M., Nurnberger, John, I, Cichon, Sven, Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Mullins, Niamh, Forstner, Andreas J., O'Connell, Kevin S., Coombes, Brandon, Coleman, Jonathan R., I, Qiao, Zhen, Als, Thomas D., Bigdeli, Tim B., Borte, Sigrid, Bryois, Julien, 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., Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Baekvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Pedersen, Carsten Bocker, Boen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsashagen, Torbjorn, Escott-Price, Valentina, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B., Frisen, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Pedersen, Marianne Giortz, Gizer, Ian R., Gordon, Scott D., Gordon-Smith, Katherine, Greenwood, Tiffany A., Grove, Jakob, Guzman-Parra, Jose, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A., Huckins, Laura, Jamain, Stephane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., 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, Lucae, Susanne, Lundberg, Martin, MacIntyre, Donald J., Maier, Wolfgang, Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, Mattheisen, Manuel, McCarroll, Steven A., McGregor, Nathaniel W., McGuffin, Peter, McKay, James D., Medeiros, Helena, Medland, Sarah E., Millischer, Vincent, Montgomery, Grant W., Moran, Jennifer L., Morris, Derek W., Muhleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Loohuis, Loes M. Olde, Oruc, Lilijana, Papiol, Sergi, Pardinas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Potash, James B., Quested, Digby, Raj, Towfique, Rapaport, Mark H., DePaulo, J. Raymond, Regeer, Eline J., Rice, John P., Rivas, Fabio, Rivera, Margarita, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sanchez-Mora, Cristina, Schulte, Eva C., Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sigurdsson, Engilbert, Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Hansen, Christine Soholm, Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Swiatkowska, Beata, Terao, Chikashi, Thorgeirsson, Thorgeir E., Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Witt, Stephanie H., Xi, Simon, Xu, Wei, Yang, Jessica Mei Kay, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Borglum, Anders D., Breen, Gerome, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dannlowski, Udo, Dikeos, Dimitris, Esko, Tonu, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Goes, Fernando, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hougaard, David M., Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen, V, Jones, Ian, Jones, Lisa A., Kahn, Rene S., Kelsoe, John R., Kirov, George, Landen, Mikael, Leboyer, Marion, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Martin, Nicholas G., Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Milani, Lili, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Mowry, Bryan, Muller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Nordentoft, Merete, Nothen, Markus M., ODonovan, Michael C., Oedegaard, Ketil J., Olsson, Tomas, Owen, Michael J., Paciga, Sara A., Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Perlis, Roy H., Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribases, Marta, Rietschel, Marcella, Ripke, Stephan, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Streit, Fabian, Sullivan, Patrick F., Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Werge, Thomas, Wray, Naomi R., Zwart, JohnAnker, Biernacka, Joanna M., Nurnberger, John, I, Cichon, Sven, Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., and Andreassen, Ole A.
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. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
Published: 2021

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

Author: Mullins, Niamh, Mullins, Niamh, Forstner, Andreas J, O'Connell, Kevin S, Coombes, Brandon, Coleman, Jonathan RI, Qiao, Zhen, Als, Thomas D, Bigdeli, Tim B, Børte, Sigrid, Bryois, Julien, 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, Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S, Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C, Bergen, Sarah E, Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P, Bosch, Rosa, Brum, Murielle, Brumpton, Ben M, Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M, Dale, Anders M, Dalkner, Nina, David, Friederike S, Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L, Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I Nicol, Fiorentino, Alessia, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R, Gordon, Scott D, Gordon-Smith, Katherine, Greenwood, Tiffany A, Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, Kalman, Janos L, Mullins, Niamh, Mullins, Niamh, Forstner, Andreas J, O'Connell, Kevin S, Coombes, Brandon, Coleman, Jonathan RI, Qiao, Zhen, Als, Thomas D, Bigdeli, Tim B, Børte, Sigrid, Bryois, Julien, 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, Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S, Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C, Bergen, Sarah E, Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P, Bosch, Rosa, Brum, Murielle, Brumpton, Ben M, Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M, Dale, Anders M, Dalkner, Nina, David, Friederike S, Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L, Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I Nicol, Fiorentino, Alessia, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R, Gordon, Scott D, Gordon-Smith, Katherine, Greenwood, Tiffany A, Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Kalman, Janos L
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.
Published: 2021

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

Author: Mullins, Niamh, Forstner, Andreas J., O’Connell, Kevin S., Coombes, Brandon, Coleman, Jonathan R. I., Qiao, Zhen, Als, Thomas D., Bigdeli, Tim B., Børte, Sigrid, Bryois, Julien, 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., Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R., Gordon, Scott D., Gordon-Smith, Katherine, Greenwood, Tiffany A., Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., 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, Lucae, Susanne, Lundberg, Martin, MacIntyre, Donald J., Magnusson, Sigurdur H., Maier, Wolfgang, Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, Mattheisen, Manuel, McCarroll, Steven A., McGregor, Nathaniel W., McGuffin, Peter, McKay, James D., Medeiros, Helena, Medland, Sarah E., Millischer, Vincent, Montgomery, Grant W., 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, Potash, James B., Quested, Digby, Raj, Towfique, Rapaport, Mark H., DePaulo, J. Raymond, Regeer, Eline J., Rice, John P., Rivas, Fabio, Rivera, Margarita, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Schulte, Eva C., Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sigurdsson, Engilbert, Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Smith, Daniel J., Sobell, Janet L., Søholm Hansen, Christine, Soler Artigas, Maria, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Thorgeirsson, Thorgeir E., Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Witt, Stephanie H., Xi, Simon, Xu, Wei, Yang, Jessica Mei Kay, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Børglum, Anders D., Breen, Gerome, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dannlowski, Udo, Dikeos, Dimitris, Esko, Tõnu, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Goes, Fernando S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hougaard, David M., Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Jones, Ian, Jones, Lisa A., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Martin, Nicholas G., Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Milani, Lili, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Mowry, Bryan, Müller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Nordentoft, Merete, Nöthen, Markus M., O’Donovan, Michael C., Oedegaard, Ketil J., Olsson, Tomas, Owen, Michael J., Paciga, Sara A., Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Perlis, Roy H., Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rietschel, Marcella, Ripke, Stephan, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Shannon Weickert, Cynthia, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Streit, Fabian, Sullivan, Patrick F., Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Werge, Thomas, Wray, Naomi R., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Cichon, Sven, Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Mullins, Niamh, Forstner, Andreas J., O’Connell, Kevin S., Coombes, Brandon, Coleman, Jonathan R. I., Qiao, Zhen, Als, Thomas D., Bigdeli, Tim B., Børte, Sigrid, Bryois, Julien, 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., Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R., Gordon, Scott D., Gordon-Smith, Katherine, Greenwood, Tiffany A., Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., 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, Lucae, Susanne, Lundberg, Martin, MacIntyre, Donald J., Magnusson, Sigurdur H., Maier, Wolfgang, Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, Mattheisen, Manuel, McCarroll, Steven A., McGregor, Nathaniel W., McGuffin, Peter, McKay, James D., Medeiros, Helena, Medland, Sarah E., Millischer, Vincent, Montgomery, Grant W., 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, Potash, James B., Quested, Digby, Raj, Towfique, Rapaport, Mark H., DePaulo, J. Raymond, Regeer, Eline J., Rice, John P., Rivas, Fabio, Rivera, Margarita, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Schulte, Eva C., Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sigurdsson, Engilbert, Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Smith, Daniel J., Sobell, Janet L., Søholm Hansen, Christine, Soler Artigas, Maria, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Thorgeirsson, Thorgeir E., Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Witt, Stephanie H., Xi, Simon, Xu, Wei, Yang, Jessica Mei Kay, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Børglum, Anders D., Breen, Gerome, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dannlowski, Udo, Dikeos, Dimitris, Esko, Tõnu, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Goes, Fernando S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hougaard, David M., Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Jones, Ian, Jones, Lisa A., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Martin, Nicholas G., Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Milani, Lili, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Mowry, Bryan, Müller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Nordentoft, Merete, Nöthen, Markus M., O’Donovan, Michael C., Oedegaard, Ketil J., Olsson, Tomas, Owen, Michael J., Paciga, Sara A., Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Perlis, Roy H., Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rietschel, Marcella, Ripke, Stephan, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Shannon Weickert, Cynthia, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Streit, Fabian, Sullivan, Patrick F., Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Werge, Thomas, Wray, Naomi R., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Cichon, Sven, Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., and Andreassen, Ole A.
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.
Published: 2021
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9. Genome-wide Association Analysis of Parkinson's Disease and Schizophrenia Reveals Shared Genetic Architecture and Identifies Novel Risk Loci.

Author: Smeland, Olav B, Smeland, Olav B, Shadrin, Alexey, Bahrami, Shahram, Broce, Iris, Tesli, Martin, Frei, Oleksandr, Wirgenes, Katrine V, O'Connell, Kevin S, Krull, Florian, Bettella, Francesco, Steen, Nils Eiel, Sugrue, Leo, Wang, Yunpeng, Svenningsson, Per, Sharma, Manu, Pihlstrøm, Lasse, Toft, Mathias, O'Donovan, Michael, Djurovic, Srdjan, Desikan, Rahul, Dale, Anders M, Andreassen, Ole A, Smeland, Olav B, Smeland, Olav B, Shadrin, Alexey, Bahrami, Shahram, Broce, Iris, Tesli, Martin, Frei, Oleksandr, Wirgenes, Katrine V, O'Connell, Kevin S, Krull, Florian, Bettella, Francesco, Steen, Nils Eiel, Sugrue, Leo, Wang, Yunpeng, Svenningsson, Per, Sharma, Manu, Pihlstrøm, Lasse, Toft, Mathias, O'Donovan, Michael, Djurovic, Srdjan, Desikan, Rahul, Dale, Anders M, and Andreassen, Ole A
Abstract: BackgroundParkinson's disease (PD) and schizophrenia (SCZ) are heritable brain disorders that involve dysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between the disorders, and movement disturbances are common in patients with SCZ before treatment with antipsychotic drugs. Despite this, little is known about shared genetic etiology between the disorders.MethodsWe analyzed recent large genome-wide association studies on patients with SCZ (N = 77,096) and PD (N = 417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants and improve statistical power for genetic discovery. Using a variety of biological resources, we functionally characterized the identified genomic loci.ResultsWe observed genetic enrichment in PD conditional on associations with SCZ and vice versa, indicating polygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified 9 novel PD risk loci and 1 novel SCZ locus at conditional FDR < .01. Furthermore, we identified 9 genomic loci jointly associated with PD and SCZ at conjunctional FDR < .05. There was an even distribution of antagonistic and agonistic effect directions among the shared loci, in line with the insignificant genetic correlation between the disorders. Of 67 genes mapped to the shared loci, 65 are expressed in the human brain and show cell type-specific expression profiles.ConclusionsAltogether, the study increases understanding of the genetic architectures underlying SCZ and PD, indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinical features between the disorders.
Published: 2021

10. Genome-wide association study identifies 48 common genetic variants associated with handedness.

Author: Cuellar-Partida, Gabriel, Cuellar-Partida, Gabriel, Tung, Joyce Y, Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A, Barroso, Inês, Beckmann, Jacques S, Boks, Marco P, Boomsma, Dorret I, Boyd, Heather A, Breteler, Monique MB, Campbell, Harry, Chasman, Daniel I, Cherkas, Lynn F, Davies, Gail, de Geus, Eco JC, Deary, Ian J, Deloukas, Panos, Dick, Danielle M, Duffy, David L, Eriksson, Johan G, Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D, Han, Jiali, Hansen, Thomas F, Hartmann, Annette M, Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A, Hirschhorn, Joel N, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Liang-Dar, Ikram, M Arfan, Kaprio, Jaakko, Kemp, John P, Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth JF, Luciano, Michelle, Magnusson, Sigurdur H, Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G, McArdle, Wendy L, McCarthy, Mark I, Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A, Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R, O'Connell, Kevin S, Ophoff, Roel A, Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda WJH, Polasek, Ozren, Pramstaller, Peter P, Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H, Smith, George Davey, Smoller, Jordan W, Soranzo, Nicole, Spector, Tim D, Pourcain, Beate St, Starr, John M, Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J, Uitterlinden, André G, van Duijn, Cornelia M, van Rooij, Frank JA, Vink, Jaqueline M, Vollenweider, Peter, Vuoksimaa, Eero, Cuellar-Partida, Gabriel, Cuellar-Partida, Gabriel, Tung, Joyce Y, Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A, Barroso, Inês, Beckmann, Jacques S, Boks, Marco P, Boomsma, Dorret I, Boyd, Heather A, Breteler, Monique MB, Campbell, Harry, Chasman, Daniel I, Cherkas, Lynn F, Davies, Gail, de Geus, Eco JC, Deary, Ian J, Deloukas, Panos, Dick, Danielle M, Duffy, David L, Eriksson, Johan G, Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D, Han, Jiali, Hansen, Thomas F, Hartmann, Annette M, Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A, Hirschhorn, Joel N, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Liang-Dar, Ikram, M Arfan, Kaprio, Jaakko, Kemp, John P, Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth JF, Luciano, Michelle, Magnusson, Sigurdur H, Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G, McArdle, Wendy L, McCarthy, Mark I, Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A, Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R, O'Connell, Kevin S, Ophoff, Roel A, Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda WJH, Polasek, Ozren, Pramstaller, Peter P, Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H, Smith, George Davey, Smoller, Jordan W, Soranzo, Nicole, Spector, Tim D, Pourcain, Beate St, Starr, John M, Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J, Uitterlinden, André G, van Duijn, Cornelia M, van Rooij, Frank JA, Vink, Jaqueline M, Vollenweider, Peter, and Vuoksimaa, Eero
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
Published: 2021

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

Author: Mullins, Niamh, Forstner, Andreas J., O'Connell, Kevin S., Coombes, Brandon, Coleman, Jonathan R., I, Qiao, Zhen, Als, Thomas D., Bigdeli, Tim B., Borte, Sigrid, Bryois, Julien, 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., Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Baekvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Pedersen, Carsten Bocker, Boen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsashagen, Torbjorn, Escott-Price, Valentina, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B., Frisen, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Pedersen, Marianne Giortz, Gizer, Ian R., Gordon, Scott D., Gordon-Smith, Katherine, Greenwood, Tiffany A., Grove, Jakob, Guzman-Parra, Jose, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A., Huckins, Laura, Jamain, Stephane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., 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, Lucae, Susanne, Lundberg, Martin, MacIntyre, Donald J., Maier, Wolfgang, Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, Mattheisen, Manuel, McCarroll, Steven A., McGregor, Nathaniel W., McGuffin, Peter, McKay, James D., Medeiros, Helena, Medland, Sarah E., Millischer, Vincent, Montgomery, Grant W., Moran, Jennifer L., Morris, Derek W., Muhleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Loohuis, Loes M. Olde, Oruc, Lilijana, Papiol, Sergi, Pardinas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Potash, James B., Quested, Digby, Raj, Towfique, Rapaport, Mark H., DePaulo, J. Raymond, Regeer, Eline J., Rice, John P., Rivas, Fabio, Rivera, Margarita, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sanchez-Mora, Cristina, Schulte, Eva C., Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sigurdsson, Engilbert, Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Hansen, Christine Soholm, Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Swiatkowska, Beata, Terao, Chikashi, Thorgeirsson, Thorgeir E., Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Witt, Stephanie H., Xi, Simon, Xu, Wei, Yang, Jessica Mei Kay, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Borglum, Anders D., Breen, Gerome, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dannlowski, Udo, Dikeos, Dimitris, Esko, Tonu, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Goes, Fernando, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hougaard, David M., Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen, V, Jones, Ian, Jones, Lisa A., Kahn, Rene S., Kelsoe, John R., Kirov, George, Landen, Mikael, Leboyer, Marion, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Martin, Nicholas G., Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Milani, Lili, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Mowry, Bryan, Muller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Nordentoft, Merete, Nothen, Markus M., ODonovan, Michael C., Oedegaard, Ketil J., Olsson, Tomas, Owen, Michael J., Paciga, Sara A., Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Perlis, Roy H., Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribases, Marta, Rietschel, Marcella, Ripke, Stephan, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Streit, Fabian, Sullivan, Patrick F., Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Werge, Thomas, Wray, Naomi R., Zwart, JohnAnker, Biernacka, Joanna M., Nurnberger, John, I, Cichon, Sven, Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Mullins, Niamh, Forstner, Andreas J., O'Connell, Kevin S., Coombes, Brandon, Coleman, Jonathan R., I, Qiao, Zhen, Als, Thomas D., Bigdeli, Tim B., Borte, Sigrid, Bryois, Julien, 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., Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Baekvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Pedersen, Carsten Bocker, Boen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsashagen, Torbjorn, Escott-Price, Valentina, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B., Frisen, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Pedersen, Marianne Giortz, Gizer, Ian R., Gordon, Scott D., Gordon-Smith, Katherine, Greenwood, Tiffany A., Grove, Jakob, Guzman-Parra, Jose, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A., Huckins, Laura, Jamain, Stephane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., 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, Lucae, Susanne, Lundberg, Martin, MacIntyre, Donald J., Maier, Wolfgang, Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, Mattheisen, Manuel, McCarroll, Steven A., McGregor, Nathaniel W., McGuffin, Peter, McKay, James D., Medeiros, Helena, Medland, Sarah E., Millischer, Vincent, Montgomery, Grant W., Moran, Jennifer L., Morris, Derek W., Muhleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Loohuis, Loes M. Olde, Oruc, Lilijana, Papiol, Sergi, Pardinas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Potash, James B., Quested, Digby, Raj, Towfique, Rapaport, Mark H., DePaulo, J. Raymond, Regeer, Eline J., Rice, John P., Rivas, Fabio, Rivera, Margarita, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sanchez-Mora, Cristina, Schulte, Eva C., Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sigurdsson, Engilbert, Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Hansen, Christine Soholm, Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Swiatkowska, Beata, Terao, Chikashi, Thorgeirsson, Thorgeir E., Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Witt, Stephanie H., Xi, Simon, Xu, Wei, Yang, Jessica Mei Kay, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Borglum, Anders D., Breen, Gerome, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dannlowski, Udo, Dikeos, Dimitris, Esko, Tonu, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Goes, Fernando, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hougaard, David M., Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen, V, Jones, Ian, Jones, Lisa A., Kahn, Rene S., Kelsoe, John R., Kirov, George, Landen, Mikael, Leboyer, Marion, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Martin, Nicholas G., Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Milani, Lili, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Mowry, Bryan, Muller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Nordentoft, Merete, Nothen, Markus M., ODonovan, Michael C., Oedegaard, Ketil J., Olsson, Tomas, Owen, Michael J., Paciga, Sara A., Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Perlis, Roy H., Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribases, Marta, Rietschel, Marcella, Ripke, Stephan, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Streit, Fabian, Sullivan, Patrick F., Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Werge, Thomas, Wray, Naomi R., Zwart, JohnAnker, Biernacka, Joanna M., Nurnberger, John, I, Cichon, Sven, Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., and Andreassen, Ole A.
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. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
Published: 2021

12. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Ines, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M. B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J. C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tonu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkila, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke-Jan, Huffman, Jennifer E., Hwang, Liang-Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J. F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O'Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W. J. H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefansson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefansson, Kari, Timpson, Nicholas J., Uitterlinden, Andre G., van Duijn, Cornelia M., van Rooij, Frank J. A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gerard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. -Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Magi, Reedik, Neale, Benjamin M., Evans, David M., Medland, Sarah E., Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Ines, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M. B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J. C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tonu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkila, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke-Jan, Huffman, Jennifer E., Hwang, Liang-Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J. F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O'Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W. J. H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefansson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefansson, Kari, Timpson, Nicholas J., Uitterlinden, Andre G., van Duijn, Cornelia M., van Rooij, Frank J. A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gerard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. -Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Magi, Reedik, Neale, Benjamin M., Evans, David M., and Medland, Sarah E.
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P <5 x 10(-8)) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r(G) = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.
Published: 2021

13. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., Medland, Sarah E., Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., and Medland, Sarah E.
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10−8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
Published: 2021
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14. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Ines, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M. B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J. C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tonu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkila, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke-Jan, Huffman, Jennifer E., Hwang, Liang-Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J. F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O'Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W. J. H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefansson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefansson, Kari, Timpson, Nicholas J., Uitterlinden, Andre G., van Duijn, Cornelia M., van Rooij, Frank J. A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gerard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. -Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Magi, Reedik, Neale, Benjamin M., Evans, David M., Medland, Sarah E., Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Ines, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M. B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J. C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tonu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkila, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke-Jan, Huffman, Jennifer E., Hwang, Liang-Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J. F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O'Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W. J. H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefansson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefansson, Kari, Timpson, Nicholas J., Uitterlinden, Andre G., van Duijn, Cornelia M., van Rooij, Frank J. A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gerard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. -Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Magi, Reedik, Neale, Benjamin M., Evans, David M., and Medland, Sarah E.
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P <5 x 10(-8)) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r(G) = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.
Published: 2021

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

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
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16. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
Full Text: View/download PDF

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

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
Full Text: View/download PDF

18. Quantifying the Polygenic Architecture of the Human Cerebral Cortex: Extensive Genetic Overlap between Cortical Thickness and Surface Area.

Author: van der Meer, Dennis, van der Meer, Dennis, Frei, Oleksandr, Kaufmann, Tobias, Chen, Chi-Hua, Thompson, Wesley K, O'Connell, Kevin S, Monereo Sánchez, Jennifer, Linden, David EJ, Westlye, Lars T, Dale, Anders M, Andreassen, Ole A, van der Meer, Dennis, van der Meer, Dennis, Frei, Oleksandr, Kaufmann, Tobias, Chen, Chi-Hua, Thompson, Wesley K, O'Connell, Kevin S, Monereo Sánchez, Jennifer, Linden, David EJ, Westlye, Lars T, Dale, Anders M, and Andreassen, Ole A
Abstract: The thickness of the cerebral cortical sheet and its surface area are highly heritable traits thought to have largely distinct polygenic architectures. Despite large-scale efforts, the majority of their genetic determinants remain unknown. Our ability to identify causal genetic variants can be improved by employing brain measures that better map onto the biology we seek to understand. Such measures may have fewer variants but with larger effects, that is, lower polygenicity and higher discoverability. Using Gaussian mixture modeling, we estimated the number of causal variants shared between mean cortical thickness and total surface area, as well as the polygenicity and discoverability of regional measures. We made use of UK Biobank data from 30 880 healthy White European individuals (mean age 64.3, standard deviation 7.5, 52.1% female). We found large genetic overlap between total surface area and mean thickness, sharing 4016 out of 7941 causal variants. Regional surface area was more discoverable (P = 2.6 × 10-6) and less polygenic (P = 0.004) than regional thickness measures. These findings may serve as a roadmap for improved future GWAS studies; knowledge of which measures are most discoverable may be used to boost identification of genetic predictors and thereby gain a better understanding of brain morphology.
Published: 2020

19. Quantifying the Polygenic Architecture of the Human Cerebral Cortex: Extensive Genetic Overlap between Cortical Thickness and Surface Area.

Author: van der Meer, Dennis, van der Meer, Dennis, Frei, Oleksandr, Kaufmann, Tobias, Chen, Chi-Hua, Thompson, Wesley K, O'Connell, Kevin S, Monereo Sánchez, Jennifer, Linden, David EJ, Westlye, Lars T, Dale, Anders M, Andreassen, Ole A, van der Meer, Dennis, van der Meer, Dennis, Frei, Oleksandr, Kaufmann, Tobias, Chen, Chi-Hua, Thompson, Wesley K, O'Connell, Kevin S, Monereo Sánchez, Jennifer, Linden, David EJ, Westlye, Lars T, Dale, Anders M, and Andreassen, Ole A
Abstract: The thickness of the cerebral cortical sheet and its surface area are highly heritable traits thought to have largely distinct polygenic architectures. Despite large-scale efforts, the majority of their genetic determinants remain unknown. Our ability to identify causal genetic variants can be improved by employing brain measures that better map onto the biology we seek to understand. Such measures may have fewer variants but with larger effects, that is, lower polygenicity and higher discoverability. Using Gaussian mixture modeling, we estimated the number of causal variants shared between mean cortical thickness and total surface area, as well as the polygenicity and discoverability of regional measures. We made use of UK Biobank data from 30 880 healthy White European individuals (mean age 64.3, standard deviation 7.5, 52.1% female). We found large genetic overlap between total surface area and mean thickness, sharing 4016 out of 7941 causal variants. Regional surface area was more discoverable (P = 2.6 × 10-6) and less polygenic (P = 0.004) than regional thickness measures. These findings may serve as a roadmap for improved future GWAS studies; knowledge of which measures are most discoverable may be used to boost identification of genetic predictors and thereby gain a better understanding of brain morphology.
Published: 2020

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

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
Full Text: View/download PDF

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

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
Full Text: View/download PDF

22. Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation.

Author: Frei, Oleksandr, Frei, Oleksandr, Holland, Dominic, Smeland, Olav B, Shadrin, Alexey A, Fan, Chun Chieh, Maeland, Steffen, O'Connell, Kevin S, Wang, Yunpeng, Djurovic, Srdjan, Thompson, Wesley K, Andreassen, Ole A, Dale, Anders M, Frei, Oleksandr, Frei, Oleksandr, Holland, Dominic, Smeland, Olav B, Shadrin, Alexey A, Fan, Chun Chieh, Maeland, Steffen, O'Connell, Kevin S, Wang, Yunpeng, Djurovic, Srdjan, Thompson, Wesley K, Andreassen, Ole A, and Dale, Anders M
Abstract: Accumulating evidence from genome wide association studies (GWAS) suggests an abundance of shared genetic influences among complex human traits and disorders, such as mental disorders. Here we introduce a statistical tool, MiXeR, which quantifies polygenic overlap irrespective of genetic correlation, using GWAS summary statistics. MiXeR results are presented as a Venn diagram of unique and shared polygenic components across traits. At 90% of SNP-heritability explained for each phenotype, MiXeR estimates that 8.3 K variants causally influence schizophrenia and 6.4 K influence bipolar disorder. Among these variants, 6.2 K are shared between the disorders, which have a high genetic correlation. Further, MiXeR uncovers polygenic overlap between schizophrenia and educational attainment. Despite a genetic correlation close to zero, the phenotypes share 8.3 K causal variants, while 2.5 K additional variants influence only educational attainment. By considering the polygenicity, discoverability and heritability of complex phenotypes, MiXeR analysis may improve our understanding of cross-trait genetic architectures.
Published: 2019

23. Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation.

Author: Frei, Oleksandr, Frei, Oleksandr, Holland, Dominic, Smeland, Olav B, Shadrin, Alexey A, Fan, Chun Chieh, Maeland, Steffen, O'Connell, Kevin S, Wang, Yunpeng, Djurovic, Srdjan, Thompson, Wesley K, Andreassen, Ole A, Dale, Anders M, Frei, Oleksandr, Frei, Oleksandr, Holland, Dominic, Smeland, Olav B, Shadrin, Alexey A, Fan, Chun Chieh, Maeland, Steffen, O'Connell, Kevin S, Wang, Yunpeng, Djurovic, Srdjan, Thompson, Wesley K, Andreassen, Ole A, and Dale, Anders M
Abstract: Accumulating evidence from genome wide association studies (GWAS) suggests an abundance of shared genetic influences among complex human traits and disorders, such as mental disorders. Here we introduce a statistical tool, MiXeR, which quantifies polygenic overlap irrespective of genetic correlation, using GWAS summary statistics. MiXeR results are presented as a Venn diagram of unique and shared polygenic components across traits. At 90% of SNP-heritability explained for each phenotype, MiXeR estimates that 8.3 K variants causally influence schizophrenia and 6.4 K influence bipolar disorder. Among these variants, 6.2 K are shared between the disorders, which have a high genetic correlation. Further, MiXeR uncovers polygenic overlap between schizophrenia and educational attainment. Despite a genetic correlation close to zero, the phenotypes share 8.3 K causal variants, while 2.5 K additional variants influence only educational attainment. By considering the polygenicity, discoverability and heritability of complex phenotypes, MiXeR analysis may improve our understanding of cross-trait genetic architectures.
Published: 2019

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23 results on '"O'Connell, Kevin S."'

1. Fine-mapping genomic loci refines bipolar disorder risk genes

2. Using Polygenic Hazard Scores to Predict Age at Onset of Alzheimer's Disease in Nordic Populations

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

4. Genome-wide association study identifies 48 common genetic variants associated with handedness

5. Genome-wide association study identifies 48 common genetic variants associated with handedness

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

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

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

9. Genome-wide Association Analysis of Parkinson's Disease and Schizophrenia Reveals Shared Genetic Architecture and Identifies Novel Risk Loci.

10. Genome-wide association study identifies 48 common genetic variants associated with handedness.

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

12. Genome-wide association study identifies 48 common genetic variants associated with handedness

13. Genome-wide association study identifies 48 common genetic variants associated with handedness

14. Genome-wide association study identifies 48 common genetic variants associated with handedness

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

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

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

18. Quantifying the Polygenic Architecture of the Human Cerebral Cortex: Extensive Genetic Overlap between Cortical Thickness and Surface Area.

19. Quantifying the Polygenic Architecture of the Human Cerebral Cortex: Extensive Genetic Overlap between Cortical Thickness and Surface Area.

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

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

22. Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation.

23. Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation.

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