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Browsing by Author "Binder, Elisabeth B."
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Item Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors(Elsevier, 2022-02-01) Mullins, Niamh; Kang, JooEun; Campos, Adrian I.; Coleman, Jonathan R. I.; Edwards, Alexis C.; Galfalvy, Hanga; Levey, Daniel F.; Lori, Adriana; Shabalin, Andrey; Starnawska, Anna; Su, Mei-Hsin; Watson, Hunna J.; Adams, Mark; Awasthi, Swapnil; Gandal, Michael; Hafferty, Jonathan D.; Hishimoto, Akitoyo; Kim, Minsoo; Okazaki, Satoshi; Otsuka, Ikuo; Ripke, Stephan; Ware, Erin B.; Bergen, Andrew W.; Berrettini, Wade H.; Bohus, Martin; Brandt, Harry; Chang, Xiao; Chen, Wei J.; Chen, Hsi-Chung; Crawford, Steven; Crow, Scott; DiBlasi, Emily; Duriez, Philibert; Fernández-Aranda, Fernando; Fichter, Manfred M.; Gallinger, Steven; Glatt, Stephen J.; Gorwood, Philip; Guo, Yiran; Hakonarson, Hakon; Halmi, Katherine A.; Hwu, Hai-Gwo; Jain, Sonia; Jamain, Stéphane; Jiménez-Murcia, Susana; Johnson, Craig; Kaplan, Allan S.; Kaye, Walter H.; Keel, Pamela K.; Kennedy, James L.; Klump, Kelly L.; Li, Dong; Liao, Shih-Cheng; Lieb, Klaus; Lilenfeld, Lisa; Liu, Chih-Min; Magistretti, Pierre J.; Marshall, Christian R.; Mitchell, James E.; Monson, Eric T.; Myers, Richard M.; Pinto, Dalila; Powers, Abigail; Ramoz, Nicolas; Roepke, Stefan; Rozanov, Vsevolod; Scherer, Stephen W.; Schmahl, Christian; Sokolowski, Marcus; Strober, Michael; Thornton, Laura M.; Treasure, Janet; Tsuang, Ming T.; Witt, Stephanie H.; Woodside, D. Blake; Yilmaz, Zeynep; Zillich, Lea; Adolfsson, Rolf; Agartz, Ingrid; Air, Tracy M.; Alda, Martin; Alfredsson, Lars; Andreassen, Ole A.; Anjorin, Adebayo; Appadurai, Vivek; Artigas, María Soler; Van der Auwera, Sandra; Azevedo, M. Helena; Bass, Nicholas; Bau, Claiton H. D.; Baune, Bernhard T.; Bellivier, Frank; Berger, Klaus; Biernacka, Joanna M.; Bigdeli, Tim B.; Binder, Elisabeth B.; Boehnke, Michael; Boks, Marco P.; Bosch, Rosa; Braff, David L.; Bryant, Richard; Budde, Monika; Byrne, Enda M.; Cahn, Wiepke; Casas, Miguel; Castelao, Enrique; Cervilla, Jorge A.; Chaumette, Boris; Cichon, Sven; Corvin, Aiden; Craddock, Nicholas; Craig, David; Degenhardt, Franziska; Djurovic, Srdjan; Edenberg, Howard J.; Fanous, Ayman H.; Foo, Jerome C.; Forstner, Andreas J.; Frye, Mark; Fullerton, Janice M.; Gatt, Justine M.; Gejman, Pablo V.; Giegling, Ina; Grabe, Hans J.; Green, Melissa J.; Grevet, Eugenio H.; Grigoroiu-Serbanescu, Maria; Gutierrez, Blanca; Guzman-Parra, Jose; Hamilton, Steven P.; Hamshere, Marian L.; Hartmann, Annette; Hauser, Joanna; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Ising, Marcus; Jones, Ian; Jones, Lisa A.; Jonsson, Lina; Kahn, René S.; Kelsoe, John R.; Kendler, Kenneth S.; Kloiber, Stefan; Koenen, Karestan C.; Kogevinas, Manolis; Konte, Bettina; Krebs, Marie-Odile; Landén, Mikael; Lawrence, Jacob; Leboyer, Marion; Lee, Phil H.; Levinson, Douglas F.; Liao, Calwing; Lissowska, Jolanta; Lucae, Susanne; Mayoral, Fermin; McElroy, Susan L.; McGrath, Patrick; McGuffin, Peter; McQuillin, Andrew; Medland, Sarah E.; Mehta, Divya; Melle, Ingrid; Milaneschi, Yuri; Mitchell, Philip B.; Molina, Esther; Morken, Gunnar; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Nievergelt, Caroline; Nimgaonkar, Vishwajit; Nöthen, Markus M.; O’Donovan, Michael C.; Ophoff, Roel A.; Owen, Michael J.; Pato, Carlos; Pato, Michele T.; Penninx, Brenda W. J. H.; Pimm, Jonathan; Pistis, Giorgio; Potash, James B.; Power, Robert A.; Preisig, Martin; Quested, Digby; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Ribasés , Marta; Richarte, Vanesa; Rietschel, Marcella; Rivera, Margarita; Roberts, Andrea; Roberts, Gloria; Rouleau, Guy A.; Rovaris, Diego L.; Rujescu, Dan; Sánchez-Mora, Cristina; Sanders, Alan R.; Schofield, Peter R.; Schulze, Thomas G.; Scott, Laura J.; Serretti, Alessandro; Shi, Jianxin; Shyn, Stanley I.; Sirignano, Lea; Sklar, Pamela; Smeland, Olav B.; Smoller, Jordan W.; Sonuga-Barke, Edmund J. S.; Spalletta, Gianfranco; Strauss, John S.; Świątkowska, Beata; Trzaskowski, Maciej; Turecki, Gustavo; Vilar-Ribó, Laura; Vincent, John B.; Völzke, Henry; Walters, James T. R.; Weickert, Cynthia Shannon; Weickert, Thomas W.; Weissman, Myrna M.; Williams, Leanne M.; Wray, Naomi R.; Zai, Clement C.; Ashley-Koch, Allison E.; Beckham, Jean C.; Hauser, Elizabeth R.; Hauser, Michael A.; Kimbrel, Nathan A.; Lindquist, Jennifer H.; McMahon, Benjamin; Oslin, David W.; Qin, Xuejun; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Eating Disorders Working Group of the Psychiatric Genomics Consortium; German Borderline Genomics Consortium; MVP Suicide Exemplar Workgroup; VA Million Veteran Program; Medical & Molecular Genetics, School of MedicineBACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Item Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group(Springer Nature, 2021) Jia, Tianye; Chu, Congying; Liu, Yun; Van Dongen, Jenny; Papastergios, Evangelos; Armstrong, Nicola J.; Bastin, Mark E.; Carrillo-Roa, Tania; den Braber, Anouk; Harris, Mathew; Jansen, Rick; Liu, Jingyu; Luciano, Michelle; Ori, Anil P.S.; Santiañez, Roberto Roiz; Ruggeri, Barbara; Sarkisyan, Daniil; Shin, Jean; Sungeun, Kim; Tordesillas Gutiérrez, Diana; van't Ent, Dennis; Ames, David; Artiges, Eric; Bakalkin, Georgy; Banaschewski, Tobias; Bokde, Arun L.W.; Brodaty, Henry; Bromberg, Uli; Brouwer, Rachel; Büchel, Christian; Burke Quinlan, Erin; Cahn, Wiepke; de Zubicaray, Greig I.; Ehrlich, Stefan; Ekström, Tomas J.; Flor, Herta; Fröhner, Juliane H.; Frouin, Vincent; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Hoare, Jacqueline; Ittermann, Bernd; Jahanshad, Neda; Jiang, Jiyang; Kwok, John B.; Martin, Nicholas G.; Martinot, Jean-Luc; Mather, Karen A.; McMahon, Katie L.; McRae, Allan F.; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomáš; Poustka, Luise; Sämann, Philipp G.; Schofield, Peter R.; Smolka, Michael N.; Stein, Dan J.; Strike, Lachlan T.; Teeuw, Jalmar; Thalamuthu, Anbupalam; Trollor, Julian; Walter, Henrik; Wardlaw, Joanna M.; Wen, Wei; Whelan, Robert; Apostolova, Liana G.; Binder, Elisabeth B.; Boomsma, Dorret I.; Calhoun, Vince; Crespo-Facorro, Benedicto; Deary, Ian J.; Hulshoff Pol, Hilleke; Ophoff, Roel A.; Pausova, Zdenka; Sachdev, Perminder S.; Saykin, Andrew; Wright, Margaret J.; Thompson, Paul M.; Schumann, Gunter; Desrivières, Sylvane; Radiology and Imaging Sciences, School of MedicineDNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.Item GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors(American Psychiatric Association, 2023) Docherty, Anna R.; Mullins, Niamh; Ashley-Koch, Allison E.; Qin, Xuejun; Coleman, Jonathan R. I.; Shabalin, Andrey; Kang, JooEun; Murnyak, Balasz; Wendt, Frank; Adams, Mark; Campos, Adrian I.; DiBlasi, Emily; Fullerton, Janice M.; Kranzler, Henry R.; Bakian, Amanda V.; Monson, Eric T.; Rentería, Miguel E.; Walss-Bass, Consuelo; Andreassen, Ole A.; Behera, Chittaranjan; Bulik, Cynthia M.; Edenberg, Howard J.; Kessler, Ronald C.; Mann, J. John; Nurnberger, John I., Jr.; Pistis, Giorgio; Streit, Fabian; Ursano, Robert J.; Polimanti, Renato; Dennis, Michelle; Garrett, Melanie; Hair, Lauren; Harvey, Philip; Hauser, Elizabeth R.; Hauser, Michael A.; Huffman, Jennifer; Jacobson, Daniel; Madduri, Ravi; McMahon, Benjamin; Oslin, David W.; Trafton, Jodie; Awasthi, Swapnil; Berrettini, Wade H.; Bohus, Martin; Chang, Xiao; Chen, Hsi-Chung; Chen, Wei J.; Christensen, Erik D.; Crow, Scott; Duriez, Philibert; Edwards, Alexis C.; Fernández-Aranda, Fernando; Galfalvy, Hanga; Gandal, Michael; Gorwood, Philip; Guo, Yiran; Hafferty, Jonathan D.; Hakonarson, Hakon; Halmi, Katherine A.; Hishimoto, Akitoyo; Jain, Sonia; Jamain, Stéphane; Jiménez-Murcia, Susana; Johnson, Craig; Kaplan, Allan S.; Kaye, Walter H.; Keel, Pamela K.; Kennedy, James L.; Kim, Minsoo; Klump, Kelly L.; Levey, Daniel F.; Li, Dong; Liao, Shih-Cheng; Lieb, Klaus; Lilenfeld, Lisa; Marshall, Christian R.; Mitchell, James E.; Okazaki, Satoshi; Otsuka, Ikuo; Pinto, Dalila; Powers, Abigail; Ramoz, Nicolas; Ripke, Stephan; Roepke, Stefan; Rozanov, Vsevolod; Scherer, Stephen W.; Schmahl, Christian; Sokolowski, Marcus; Starnawska, Anna; Strober, Michael; Su, Mei-Hsin; Thornton, Laura M.; Treasure, Janet; Ware, Erin B.; Watson, Hunna J.; Witt, Stephanie H.; Woodside, D. Blake; Yilmaz, Zeynep; Zillich, Lea; Adolfsson, Rolf; Agartz, Ingrid; Alda, Martin; Alfredsson, Lars; Appadurai, Vivek; Artigas, María Soler; Van der Auwera, Sandra; Azevedo, M. Helena; Bass, Nicholas; Bau, Claiton H. D.; Baune, Bernhard T.; Bellivier, Frank; Berger, Klaus; Biernacka, Joanna M.; Bigdeli, Tim B.; Binder, Elisabeth B.; Boehnke, Michael; Boks, Marco P.; Braff, David L.; Bryant, Richard; Budde, Monika; Byrne, Enda M.; Cahn, Wiepke; Castelao, Enrique; Cervilla, Jorge A.; Chaumette, Boris; Corvin, Aiden; Craddock, Nicholas; Djurovic, Srdjan; Foo, Jerome C.; Forstner, Andreas J.; Frye, Mark; Gatt, Justine M.; Giegling, Ina; Grabe, Hans J.; Green, Melissa J.; Grevet, Eugenio H.; Grigoroiu-Serbanescu, Maria; Gutierrez, Blanca; Guzman-Parra, Jose; Hamshere, Marian L.; Hartmann, Annette M.; Hauser, Joanna; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Ising, Marcus; Jones, Ian; Jones, Lisa A.; Jonsson, Lina; Kahn, René S.; Kelsoe, John R.; Kendler, Kenneth S.; Kloiber, Stefan; Koenen, Karestan C.; Kogevinas, Manolis; Krebs, Marie-Odile; Landén, Mikael; Leboyer, Marion; Lee, Phil H.; Levinson, Douglas F.; Liao, Calwing; Lissowska, Jolanta; Mayoral, Fermin; McElroy, Susan L.; McGrath, Patrick; McGuffin, Peter; McQuillin, Andrew; Mehta, Divya; Melle, Ingrid; Mitchell, Philip B.; Molina, Esther; Morken, Gunnar; Nievergelt, Caroline; Nöthen, Markus M.; O'Donovan, Michael C.; Ophoff, Roel A.; Owen, Michael J.; Pato, Carlos; Pato, Michele T.; Penninx, Brenda W. J. H.; Potash, James B.; Power, Robert A.; Preisig, Martin; Quested, Digby; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Ribasés, Marta; Richarte, Vanesa; Rietschel, Marcella; Rivera, Margarita; Roberts, Andrea; Roberts, Gloria; Rouleau, Guy A.; Rovaris, Diego L.; Sanders, Alan R.; Schofield, Peter R.; Schulze, Thomas G.; Scott, Laura J.; Serretti, Alessandro; Shi, Jianxin; Sirignano, Lea; Sklar, Pamela; Smeland, Olav B.; Smoller, Jordan W.; Sonuga-Barke, Edmund J. S.; Trzaskowski, Maciej; Tsuang, Ming T.; Turecki, Gustavo; Vilar-Ribó, Laura; Vincent, John B.; Völzke, Henry; Walters, James T. R.; Weickert, Cynthia Shannon; Weickert, Thomas W.; Weissman, Myrna M.; Williams, Leanne M.; Wray, Naomi R.; Zai, Clement C.; Agerbo, Esben; Børglum, Anders D.; Breen, Gerome; Demontis, Ditte; Erlangsen, Annette; Gelernter, Joel; Glatt, Stephen J.; Hougaard, David M.; Hwu, Hai-Gwo; Kuo, Po-Hsiu; Lewis, Cathryn M.; Li, Qingqin S.; Liu, Chih-Min; Martin, Nicholas G.; McIntosh, Andrew M.; Medland, Sarah E.; Mors, Ole; Nordentoft, Merete; Olsen, Catherine M.; Porteous, David; Smith, Daniel J.; Stahl, Eli A.; Stein, Murray B.; Wasserman, Danuta; Werge, Thomas; Whiteman, David C.; Willour, Virginia; VA Million Veteran Program (MVP); MVP Suicide Exemplar Workgroup; Suicide Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Eating Disorder Working Group of the Psychiatric Genomics Consortium; German Borderline Genomics Consortium; Coon, Hilary; Beckham, Jean C.; Kimbrel, Nathan A.; Ruderfer, Douglas M.; Psychiatry, School of MedicineObjective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.