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914 results on '"Mortensen, Preben B"'

1. Genome-wide by Environment Interaction Study of Stressful Life Events and Hospital-Treated Depression in the iPSYCH2012 Sample

Author

Suppli, Nis P, Andersen, Klaus K, Agerbo, Esben, Rajagopal, Veera M, Appadurai, Vivek, Coleman, Jonathan RI, Breen, Gerome, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Pedersen, Carsten B, Pedersen, Marianne G, Thompson, Wesley K, Munk-Olsen, Trine, Benros, Michael E, Als, Thomas D, Grove, Jakob, Werge, Thomas, Børglum, Anders D, Hougaard, David M, Mors, Ole, Nordentoft, Merete, Mortensen, Preben B, and Musliner, Katherine L

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Depression, Mental Health, Mental health, Good Health and Well Being, Case-cohort studies, GXE, Register-based research, Stress
Abstract

BackgroundResearchers have long investigated a hypothesized interaction between genetic risk and stressful life events in the etiology of depression, but studies on the topic have yielded inconsistent results.MethodsWe conducted a genome-wide by environment interaction study (GWEIS) in 18,532 patients with depression from hospital-based settings and 20,184 population controls. All individuals were drawn from the iPSYCH2012 case-cohort study, a nationally representative sample identified from Danish national registers. Information on stressful life events including family disruption, serious medical illness, death of a first-degree relative, parental disability, and child maltreatment was identified from the registers and operationalized as a time-varying count variable. Hazard ratios for main and interaction effects were estimated using Cox regressions weighted to accommodate the case-cohort design. Our replication sample included 22,880 depression cases and 50,378 controls from the UK Biobank.ResultsThe GWEIS in the iPSYCH2012 sample yielded three novel, genome-wide-significant (p < 5 × 10-8) loci located in the ABCC1 gene (rs56076205, p = 3.7 × 10-10), the AKAP6 gene (rs3784187, p = 1.2 × 10-8), and near the MFSD1 gene (rs340315, p = 4.5 × 10-8). No hits replicated in the UK Biobank (rs56076205: p = .87; rs3784187: p = .93; rs340315: p = .71).ConclusionsIn this large, population-based GWEIS, we did not find any replicable hits for interaction. Future gene-by-stress research in depression should focus on establishing even larger collaborative GWEISs to attain sufficient power.

Published
2022

2. ADuLT: An efficient and robust time-to-event GWAS

Author

Pedersen, Emil M., Agerbo, Esben, Plana-Ripoll, Oleguer, Steinbach, Jette, Krebs, Morten D., Hougaard, David M., Werge, Thomas, Nordentoft, Merete, Børglum, Anders D., Musliner, Katherine L., Ganna, Andrea, Schork, Andrew J., Mortensen, Preben B., McGrath, John J., Privé, Florian, and Vilhjálmsson, Bjarni J.

Published
2023
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4. Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses

Author

Als, Thomas D., Kurki, Mitja I., Grove, Jakob, Voloudakis, Georgios, Therrien, Karen, Tasanko, Elisa, Nielsen, Trine Tollerup, Naamanka, Joonas, Veerapen, Kumar, Levey, Daniel F., Bendl, Jaroslav, Bybjerg-Grauholm, Jonas, Zeng, Biao, Demontis, Ditte, Rosengren, Anders, Athanasiadis, Georgios, Bækved-Hansen, Marie, Qvist, Per, Bragi Walters, G., Thorgeirsson, Thorgeir, Stefánsson, Hreinn, Musliner, Katherine L., Rajagopal, Veera M., Farajzadeh, Leila, Thirstrup, Janne, Vilhjálmsson, Bjarni J., McGrath, John J., Mattheisen, Manuel, Meier, Sandra, Agerbo, Esben, Stefánsson, Kári, Nordentoft, Merete, Werge, Thomas, Hougaard, David M., Mortensen, Preben B., Stein, Murray B., Gelernter, Joel, Hovatta, Iiris, Roussos, Panos, Daly, Mark J., Mors, Ole, Palotie, Aarno, and Børglum, Anders D.

Published
2023
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5. Maternal pregnancy-related infections and autism spectrum disorder—the genetic perspective

Author

Nudel, Ron, Thompson, Wesley K, Børglum, Anders D, Hougaard, David M, Mortensen, Preben B, Werge, Thomas, Nordentoft, Merete, and Benros, Michael E

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Autism, Human Genome, Pediatric, Mental Health, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Genetics, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Mental health, Animals, Autism Spectrum Disorder, Cohort Studies, Communication, Female, Humans, Mothers, Phenotype, Pregnancy, Public Health and Health Services, Psychology, Clinical sciences, Biological psychology
Abstract

Autism spectrum disorder (ASD) refers to a group of neurodevelopmental disorders which include deficits in behavior, social interaction and communication. ASD has a complex genetic architecture, and it is also influenced by certain environmental exposures. Both types of predisposing factors may be related to immunological mechanisms, involving, for example, immune system genes and infections. Past studies have shown an association between infections occurring during the pregnancy in the mother and increased risk of ASD in the child, an observation which has received recent support from experimental animal studies of ASD-like behavior. The aim of this study was to study the genetic contribution to this effect. We employed genetic correlation analyses across potential ASD subtypes stratified on the basis of maternal pregnancy-related infections within the iPSYCH ASD case-cohort sample, as well as a case-case GWAS. We validated the trends of the genetic correlation analyses observed in our sample using GWAS summary statistics from the PGC ASD study (excluding iPSYCH). The genetic correlation between ASD with a history of maternal pregnancy-related infections and ASD without a history of maternal infections in iPSYCH was rg = 0.3811. We obtained a similar estimate between the former and the PGC ASD phenotype (rg = 0.3997). Both estimates are lower compared to the genetic correlation between ASD without a history of maternal infections and the PGC ASD phenotype (rg = 0.6735), and between ASD with a history of maternal infections occurring only more than 2 months following childbirth and the PGC ASD phenotype (rg = 0.6293). Additionally, we observed genetic variance between the two main ASD phenotypes using summary statistics from the case-case GWAS in iPSYCH (h2cc = 0.1059), indicating genome-wide differences between the phenotypes. Our results suggest potentially different etiologies of ASD based on a history of maternal pregnancy-related infections, which may, in part, be genetic. This highlights the relevance of maternal pregnancy-related infections to genetic studies of ASD and provides new insights into the molecular underpinnings of ASD.

Published
2022

6. A large-scale genome-wide association study meta-analysis of cannabis use disorder.

Author

Johnson, Emma C, Demontis, Ditte, Thorgeirsson, Thorgeir E, Walters, Raymond K, Polimanti, Renato, Hatoum, Alexander S, Sanchez-Roige, Sandra, Paul, Sarah E, Wendt, Frank R, Clarke, Toni-Kim, Lai, Dongbing, Reginsson, Gunnar W, Zhou, Hang, He, June, Baranger, David AA, Gudbjartsson, Daniel F, Wedow, Robbee, Adkins, Daniel E, Adkins, Amy E, Alexander, Jeffry, Bacanu, Silviu-Alin, Bigdeli, Tim B, Boden, Joseph, Brown, Sandra A, Bucholz, Kathleen K, Bybjerg-Grauholm, Jonas, Corley, Robin P, Degenhardt, Louisa, Dick, Danielle M, Domingue, Benjamin W, Fox, Louis, Goate, Alison M, Gordon, Scott D, Hack, Laura M, Hancock, Dana B, Hartz, Sarah M, Hickie, Ian B, Hougaard, David M, Krauter, Kenneth, Lind, Penelope A, McClintick, Jeanette N, McQueen, Matthew B, Meyers, Jacquelyn L, Montgomery, Grant W, Mors, Ole, Mortensen, Preben B, Nordentoft, Merete, Pearson, John F, Peterson, Roseann E, Reynolds, Maureen D, Rice, John P, Runarsdottir, Valgerdur, Saccone, Nancy L, Sherva, Richard, Silberg, Judy L, Tarter, Ralph E, Tyrfingsson, Thorarinn, Wall, Tamara L, Webb, Bradley T, Werge, Thomas, Wetherill, Leah, Wright, Margaret J, Zellers, Stephanie, Adams, Mark J, Bierut, Laura J, Boardman, Jason D, Copeland, William E, Farrer, Lindsay A, Foroud, Tatiana M, Gillespie, Nathan A, Grucza, Richard A, Harris, Kathleen Mullan, Heath, Andrew C, Hesselbrock, Victor, Hewitt, John K, Hopfer, Christian J, Horwood, John, Iacono, William G, Johnson, Eric O, Kendler, Kenneth S, Kennedy, Martin A, Kranzler, Henry R, Madden, Pamela AF, Maes, Hermine H, Maher, Brion S, Martin, Nicholas G, McGue, Matthew, McIntosh, Andrew M, Medland, Sarah E, Nelson, Elliot C, Porjesz, Bernice, Riley, Brien P, Stallings, Michael C, Vanyukov, Michael M, Vrieze, Scott, Psychiatric Genomics Consortium Substance Use Disorders Workgroup, Davis, Lea K, Bogdan, Ryan, Gelernter, Joel, and Edenberg, Howard J

Subjects
Psychiatric Genomics Consortium Substance Use Disorders Workgroup, Humans, Marijuana Abuse, Risk, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

BackgroundVariation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder.MethodsTo conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations.FindingsWe identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10-9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86-0·93, p=6·46 × 10-9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10-21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia.InterpretationThese findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder.FundingNational Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Published
2020

7. The genetic architecture of sporadic and multiple consecutive miscarriage.

Author

Laisk, Triin, Soares, Ana Luiza G, Ferreira, Teresa, Painter, Jodie N, Censin, Jenny C, Laber, Samantha, Bacelis, Jonas, Chen, Chia-Yen, Lepamets, Maarja, Lin, Kuang, Liu, Siyang, Millwood, Iona Y, Ramu, Avinash, Southcombe, Jennifer, Andersen, Marianne S, Yang, Ling, Becker, Christian M, Børglum, Anders D, Gordon, Scott D, Bybjerg-Grauholm, Jonas, Helgeland, Øyvind, Hougaard, David M, Jin, Xin, Johansson, Stefan, Juodakis, Julius, Kartsonaki, Christiana, Kukushkina, Viktorija, Lind, Penelope A, Metspalu, Andres, Montgomery, Grant W, Morris, Andrew P, Mors, Ole, Mortensen, Preben B, Njølstad, Pål R, Nordentoft, Merete, Nyholt, Dale R, Lippincott, Margaret, Seminara, Stephanie, Salumets, Andres, Snieder, Harold, Zondervan, Krina, Werge, Thomas, Chen, Zhengming, Conrad, Donald F, Jacobsson, Bo, Li, Liming, Martin, Nicholas G, Neale, Benjamin M, Nielsen, Rasmus, Walters, Robin G, Granne, Ingrid, Medland, Sarah E, Mägi, Reedik, Lawlor, Deborah A, and Lindgren, Cecilia M

Abstract

Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.

Published
2020

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

Author

Consortium, Cross-Disorder Group of the Psychiatric Genomics, Lee, Phil H, Anttila, Verneri, Won, Hyejung, Feng, Yen-Chen A, Rosenthal, Jacob, Zhu, Zhaozhong, Tucker-Drob, Elliot M, Nivard, Michel G, Grotzinger, Andrew D, Posthuma, Danielle, Wang, Meg M-J, Yu, Dongmei, Stahl, Eli A, Walters, Raymond K, Anney, Richard JL, Duncan, Laramie E, Ge, Tian, Adolfsson, Rolf, Banaschewski, Tobias, Belangero, Sintia, Cook, Edwin H, Coppola, Giovanni, Derks, Eske M, Hoekstra, Pieter J, Kaprio, Jaakko, Keski-Rahkonen, Anna, Kirov, George, Kranzler, Henry R, Luykx, Jurjen J, Rohde, Luis A, Zai, Clement C, Agerbo, Esben, Arranz, MJ, Asherson, Philip, Bækvad-Hansen, Marie, Baldursson, Gísli, Bellgrove, Mark, Belliveau, Richard A, Buitelaar, Jan, Burton, Christie L, Bybjerg-Grauholm, Jonas, Casas, Miquel, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Cormand, Bru, Crosbie, Jennifer, Dalsgaard, Søren, Demontis, Ditte, Doyle, Alysa E, Dumont, Ashley, Elia, Josephine, Grove, Jakob, Gudmundsson, Olafur O, Haavik, Jan, Hakonarson, Hakon, Hansen, Christine S, Hartman, Catharina A, Hawi, Ziarih, Hervás, Amaia, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Leung, Patrick WL, Loo, Sandra K, Martin, Joanna, Martin, Alicia R, McGough, James J, Medland, Sarah E, Moran, Jennifer L, Mors, Ole, Mortensen, Preben B, Oades, Robert D, Palmer, Duncan S, Pedersen, Carsten B, Pedersen, Marianne G, Peters, Triinu, Poterba, Timothy, Poulsen, Jesper B, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Satterstrom, F Kyle, Schachar, Russell, Artigas, Maria Soler, Steinberg, Stacy, Stefansson, Hreinn, Turley, Patrick, Walters, G Bragi, Team, 23andMe Research, Werge, Thomas, Zayats, Tetyana, and Arking, Dan E

Subjects
Neurosciences, Serious Mental Illness, Human Genome, Schizophrenia, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Genetics, Pediatric, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mental Disorders, Neurogenesis, Quantitative Trait Loci, Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu, Cross-Disorder Group of the Psychiatric Genomics Consortium, GWAS, Psychiatric genetics, cross-disorder genetics, functional genomics, gene expression, genetic architecture, genetic correlation, neurodevelopment, pleiotropy, psychiatric disorders, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Published
2019

9. Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Author

Ripke, Stephan, Neale, Benjamin M., Corvin, Aiden, Walters, James T.R., Farh, Kai-How, Holmans, Peter A., Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A., Jr., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Bigdeli, Tim B., Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C.K., Chan, Ronald Y.L., Chen, Eric Y.H., Cheng, Wei, Cheung, Eric FC., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Davis, Kenneth L., Degenhardt, Franziska, Del Favero, Jurgen, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H., Farrell, Martilias S., Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Lee, Jimmy, Lee, S. Hong, Legge, Sophie E., Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Magnusson, Patrik K.E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Morris, Derek W., Mors, Ole, Murphy, Kieran C., Murray, Robin M., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O'Callaghan, Eadbhard, O'Dushlaine, Colm, O'Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Van Os, Jim, Pantelis, Christos, Papadimitriou, George N., Papiol, Sergi, Parkhomenko, Elena, Pato, Michele T., Paunio, Tiina, Pejovic-Milovancevic, Milica, Perkins, Diana O., Pietiläinen, Olli, Pimm, Jonathan, Pocklington, Andrew J., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Rasmussen, Henrik B., Reichenberg, Abraham, Reimers, Mark A., Richards, Alexander L., Roffman, Joshua L., Roussos, Panos, Ruderfer, Douglas M., Salomaa, Veikko, Sanders, Alan R., Schall, Ulrich, Schubert, Christian R., Schulze, Thomas G., Schwab, Sibylle G., Scolnick, Edward M., Scott, Rodney J., Seidman, Larry J., Shi, Jianxin, Sigurdsson, Engilbert, Silagadze, Teimuraz, Silverman, Jeremy M., Sim, Kang, Slominsky, Petr, Smoller, Jordan W., So, Hon-Cheong, Spencer, Chris C.A., Stahl, Eli A., Stefansson, Hreinn, Steinberg, Stacy, Stogmann, Elisabeth, Straub, Richard E., Strengman, Eric, Strohmaier, Jana, Stroup, T Scott, Subramaniam, Mythily, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Söderman, Erik, Thirumalai, Srinivas, Toncheva, Draga, Tosato, Sarah, Veijola, Juha, Waddington, John, Walsh, Dermot, Wang, Dai, Wang, Qiang, Webb, Bradley T., Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H.M., Wormley, Brandon K., Xi, Hualin Simon, Zai, Clement C., Zheng, Xuebin, Zimprich, Fritz, Wray, Naomi R., Stefansson, Kari, Visscher, Peter M., Adolfsson, Rolf, Andreassen, Ole A., Blackwood, Douglas H.R., Bramon, Elvira, Buxbaum, Joseph D., Børglum, Anders D., Cichon, Sven, Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., McQuillin, Andrew, Moran, Jennifer L., Mortensen, Preben B., Mowry, Bryan J., Nöthen, Markus M., Ophoff, Roel A., Owen, Michael J., Palotie, Aarno, Pato, Carlos N., Petryshen, Tracey L., Posthuma, Danielle, Rietschel, Marcella, Riley, Brien P., Rujescu, Dan, Sham, Pak C., Sklar, Pamela, St Clair, David, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Sullivan, Patrick F., O'Donovan, Michael C., Qin, Shengying, Sawa, Akira, Kahn, Rene, Hong, Kyung Sue, Shi, Wenzhao, Tsuang, Ming, Itokawa, Masanari, Feng, Gang, Glatt, Stephen J., Ma, Xiancang, Tang, Jinsong, Ruan, Yunfeng, Liu, Ruize, Zhu, Feng, Horiuchi, Yasue, Lee, Byung Dae, Joo, Eun-Jeong, Myung, Woojae, Ha, Kyooseob, Won, Hong-Hee, Baek, Ji Hyung, Chung, Young Chul, Kim, Sung-Wan, Kusumawardhani, Agung, Chen, Wei J., Hwu, Hai-Gwo, Hishimoto, Akitoyo, Otsuka, Ikuo, Sora, Ichiro, Toyota, Tomoko, Yoshikawa, Takeo, Kunugi, Hiroshi, Hattori, Kotaro, Ishiwata, Sayuri, Numata, Shusuke, Ohmori, Tetsuro, Arai, Makoto, Ozeki, Yuji, Fujii, Kumiko, Kim, Se Joo, Lee, Heon-Jeong, Ahn, Yong Min, Kim, Se Hyun, Akiyama, Kazufumi, Shimoda, Kazutaka, Kinoshita, Makoto, Hsu, Yu-Han H., Pintacuda, Greta, Nacu, Eugeniu, Kim, April, Tsafou, Kalliopi, Petrossian, Natalie, Crotty, William, Suh, Jung Min, Riseman, Jackson, Martin, Jacqueline M., Biagini, Julia C., Mena, Daya, Ching, Joshua K.T., Malolepsza, Edyta, Li, Taibo, Singh, Tarjinder, Ge, Tian, Egri, Shawn B., Tanenbaum, Benjamin, Stanclift, Caroline R., Apffel, Annie M., Carr, Steven A., Schenone, Monica, Jaffe, Jake, Fornelos, Nadine, Eggan, Kevin C., and Lage, Kasper

Published
2023
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10. Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups

Author

Mattheisen, Manuel, Grove, Jakob, Als, Thomas D., Martin, Joanna, Voloudakis, Georgios, Meier, Sandra, Demontis, Ditte, Bendl, Jaroslav, Walters, Raymond, Carey, Caitlin E., Rosengren, Anders, Strom, Nora I., Hauberg, Mads Engel, Zeng, Biao, Hoffman, Gabriel, Zhang, Wen, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Agerbo, Esben, Cormand, Bru, Nordentoft, Merete, Werge, Thomas, Mors, Ole, Hougaard, David M., Buxbaum, Joseph D., Faraone, Stephen V., Franke, Barbara, Dalsgaard, Søren, Mortensen, Preben B., Robinson, Elise B., Roussos, Panos, Neale, Benjamin M., Daly, Mark J., and Børglum, Anders D.

Published
2022
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11. Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset: a case-cohort study

Author

Sánchez, Xabier Calle, Montalbano, Simone, Vaez, Morteza, Krebs, Morten Dybdahl, Byberg-Grauholm, Jonas, Mortensen, Preben B, Børglum, Anders D, Hougaard, David M, Nordentoft, Merete, Geschwind, Daniel H, Buil, Alfonso, Schork, Andrew J, Thompson, Wesley K, Raznahan, Armin, Helenius, Dorte, Werge, Thomas, and Ingason, Andrés

Published
2023
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12. Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder

Author

Rajagopal, Veera M., Duan, Jinjie, Vilar-Ribó, Laura, Grove, Jakob, Zayats, Tetyana, Ramos-Quiroga, J. Antoni, Satterstrom, F. Kyle, Artigas, María Soler, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Als, Thomas D., Rosengren, Anders, Daly, Mark J., Neale, Benjamin M., Nordentoft, Merete, Werge, Thomas, Mors, Ole, Hougaard, David M., Mortensen, Preben B., Ribasés, Marta, Børglum, Anders D., and Demontis, Ditte

Published
2022
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13. A large-scale genomic investigation of susceptibility to infection and its association with mental disorders in the Danish population.

Author

Nudel, Ron, Wang, Yunpeng, Appadurai, Vivek, Schork, Andrew J, Buil, Alfonso, Agerbo, Esben, Bybjerg-Grauholm, Jonas, Børglum, Anders D, Daly, Mark J, Mors, Ole, Hougaard, David M, Mortensen, Preben B, Werge, Thomas, Nordentoft, Merete, Thompson, Wesley K, and Benros, Michael E

Subjects
Humans, Genetic Predisposition to Disease, Genetic Markers, Registries, Incidence, Logistic Models, Mental Disorders, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Denmark, Female, Male, Genome-Wide Association Study, Infections, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Infections and mental disorders are two of the major global disease burdens. While correlations between mental disorders and infections have been reported, the possible genetic links between them have not been assessed in large-scale studies. Moreover, the genetic basis of susceptibility to infection is largely unknown, as large-scale genome-wide association studies of susceptibility to infection have been lacking. We utilized a large Danish population-based sample (N = 65,534) linked to nationwide population-based registers to investigate the genetic architecture of susceptibility to infection (heritability estimation, polygenic risk analysis, and a genome-wide association study (GWAS)) and examined its association with mental disorders (comorbidity analysis and genetic correlation). We found strong links between having at least one psychiatric diagnosis and the occurrence of infection (P = 2.16 × 10-208, OR = 1.72). The SNP heritability of susceptibility to infection ranged from ~2 to ~7% in samples of differing psychiatric diagnosis statuses (suggesting the environment as a major contributor to susceptibility), and polygenic risk scores moderately but significantly explained infection status in an independent sample. We observed a genetic correlation of 0.496 (P = 2.17 × 10-17) between a diagnosis of infection and a psychiatric diagnosis. While our GWAS did not identify genome-wide significant associations, we found 90 suggestive (P ≤ 10-5) associations for susceptibility to infection. Our findings suggest a genetic component in susceptibility to infection and indicate that the occurrence of infections in individuals with mental illness may be in part genetically driven.

Published
2019

14. Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Author

Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B., Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A., Hall, Lynsey S., Lam, Max, Watanabe, Kyoko, Frei, Oleksandr, Ge, Tian, Harwood, Janet C., Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L., Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G., Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z., Alptekin, Köksal, Als, Thomas D., Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A., Bass, Nicholas J., Begemann, Martin, Belliveau, Richard A., Bene, Judit, Benyamin, Beben, Bergen, Sarah E., Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Bressan, Rodrigo Affonseca, Bromet, Evelyn J., Bruggeman, Richard, Buckley, Peter F., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J., Calkins, Monica E., Carr, Vaughan J., Castle, David, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C. K., Chaumette, Boris, Cheng, Wei, Cheung, Eric F. C., Chong, Siow Ann, Cohen, David, Consoli, Angèle, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L., de Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E., Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanás, Lourdes, Faraone, Stephen V., Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B., Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S., Giannitelli, Marianna, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., González Peñas, Javier, González-Pinto, Ana, Gopal, Srihari, Gratten, Jacob, Green, Michael F., Greenwood, Tiffany A., Guillin, Olivier, Gülöksüz, Sinan, Gur, Raquel E., Gur, Ruben C., Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Haroutunian, Vahram, Hartmann, Annette M., Harvey, Carol, Hayward, Caroline, Henskens, Frans A., Herms, Stefan, Hoffmann, Per, Howrigan, Daniel P., Ikeda, Masashi, Iyegbe, Conrad, Joa, Inge, Julià, Antonio, Kähler, Anna K., Kam-Thong, Tony, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Kebir, Oussama, Keller, Matthew C., Kelly, Brian J., Khrunin, Andrey, Kim, Sung-Wan, Klovins, Janis, Kondratiev, Nikolay, Konte, Bettina, Kraft, Julia, Kubo, Michiaki, Kučinskas, Vaidutis, Kučinskiene, Zita Ausrele, Kusumawardhani, Agung, Kuzelova-Ptackova, Hana, Landi, Stefano, Lazzeroni, Laura C., Lee, Phil H., Legge, Sophie E., Lehrer, Douglas S., Lencer, Rebecca, Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Light, Gregory A., Limborska, Svetlana, Liu, Chih-Min, Lönnqvist, Jouko, Loughland, Carmel M., Lubinski, Jan, Luykx, Jurjen J., Lynham, Amy, Macek, Jr, Milan, Mackinnon, Andrew, Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Malaspina, Dolores, Mallet, Jacques, Marder, Stephen R., Marsal, Sara, Martin, Alicia R., Martorell, Lourdes, Mattheisen, Manuel, McCarley, Robert W., McDonald, Colm, McGrath, John J., Medeiros, Helena, Meier, Sandra, Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mitjans, Marina, Molden, Espen, Molina, Esther, Molto, María Dolores, Mondelli, Valeria, Moreno, Carmen, Morley, Christopher P., Muntané, Gerard, Murphy, Kieran C., Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Nikitina-Zake, Liene, Noto, Cristiano, Nuechterlein, Keith H., O’Brien, Niamh Louise, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Ota, Vanessa Kiyomi, Pantelis, Christos, Papadimitriou, George N., Parellada, Mara, Paunio, Tiina, Pellegrino, Renata, Periyasamy, Sathish, Perkins, Diana O., Pfuhlmann, Bruno, Pietiläinen, Olli, Pimm, Jonathan, Porteous, David, Powell, John, Quattrone, Diego, Quested, Digby, Radant, Allen D., Rampino, Antonio, Rapaport, Mark H., Rautanen, Anna, Reichenberg, Abraham, Roe, Cheryl, Roffman, Joshua L., Roth, Julian, Rothermundt, Matthias, Rutten, Bart P. F., Saker-Delye, Safaa, Salomaa, Veikko, Sanjuan, Julio, Santoro, Marcos Leite, Savitz, Adam, Schall, Ulrich, Scott, Rodney J., Seidman, Larry J., Sharp, Sally Isabel, Shi, Jianxin, Siever, Larry J., Sigurdsson, Engilbert, Sim, Kang, Skarabis, Nora, Slominsky, Petr, So, Hon-Cheong, Sobell, Janet L., Söderman, Erik, Stain, Helen J., Steen, Nils Eiel, Steixner-Kumar, Agnes A., Stögmann, Elisabeth, Stone, William S., Straub, Richard E., Streit, Fabian, Strengman, Eric, Stroup, T. Scott, Subramaniam, Mythily, Sugar, Catherine A., Suvisaari, Jaana, Svrakic, Dragan M., Swerdlow, Neal R., Szatkiewicz, Jin P., Ta, Thi Minh Tam, Takahashi, Atsushi, Terao, Chikashi, Thibaut, Florence, Toncheva, Draga, Tooney, Paul A., Torretta, Silvia, Tosato, Sarah, Tura, Gian Battista, Turetsky, Bruce I., Üçok, Alp, Vaaler, Arne, van Amelsvoort, Therese, van Winkel, Ruud, Veijola, Juha, Waddington, John, Walter, Henrik, Waterreus, Anna, Webb, Bradley T., Weiser, Mark, Williams, Nigel M., Witt, Stephanie H., Wormley, Brandon K., Wu, Jing Qin, Xu, Zhida, Yolken, Robert, Zai, Clement C., Zhou, Wei, Zhu, Feng, Zimprich, Fritz, Atbaşoğlu, Eşref Cem, Ayub, Muhammad, Benner, Christian, Bertolino, Alessandro, Black, Donald W., Bray, Nicholas J., Breen, Gerome, Buccola, Nancy G., Byerley, William F., Chen, Wei J., Cloninger, C. Robert, Crespo-Facorro, Benedicto, Donohoe, Gary, Freedman, Robert, Galletly, Cherrie, Gandal, Michael J., Gennarelli, Massimo, Hougaard, David M., Hwu, Hai-Gwo, Jablensky, Assen V., McCarroll, Steven A., Moran, Jennifer L., Mors, Ole, Mortensen, Preben B., Müller-Myhsok, Bertram, Neil, Amanda L., Nordentoft, Merete, Pato, Michele T., Petryshen, Tracey L., Pirinen, Matti, Pulver, Ann E., Schulze, Thomas G., Silverman, Jeremy M., Smoller, Jordan W., Stahl, Eli A., Tsuang, Debby W., Vilella, Elisabet, Wang, Shi-Heng, Xu, Shuhua, Adolfsson, Rolf, Arango, Celso, Baune, Bernhard T., Belangero, Sintia Iole, Børglum, Anders D., Braff, David, Bramon, Elvira, Buxbaum, Joseph D., Campion, Dominique, Cervilla, Jorge A., Cichon, Sven, Collier, David A., Corvin, Aiden, Curtis, David, Forti, Marta Di, Domenici, Enrico, Ehrenreich, Hannelore, Escott-Price, Valentina, Esko, Tõnu, Fanous, Ayman H., Gareeva, Anna, Gawlik, Micha, Gejman, Pablo V., Gill, Michael, Glatt, Stephen J., Golimbet, Vera, Hong, Kyung Sue, Hultman, Christina M., Hyman, Steven E., Iwata, Nakao, Jönsson, Erik G., Kahn, René S., Kennedy, James L., Khusnutdinova, Elza, Kirov, George, Knowles, James A., Krebs, Marie-Odile, Laurent-Levinson, Claudine, Lee, Jimmy, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., Malhotra, Dheeraj, McIntosh, Andrew, McQuillin, Andrew, Menezes, Paulo R., Morgan, Vera A., Morris, Derek W., Mowry, Bryan J., Murray, Robin M., Nimgaonkar, Vishwajit, Nöthen, Markus M., Ophoff, Roel A., Paciga, Sara A., Palotie, Aarno, Pato, Carlos N., Qin, Shengying, Rietschel, Marcella, Riley, Brien P., Rivera, Margarita, Rujescu, Dan, Saka, Meram C., Sanders, Alan R., Schwab, Sibylle G., Serretti, Alessandro, Sham, Pak C., Shi, Yongyong, St Clair, David, Stefánsson, Hreinn, Stefansson, Kari, Tsuang, Ming T., van Os, Jim, Vawter, Marquis P., Weinberger, Daniel R., Werge, Thomas, Wildenauer, Dieter B., Yu, Xin, Yue, Weihua, Holmans, Peter A., Pocklington, Andrew J., Roussos, Panos, Vassos, Evangelos, Verhage, Matthijs, Visscher, Peter M., Yang, Jian, Posthuma, Danielle, Andreassen, Ole A., Kendler, Kenneth S., Owen, Michael J., Wray, Naomi R., Daly, Mark J., Huang, Hailiang, Neale, Benjamin M., Sullivan, Patrick F., Ripke, Stephan, Walters, James T. R., and O’Donovan, Michael C.

Published
2022
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15. Population-Based Risk of Psychiatric Disorders Associated With Recurrent Copy Number Variants.

Author

Vaez, Morteza, Montalbano, Simone, Calle Sánchez, Xabier, Georgii Hellberg, Kajsa-Lotta, Dehkordi, Saeid Rasekhi, Krebs, Morten Dybdahl, Meijsen, Joeri, Shorter, John, Bybjerg-Grauholm, Jonas, Mortensen, Preben B., Børglum, Anders D., Hougaard, David M., Nordentoft, Merete, Geschwind, Daniel H., Buil, Alfonso, Schork, Andrew J., Helenius, Dorte, Raznahan, Armin, Thompson, Wesley K., and Werge, Thomas

Subjects
DNA copy number variations, PROPORTIONAL hazards models, SCHIZOPHRENIA, MENTAL illness, GENERALIZED estimating equations
Abstract

This genetic association study assesses data from a case-cohort sample of individuals born in Denmark to provide population-based estimates of prevalence and risk associated with psychiatric disorders for recurrent copy number variants. Key Points: Question: What is the population-based prevalence and psychiatric risk associated with recurrent copy number variants (rCNVs) and how do they differ across outcomes and rCNVs? Findings: In a genetic association study of the Danish population born in 1981-2008 and followed up until 2015, most rCNV risk profiles were similar across autism, attention-deficit/hyperactivity disorder, and schizophrenia. The magnitude of risk increase correlated with locus size and gene constraint but did not differ between deletions and duplications. Meaning: Several rCNVs were more prevalent and conferred less risk of psychiatric disorders than estimated previously, which highlights the importance of population-based estimates for implementing genetics-based prediction in health care. Importance: Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is unknown. Objective: To provide unbiased population-based estimates of prevalence and risk associated with psychiatric disorders for rCNVs and to compare risks across outcomes, rCNV dosage type (deletions or duplications), and locus features. Design, Setting, and Participants: This genetic association study is an analysis of data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) case-cohort sample of individuals born in Denmark in 1981-2008 and followed up until 2015, including (1) all individuals (n = 92 531) with a hospital discharge diagnosis of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, major depressive disorder (MDD), or schizophrenia spectrum disorder (SSD) and (2) a subcohort (n = 50 625) randomly drawn from the source population. Data were analyzed from January 2021 to August 2023. Exposures: Carrier status of deletions and duplications at 27 autosomal rCNV loci was determined from neonatal blood samples genotyped on single-nucleotide variant microarrays. Main Outcomes and Measures: Population-based rCNV prevalence was estimated with a survey model using finite population correction to account for oversampling of cases. Hazard ratio (HR) estimates and 95% CIs for psychiatric disorders were derived using weighted Cox proportional hazard models. Risks were compared across outcomes, dosage type, and locus features using generalized estimating equation models. Results: A total of 3547 rCNVs were identified in 64 735 individuals assigned male at birth (53.8%) and 55 512 individuals assigned female at birth (46.2%) whose age at the end of follow-up ranged from 7.0 to 34.7 years (mean, 21.8 years). Most observed increases in rCNV-associated risk for ADHD, ASD, or SSD were moderate, and risk estimates were highly correlated across these disorders. Notable exceptions included high ASD-associated risk observed for Prader-Willi/Angelman syndrome duplications (HR, 20.8; 95% CI, 7.9-55). No rCNV was associated with increased MDD risk. Also, rCNV-associated risk was positively correlated with locus size and gene constraint but not with dosage type. Comparison with published case-control and community-based studies revealed a higher prevalence of deletions and lower associated increase in risk for several rCNVs in iPSYCH2015. Conclusions and Relevance: This study found that several rCNVs were more prevalent and conferred less risk of psychiatric disorders than estimated previously. Most case-control studies overestimate rCNV-associated risk of psychiatric disorders, likely because of selection bias. In an era where genetics is increasingly being clinically applied, these results highlight the importance of population-based risk estimates for genetics-based predictions. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study

Author

Wimberley, Theresa, primary, Brikell, Isabell, additional, Astrup, Aske, additional, Larsen, Janne T., additional, Petersen, Liselotte V., additional, Albiñana, Clara, additional, Vilhjálmsson, Bjarni J., additional, Bulik, Cynthia M., additional, Chang, Zheng, additional, Fanelli, Giuseppe, additional, Bralten, Janita, additional, Mota, Nina R., additional, Salas-Salvadó, Jordi, additional, Fernandez-Aranda, Fernando, additional, Bulló, Monica, additional, Franke, Barbara, additional, Børglum, Anders, additional, Mortensen, Preben B., additional, Horsdal, Henriette T., additional, and Dalsgaard, Søren, additional

Published
2024
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19. An epigenetic clock for gestational age at birth based on blood methylation data

Author

Knight, Anna K, Craig, Jeffrey M, Theda, Christiane, Bækvad-Hansen, Marie, Bybjerg-Grauholm, Jonas, Hansen, Christine S, Hollegaard, Mads V, Hougaard, David M, Mortensen, Preben B, Weinsheimer, Shantel M, Werge, Thomas M, Brennan, Patricia A, Cubells, Joseph F, Newport, D Jeffrey, Stowe, Zachary N, Cheong, Jeanie LY, Dalach, Philippa, Doyle, Lex W, Loke, Yuk J, Baccarelli, Andrea A, Just, Allan C, Wright, Robert O, Téllez-Rojo, Mara M, Svensson, Katherine, Trevisi, Letizia, Kennedy, Elizabeth M, Binder, Elisabeth B, Iurato, Stella, Czamara, Darina, Räikkönen, Katri, Lahti, Jari MT, Pesonen, Anu-Katriina, Kajantie, Eero, Villa, Pia M, Laivuori, Hannele, Hämäläinen, Esa, Park, Hea Jin, Bailey, Lynn B, Parets, Sasha E, Kilaru, Varun, Menon, Ramkumar, Horvath, Steve, Bush, Nicole R, LeWinn, Kaja Z, Tylavsky, Frances A, Conneely, Karen N, and Smith, Alicia K

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Infant Mortality, Clinical Research, Preterm, Low Birth Weight and Health of the Newborn, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Reproductive health and childbirth, Generic health relevance, Adult, Aging, Biomarkers, Birth Weight, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Fetal Development, Gestational Age, Humans, Infant, Newborn, Male, Pregnancy, Developmental age, Epigenetic clock, DNA methylation, Preterm birth, Cord blood, Fetus, Blood spot, Biomarker, Medicaid, Socioeconomic status, Birthweight, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundGestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth.ResultsWe find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry.ConclusionsDNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.

Published
2016

21. Potential causal association between gut microbiome and posttraumatic stress disorder

Author

Cardiologie, Onderzoeksgroep 2, Brain, MGGZ, Hersenen-Medisch 1, Neurogenetica, Diagnostiek & Vroege Psychose Medisch, He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., Provost, Allison C., Ratanatharathorn, Andrew, Stein, Murray B., Torres, Katy, Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Søren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Børglum, Anders D., Bradley, Bekh, Brashear, Megan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, José M., Dale, Anders M., Daly, Mark J., Daskalakis, Nikolaos P., Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Dzubur-Kulenovic, Alma, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue Jun, Junglen, Angela G., Karstoft, Karen Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin E., Linnstaedt, Sarah D., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica, Marmar, Charles, Martin, Alicia R., Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., McLeay, Sarah, Mehta, Divya, Milberg, William P., Miller, Mark W., Morey, Rajendra A., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben B., Neale, Benjamin M., Nelson, Elliot C., Nordentoft, Merete, Norman, Sonya B., O’Donnell, Meaghan, Orcutt, Holly K., Panizzon, Matthew S., Peters, Edward S., Peterson, Alan L., Peverill, Matthew, Pietrzak, Robert H., Polusny, Melissa A., Rice, John P., Ripke, Stephan, Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Ken, Rung, Ariane, Rutten, Bart P.F., Saccone, Nancy L., Sanchez, Sixto E., Schijven, Dick, Seedat, Soraya, Seligowski, Antonia V., Seng, Julia S., Sheerin, Christina M., Silove, Derrick, Smith, Alicia K., Smoller, Jordan W., Solovieff, Nadia, Sponheim, Scott R., Stein, Dan J., Sumner, Jennifer A., Teicher, Martin H., Thompson, Wesley K., Trapido, Edward, Uddin, Monica, Ursano, Robert J., van den Heuvel, Leigh Luella, van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan H., Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Wolff, Jonathan D., Yehuda, Rachel, Young, Keith A., Young, Ross Mc D., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, Koenen, Karestan C., Cardiologie, Onderzoeksgroep 2, Brain, MGGZ, Hersenen-Medisch 1, Neurogenetica, Diagnostiek & Vroege Psychose Medisch, He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., Provost, Allison C., Ratanatharathorn, Andrew, Stein, Murray B., Torres, Katy, Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Søren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Børglum, Anders D., Bradley, Bekh, Brashear, Megan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, José M., Dale, Anders M., Daly, Mark J., Daskalakis, Nikolaos P., Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Dzubur-Kulenovic, Alma, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue Jun, Junglen, Angela G., Karstoft, Karen Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin E., Linnstaedt, Sarah D., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica, Marmar, Charles, Martin, Alicia R., Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., McLeay, Sarah, Mehta, Divya, Milberg, William P., Miller, Mark W., Morey, Rajendra A., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben B., Neale, Benjamin M., Nelson, Elliot C., Nordentoft, Merete, Norman, Sonya B., O’Donnell, Meaghan, Orcutt, Holly K., Panizzon, Matthew S., Peters, Edward S., Peterson, Alan L., Peverill, Matthew, Pietrzak, Robert H., Polusny, Melissa A., Rice, John P., Ripke, Stephan, Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Ken, Rung, Ariane, Rutten, Bart P.F., Saccone, Nancy L., Sanchez, Sixto E., Schijven, Dick, Seedat, Soraya, Seligowski, Antonia V., Seng, Julia S., Sheerin, Christina M., Silove, Derrick, Smith, Alicia K., Smoller, Jordan W., Solovieff, Nadia, Sponheim, Scott R., Stein, Dan J., Sumner, Jennifer A., Teicher, Martin H., Thompson, Wesley K., Trapido, Edward, Uddin, Monica, Ursano, Robert J., van den Heuvel, Leigh Luella, van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan H., Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Wolff, Jonathan D., Yehuda, Rachel, Young, Keith A., Young, Ross Mc D., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, and Koenen, Karestan C.

Published
2024

22. A large-scale genome-wide association study meta-analysis of cannabis use disorder

Author

Walters, Raymond, Polimanti, Renato, Johnson, Emma, McClintick, Jeanette, Hatoum, Alexander, He, June, Wendt, Frank, Zhou, Hang, Adams, Mark, Adkins, Amy, Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna, Bigdeli, Tim, Chen, Li-Shiun, Clarke, Toni-Kim, Chou, Yi-Ling, Degenhardt, Franziska, Docherty, Anna, Edwards, Alexis, Fontanillas, Pierre, Foo, Jerome, Fox, Louis, Frank, Josef, Giegling, Ina, Gordon, Scott, Hack, Laura, Hartmann, Annette, Hartz, Sarah, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hodgkinson, Colin, Hoffman, Per, Hottenga, Jouke, Kennedy, Martin, Alanne-Kinnunen, Mervi, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion, Mbarek, Hamdi, McIntosh, Andrew, McQueen, Matthew, Meyers, Jacquelyn, Milaneschi, Yuri, Palviainen, Teemu, Pearson, John, Peterson, Roseann, Ripatti, Samuli, Ryu, Euijung, Saccone, Nancy, Salvatore, Jessica, Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen-Chyong, Webb, Bradley, Wedow, Robbee, Wetherill, Leah, Wills, Amanda, Boardman, Jason, Chen, Danfeng, Choi, Doo-Sup, Copeland, William, Culverhouse, Robert, Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin, Elson, Sarah, Frye, Mark, Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael, Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison, Nurnberger, John, Palotie, Aarno, Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen, Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc, Soyka, Michael, Treutlein, Jens, Witt, Stephanie, Wodarz, Norbert, Zill, Peter, Adkins, Daniel, Boden, Joseph, Boomsma, Dorret, Bierut, Laura, Brown, Sandra, Bucholz, Kathleen, Cichon, Sven, Costello, E. Jane, de Wit, Harriet, Diazgranados, Nancy, Dick, Danielle, Eriksson, Johan, Farrer, Lindsay, Foroud, Tatiana, Gillespie, Nathan, Goate, Alison, Goldman, David, Grucza, Richard, Hancock, Dana, Harris, Kathleen Mullan, Heath, Andrew, Hesselbrock, Victor, Hewitt, John, Hopfer, Christian, Horwood, John, Iacono, William, Johnson, Eric, Kaprio, Jaakko, Karpyak, Victor, Kendler, Kenneth, Kranzler, Henry, Krauter, Kenneth, Lichtenstein, Paul, Lind, Penelope, McGue, Matt, MacKillop, James, Madden, Pamela, Maes, Hermine, Magnusson, Patrik, Martin, Nicholas, Medland, Sarah, Montgomery, Grant, Nelson, Elliot, Nöthen, Markus, Palmer, Abraham, Pederson, Nancy, Penninx, Brenda, Porjesz, Bernice, Rice, John, Rietschel, Marcella, Riley, Brien, Rose, Richard, Rujescu, Dan, Shen, Pei-Hong, Silberg, Judy, Stallings, Michael, Tarter, Ralph, Vanyukov, Michael, Vrieze, Scott, Wall, Tamara, Whitfield, John, Zhao, Hongyu, Neale, Benjamin, Gelernter, Joel, Edenberg, Howard, Agrawal, Arpana, Johnson, Emma C, Demontis, Ditte, Thorgeirsson, Thorgeir E, Walters, Raymond K, Hatoum, Alexander S, Paul, Sarah E, Wendt, Frank R, Reginsson, Gunnar W, Baranger, David A A, Gudbjartsson, Daniel F, Adkins, Daniel E, Adkins, Amy E, Alexander, Jeffry, Bigdeli, Tim B, Brown, Sandra A, Bucholz, Kathleen K, Bybjerg-Grauholm, Jonas, Corley, Robin P, Dick, Danielle M, Domingue, Benjamin W, Goate, Alison M, Gordon, Scott D, Hack, Laura M, Hancock, Dana B, Hartz, Sarah M, Hickie, Ian B, Hougaard, David M, Lind, Penelope A, McClintick, Jeanette N, McQueen, Matthew B, Meyers, Jacquelyn L, Montgomery, Grant W, Mors, Ole, Mortensen, Preben B, Nordentoft, Merete, Pearson, John F, Peterson, Roseann E, Reynolds, Maureen D, Rice, John P, Runarsdottir, Valgerdur, Saccone, Nancy L, Silberg, Judy L, Tarter, Ralph E, Tyrfingsson, Thorarinn, Wall, Tamara L, Webb, Bradley T, Werge, Thomas, Wright, Margaret J, Zellers, Stephanie, Adams, Mark J, Bierut, Laura J, Boardman, Jason D, Copeland, William E, Farrer, Lindsay A, Foroud, Tatiana M, Gillespie, Nathan A, Grucza, Richard A, Heath, Andrew C, Hewitt, John K, Hopfer, Christian J, Iacono, William G, Johnson, Eric O, Kendler, Kenneth S, Kennedy, Martin A, Kranzler, Henry R, Madden, Pamela A F, Maes, Hermine H, Maher, Brion S, Martin, Nicholas G, McGue, Matthew, McIntosh, Andrew M, Medland, Sarah E, Nelson, Elliot C, Riley, Brien P, Stallings, Michael C, Vanyukov, Michael M, Davis, Lea K, Bogdan, Ryan, Edenberg, Howard J, Stefansson, Kari, and Børglum, Anders D

Published
2020
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23. Interplay of polygenic liability with birth-related, somatic, and psychosocial factors in anorexia nervosa risk: a nationwide study.

Author

Papini, Natalie M., Presseller, Emily, Bulik, Cynthia M., Holde, Katrine, Larsen, Janne T., Thornton, Laura M., Albiñana, Clara, Vilhjálmsson, Bjarni J., Mortensen, Preben B., Yilmaz, Zeynep, and Petersen, Liselotte V.

Subjects
RISK assessment, URINARY tract infections, CESAREAN section, RESEARCH funding, MATERNAL age, SOCIOECONOMIC factors, SEX distribution, MENTAL illness, REPORTING of diseases, AGE distribution, DESCRIPTIVE statistics, GENETIC risk score, ANOREXIA nervosa, DISEASE susceptibility, GENETICS
Abstract

Background: Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated. Methods: Participants were individuals born in Denmark between 1981 and 2008 including nationwide-representative data from the iPSYCH2015, and Danish AN cases from the Anorexia Nervosa Genetics Initiative and Eating Disorder Genetics Initiative cohorts. A total of 7003 individuals with AN and 45 229 individuals without a registered AN diagnosis were included. We included 22 AN risk factors from Danish registers. Results: Risk factors showing association with PRS for AN included urbanicity, parental ages, genitourinary tract infection, and parental socioeconomic factors. Risk factors showed the expected association to AN risk, and this association was only slightly attenuated when adjusted for parental history of psychiatric disorders or/and for the AN PRS. The interaction analyses revealed a differential effect of AN PRS according to the level of the following risk factors: sex, maternal age, genitourinary tract infection, C-section, parental socioeconomic factors and psychiatric history. Conclusions: Our findings provide evidence for interactions between AN PRS and certain risk-factors, illustrating potential diverse risk pathways to AN diagnosis. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Host–parasite interaction associated with major mental illness

Author

Kano, Shin-ichi, Hodgkinson, Colin A., Jones-Brando, Lorraine, Eastwood, Sharon, Ishizuka, Koko, Niwa, Minae, Choi, Eric Y., Chang, Daniel J., Chen, Yian, Velivela, Swetha D., Leister, Flora, Wood, Joel, Chowdari, Kodavali, Ducci, Francesca, Caycedo, Daniel A., Heinz, Elizabeth, Newman, Emily R., Cascella, Nicola, Mortensen, Preben B., Zandi, Peter P., Dickerson, Faith, Nimgaonkar, Vishwajit, Goldman, David, Harrison, Paul J., Yolken, Robert H., and Sawa, Akira

Published
2020
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32. Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia

Author

Forstner, Andreas J, Basmanav, F Buket, Mattheisen, Manuel, Investigators, Böhmer, Anne C, Hollegaard, Mads V, Janson, Esther, Strengman, Eric, Priebe, Lutz, Degenhardt, Franziska, Hoffmann, Per, Herms, Stefan, Maier, Wolfgang, Mössner, Rainald, Rujescu, Dan, Ophoff, Roel A, Moebus, Susanne, Mortensen, Preben B, Børglum, Anders D, Hougaard, David M, Frank, Josef, Witt, Stephanie H, Rietschel, Marcella, Zimmer, Andreas, Nöthen, Markus M, Miró, Xavier, and Cichon, Sven

Subjects
Serious Mental Illness, Schizophrenia, Human Genome, Neurosciences, Brain Disorders, Genetics, Mental Health, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Mental health, Acetyltransferases, Animals, Brain, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, Heterocyclic Compounds, Humans, In Situ Hybridization, Mice, Inbred C57BL, MicroRNAs, Microtubule Proteins, Receptor, trkC, White People, Clinical Sciences, Cognitive Sciences, Psychiatry
Abstract

BackgroundSchizophrenia is a complex neuropsychiatric disorder of unclear etiology. The strongest known genetic risk factor is the 22q11.2 microdeletion. Research has yet to confirm which genes within the deletion region are implicated in schizophrenia. The minimal 1.5 megabase deletion contains MIR185, which encodes microRNA 185.MethodsWe determined miR-185 expression in embryonic and adult mouse brains. Common and rare variants at this locus were then investigated using a human genetics approach. First, we performed gene-based analyses for MIR185 common variants and target genes using Psychiatric Genomics Consortium genome-wide association data. Second, MIR185 was resequenced in German patients (n = 1000) and controls (n = 500). We followed up promising variants by genotyping an additional European sample (patients, n = 3598; controls, n = 4082).ResultsIn situ hybridization in mice revealed miR-185 expression in brain regions implicated in schizophrenia. Gene-based tests revealed association between common variants in 3 MIR185 target genes (ATAT1, SH3PXD2A, NTRK3) and schizophrenia. Further analyses in mice revealed overlapping expression patterns for these target genes and miR-185. Resequencing identified 2 rare patient-specific novel variants flanking MIR185. However, follow-up genotyping provided no further evidence of their involvement in schizophrenia.LimitationsPower to detect rare variant associations was limited.ConclusionHuman genetic analyses generated no evidence of the involvement of MIR185 in schizophrenia. However, the expression patterns of miR-185 and its target genes in mice, and the genetic association results for the 3 target genes, suggest that further research into the involvement of miR-185 and its downstream pathways in schizophrenia is warranted.

Published
2014

34. Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

Author

Ripke, Stephan, O'Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L, Kähler, Anna K, Akterin, Susanne, Bergen, Sarah E, Collins, Ann L, Crowley, James J, Fromer, Menachem, Kim, Yunjung, Lee, Sang Hong, Magnusson, Patrik KE, Sanchez, Nick, Stahl, Eli A, Williams, Stephanie, Wray, Naomi R, Xia, Kai, Bettella, Francesco, Borglum, Anders D, Bulik-Sullivan, Brendan K, Cormican, Paul, Craddock, Nick, de Leeuw, Christiaan, Durmishi, Naser, Gill, Michael, Golimbet, Vera, Hamshere, Marian L, Holmans, Peter, Hougaard, David M, Kendler, Kenneth S, Lin, Kuang, Morris, Derek W, Mors, Ole, Mortensen, Preben B, Neale, Benjamin M, O'Neill, Francis A, Owen, Michael J, Milovancevic, Milica Pejovic, Posthuma, Danielle, Powell, John, Richards, Alexander L, Riley, Brien P, Ruderfer, Douglas, Rujescu, Dan, Sigurdsson, Engilbert, Silagadze, Teimuraz, Smit, August B, Stefansson, Hreinn, Steinberg, Stacy, Suvisaari, Jaana, Tosato, Sarah, Verhage, Matthijs, Walters, James T, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson, Douglas F, Gejman, Pablo V, Laurent, Claudine, Mowry, Bryan J, O'Donovan, Michael C, Pulver, Ann E, Schwab, Sibylle G, Wildenauer, Dieter B, Dudbridge, Frank, Shi, Jianxin, Albus, Margot, Alexander, Madeline, Campion, Dominique, Cohen, David, Dikeos, Dimitris, Duan, Jubao, Eichhammer, Peter, Godard, Stephanie, Hansen, Mark, Lerer, F Bernard, Liang, Kung-Yee, Maier, Wolfgang, Mallet, Jacques, Nertney, Deborah A, Nestadt, Gerald, Norton, Nadine, Papadimitriou, George N, Ribble, Robert, Sanders, Alan R, Silverman, Jeremy M, Walsh, Dermot, Williams, Nigel M, Wormley, Brandon, Psychosis Endophenotypes International Consortium, Arranz, Maria J, Bakker, Steven, Bender, Stephan, Bramon, Elvira, and Collier, David

Subjects
Multicenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, Humans, Genetic Predisposition to Disease, Case-Control Studies, Schizophrenia, Polymorphism, Single Nucleotide, Sweden, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Published
2013

36. FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses

Author

Ahluwalia, Tarunveer S., Eliasen, Anders U., Sevelsted, Astrid, Pedersen, Casper-Emil T., Stokholm, Jakob, Chawes, Bo, Bork-Jensen, Jette, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Sharma, Amitabh, Weiss, Scott T., Evans, Michael D., Jackson, Daniel J., Morin, Andreanne, Krogfelt, Karen A., Schjørring, Susanne, Mortensen, Preben B., Hougaard, David M., Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Mors, Ole, Nordentoft, Merete, Børglum, Anders D., Werge, Thomas, Agerbo, Esben, Gern, James E., Lemanske, Jr., Robert F., Ober, Carole, Pedersen, Anders G., Bisgaard, Hans, and Bønnelykke, Klaus

Published
2020
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37. Risk of Depression in People With HIV: A nationwide population-based matched cohort study

Author

Vollmond, Cecilie V, primary, Tetens, Malte M, additional, Paulsen, Fie W, additional, Gerstoft, Jan, additional, Kronborg, Gitte, additional, Johansen, Isik S, additional, Larsen, Carsten S, additional, Wiese, Lothar, additional, Dalager-Pedersen, Michael, additional, Leth, Steffen, additional, Mortensen, Preben B, additional, Lebech, Anne-Mette, additional, Obel, Niels, additional, and Omland, Lars H, additional

Published
2023
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41. Risk of Depression in People With Human Immunodeficiency Virus: A Nationwide Population-based Matched Cohort Study.

Author

Vollmond, Cecilie V, Tetens, Malte M, Paulsen, Fie W, Gerstoft, Jan, Kronborg, Gitte, Johansen, Isik S, Larsen, Carsten S, Wiese, Lothar, Dalager-Pedersen, Michael, Leth, Steffen, Mortensen, Preben B, Lebech, Anne-Mette, Obel, Niels, and Omland, Lars H

Subjects
MENTAL depression risk factors, HIV-positive persons, CONFIDENCE intervals, RESEARCH funding, HUMAN beings, LONGITUDINAL method, PROPORTIONAL hazards models
Abstract

Background Human immunodeficiency virus (HIV) infection is associated with depression. However, previous studies have not addressed familial factors. Methods Nationwide, population-based, matched cohort study of people with HIV (PWH) in Denmark between 1995 and 2021 who were matched on sex and date of birth with a comparison cohort randomly selected from the Danish population. Family-related factors were examined by inclusion of siblings of those in the cohorts. We calculated hazard ratios (HRs) for depression, receipt of antidepressants, electroconvulsive therapy (ECT), and suicide, as well as the yearly proportions of study cohorts with psychiatric hospital contact due to depression and receipt of antidepressants from 10 years before to 10 years after study inclusion. Results We included 5943 PWH and 59 430 comparison cohort members. Median age was 38 years, and 25% were women. We observed an increased risk of depression, receipt of antidepressants, ECT, and suicide among PWH in the 2 first years of observation (HR, 3.3; 95% confidence interval [CI]: 2.5–4.4), HR, 3.0 (95% CI: 2.7–3.4), HR, 2.8 (95% CI:.9–8.6), and HR, 10.7 (95% CI: 5.2–22.2), thereafter the risk subsided but remained increased. The proportions of PWH with psychiatric hospital contact due to depression and receipt of antidepressants were increased prior to and especially after HIV diagnosis. Risk of all outcomes was substantially lower among siblings of PWH than among PWH (HR for receipt of antidepressants, 1.1; 95% CI: 1.0–1.2). Conclusions PWH have an increased risk of depression. Family-related factors are unlikely to explain this risk. [ABSTRACT FROM AUTHOR]

Published
2023
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44. ADuLT:An efficient and robust time-to-event GWAS

Author

Pedersen, Emil M., Agerbo, Esben, Plana-Ripoll, Oleguer, Steinbach, Jette, Krebs, Morten D., Hougaard, David M., Werge, Thomas, Nordentoft, Merete, Børglum, Anders D., Musliner, Katherine L., Ganna, Andrea, Schork, Andrew J., Mortensen, Preben B., McGrath, John J., Privé, Florian, Vilhjálmsson, Bjarni J., Pedersen, Emil M., Agerbo, Esben, Plana-Ripoll, Oleguer, Steinbach, Jette, Krebs, Morten D., Hougaard, David M., Werge, Thomas, Nordentoft, Merete, Børglum, Anders D., Musliner, Katherine L., Ganna, Andrea, Schork, Andrew J., Mortensen, Preben B., McGrath, John J., Privé, Florian, and Vilhjálmsson, Bjarni J.

Abstract

Proportional hazards models have been proposed to analyse time-to-event phenotypes in genome-wide association studies (GWAS). However, little is known about the ability of proportional hazards models to identify genetic associations under different generative models and when ascertainment is present. Here we propose the age-dependent liability threshold (ADuLT) model as an alternative to a Cox regression based GWAS, here represented by SPACox. We compare ADuLT, SPACox, and standard case-control GWAS in simulations under two generative models and with varying degrees of ascertainment as well as in the iPSYCH cohort. We find Cox regression GWAS to be underpowered when cases are strongly ascertained (cases are oversampled by a factor 5), regardless of the generative model used. ADuLT is robust to ascertainment in all simulated scenarios. Then, we analyse four psychiatric disorders in iPSYCH, ADHD, Autism, Depression, and Schizophrenia, with a strong case-ascertainment. Across these psychiatric disorders, ADuLT identifies 20 independent genome-wide significant associations, case-control GWAS finds 17, and SPACox finds 8, which is consistent with simulation results. As more genetic data are being linked to electronic health records, robust GWAS methods that can make use of age-of-onset information will help increase power in analyses for common health outcomes.

Published
2023

45. Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset:a case-cohort study

Author

Sánchez, Xabier Calle, Montalbano, Simone, Vaez, Morteza, Krebs, Morten Dybdahl, Byberg-Grauholm, Jonas, Mortensen, Preben B., Børglum, Anders D., Hougaard, David M., Nordentoft, Merete, Geschwind, Daniel H., Buil, Alfonso, Schork, Andrew J., Thompson, Wesley K., Raznahan, Armin, Helenius, Dorte, Werge, Thomas, Ingason, Andrés, Sánchez, Xabier Calle, Montalbano, Simone, Vaez, Morteza, Krebs, Morten Dybdahl, Byberg-Grauholm, Jonas, Mortensen, Preben B., Børglum, Anders D., Hougaard, David M., Nordentoft, Merete, Geschwind, Daniel H., Buil, Alfonso, Schork, Andrew J., Thompson, Wesley K., Raznahan, Armin, Helenius, Dorte, Werge, Thomas, and Ingason, Andrés

Abstract

Background: Increased prevalence of mental illness has been reported in clinical studies of sex chromosome aneuploidies, but accurate population-based estimates of the prevalence and clinical detection rate of sex chromosome aneuploidies and the associated risks of psychiatric disorders are needed. In this study, we provide such estimates, valid for children and young adults of the contemporary Danish population. Methods: We used the iPSYCH2015 case-cohort dataset, which is based on a source population of single-born individuals born in Denmark between May 1, 1981, and Dec 31, 2008. The case sample comprises all individuals from the source population with a diagnosis of any index psychiatric disorder (schizophrenia spectrum disorder, bipolar disorder, major depressive disorder, autism spectrum disorder, or ADHD) by the end of follow-up (Dec 31, 2015), registered in the hospital-based Danish Psychiatric Central Research Register. The cohort consists of individuals randomly selected from the source population, and overlaps with the case sample. Biobanked blood samples for individuals in the case and cohort samples underwent genotyping and quality-control filtering, after which we analysed microarray data to detect sex chromosome aneuploidy karyotypes (45,X, 47,XXX, 47,XXY, and 47,XYY). We estimated the population-valid prevalence of these karyotypes from the cohort sample. Weighted Cox proportional hazards models were used to estimate the risks of each index psychiatric disorder associated with each sex chromosome aneuploidy karyotype, by use of date of first hospitalisation with the index disorder in the respective case group and the cohort as outcome. The clinical detection rate was determined by comparing records of clinical diagnoses of genetic conditions from the Danish National Patient Register with sex chromosome aneuploidy karyotype determined by our study. Findings: The assessed sample comprised 119 481 individuals (78 726 in the case sample and 43 326 in

Published
2023

46. School performance and genetic propensities for educational attainment and depression in the etiology of self-harm:a Danish population-based study

Author

Sørensen, Holger J, Antonsen, Sussie, Benros, Michael E, Erlangsen, Annette, Albiñana, Clara, Nordentoft, Merete, Børglum, Anders D, Mors, Ole, Werge, Thomas, Mortensen, Preben B, Hougaard, David, Webb, Roger T, Agerbo, Esben, Sørensen, Holger J, Antonsen, Sussie, Benros, Michael E, Erlangsen, Annette, Albiñana, Clara, Nordentoft, Merete, Børglum, Anders D, Mors, Ole, Werge, Thomas, Mortensen, Preben B, Hougaard, David, Webb, Roger T, and Agerbo, Esben

Abstract

BACKGROUND: Poor school performance is linked to higher risks of self-harm. The association might be explained through genetic liabilities for depression or educational attainment. We investigated the association between school performance and self-harm in a population-based sample while assessing the potential influence of polygenic risk scores (PRSs) for depression (PRSMDD) and for educational attainment (PRSEDU).METHOD: We conducted a follow-up study of individuals born 1987-98 and followed from age 18 until 2016. The total sample consisted of a case group (23,779 diagnosed with mental disorders; schizophrenia, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder (ADHD) and a randomly sampled comparison group (n = 10,925). Genome-wide data were obtained from the Neonatal Screening Biobank and information on school performance, family psychiatric history, and socioeconomic status from national administrative registers.RESULTS: Individuals in the top PRSMDD decile were at higher self-harm risk in the case group (IRR: 1.30; 95% CI 1.15-1.46), whereas individuals in the top PRSEDU decile were at lower self-harm risk (IRR: 0.63; 95% CI: 0.55-0.74). Poorer school performance was associated with higher self-harm risk in persons diagnosed with any mental disorder (IRR: 1.69; 95% CI: 1.44-1.99) and among the comparison group (IRR: 7.93; 95% CI: 4.47-15.18). Observed effects of PRSMDD and PRSEDU on self-harm risk were strongest for individuals with poor school performance.CONCLUSION: Associations between PRSMDD and self-harm risk and between PRSEDU and self-harm risk were found. Nevertheless, these polygenic scores seem currently of limited clinical utility for identifying individuals at high self-harm risk.

Published
2023

47. Genome-wide by Environment Interaction Study of Stressful Life Events and Hospital-Treated Depression in the iPSYCH2012 Sample

Author

Suppli, Nis P., Andersen, Klaus K., Agerbo, Esben, Rajagopal, Veera M., Appadurai, Vivek, Coleman, Jonathan R.i., Breen, Gerome, Bybjerg-grauholm, Jonas, Bækvad-hansen, Marie, Pedersen, Carsten B., Pedersen, Marianne G., Thompson, Wesley K., Munk-Olsen, Trine, Benros, Michael E., Als, Thomas D., Grove, Jakob, Werge, Thomas, Børglum, Anders D., Hougaard, David M., Mors, Ole, Nordentoft, Merete, Mortensen, Preben B., Musliner, Katherine L., Suppli, Nis P., Andersen, Klaus K., Agerbo, Esben, Rajagopal, Veera M., Appadurai, Vivek, Coleman, Jonathan R.i., Breen, Gerome, Bybjerg-grauholm, Jonas, Bækvad-hansen, Marie, Pedersen, Carsten B., Pedersen, Marianne G., Thompson, Wesley K., Munk-Olsen, Trine, Benros, Michael E., Als, Thomas D., Grove, Jakob, Werge, Thomas, Børglum, Anders D., Hougaard, David M., Mors, Ole, Nordentoft, Merete, Mortensen, Preben B., and Musliner, Katherine L.

Abstract

Background Researchers have long investigated a hypothesized interaction between genetic risk and stressful life events in the etiology of depression, but studies on the topic have yielded inconsistent results. Methods We conducted a genome-wide by environment interaction study (GWEIS) in 18,532 patients with depression from hospital-based settings and 20,184 population controls. All individuals were drawn from the iPSYCH2012 case-cohort study, a nationally representative sample identified from Danish national registers. Information on stressful life events including family disruption, serious medical illness, death of a first-degree relative, parental disability, and child maltreatment was identified from the registers and operationalized as a time-varying count variable. Hazard ratios for main and interaction effects were estimated using Cox regressions weighted to accommodate the case-cohort design. Our replication sample included 22,880 depression cases and 50,378 controls from the UK Biobank. Results The GWEIS in the iPSYCH2012 sample yielded three novel, genome-wide–significant (p < 5 × 10−8) loci located in the ABCC1 gene (rs56076205, p = 3.7 × 10−10), the AKAP6 gene (rs3784187, p = 1.2 × 10−8), and near the MFSD1 gene (rs340315, p = 4.5 × 10−8). No hits replicated in the UK Biobank (rs56076205: p = .87; rs3784187: p = .93; rs340315: p = .71). Conclusions In this large, population-based GWEIS, we did not find any replicable hits for interaction. Future gene-by-stress research in depression should focus on establishing even larger collaborative GWEISs to attain sufficient power.

Published
2023

48. Risk of Depression in People With Human Immunodeficiency Virus:A Nationwide Population-based Matched Cohort Study

Author

Vollmond, Cecilie V., Tetens, Malte M., Paulsen, Fie W., Gerstoft, Jan, Kronborg, Gitte, Johansen, Isik S., Larsen, Carsten S., Wiese, Lothar, Dalager-Pedersen, Michael, Leth, Steffen, Mortensen, Preben B., Lebech, Anne Mette, Obel, Niels, Omland, Lars H., Vollmond, Cecilie V., Tetens, Malte M., Paulsen, Fie W., Gerstoft, Jan, Kronborg, Gitte, Johansen, Isik S., Larsen, Carsten S., Wiese, Lothar, Dalager-Pedersen, Michael, Leth, Steffen, Mortensen, Preben B., Lebech, Anne Mette, Obel, Niels, and Omland, Lars H.

Abstract

Background Human immunodeficiency virus (HIV) infection is associated with depression. However, previous studies have not addressed familial factors. Methods Nationwide, population-based, matched cohort study of people with HIV (PWH) in Denmark between 1995 and 2021 who were matched on sex and date of birth with a comparison cohort randomly selected from the Danish population. Family-related factors were examined by inclusion of siblings of those in the cohorts. We calculated hazard ratios (HRs) for depression, receipt of antidepressants, electroconvulsive therapy (ECT), and suicide, as well as the yearly proportions of study cohorts with psychiatric hospital contact due to depression and receipt of antidepressants from 10 years before to 10 years after study inclusion. Results We included 5943 PWH and 59 430 comparison cohort members. Median age was 38 years, and 25% were women. We observed an increased risk of depression, receipt of antidepressants, ECT, and suicide among PWH in the 2 first years of observation (HR, 3.3; 95% confidence interval [CI]: 2.5–4.4), HR, 3.0 (95% CI: 2.7–3.4), HR, 2.8 (95% CI: .9–8.6), and HR, 10.7 (95% CI: 5.2–22.2), thereafter the risk subsided but remained increased. The proportions of PWH with psychiatric hospital contact due to depression and receipt of antidepressants were increased prior to and especially after HIV diagnosis. Risk of all outcomes was substantially lower among siblings of PWH than among PWH (HR for receipt of antidepressants, 1.1; 95% CI: 1.0–1.2). Conclusions PWH have an increased risk of depression. Family-related factors are unlikely to explain this risk., Background: Human immunodeficiency virus (HIV) infection is associated with depression. However, previous studies have not addressed familial factors. Methods: Nationwide, population-based, matched cohort study of people with HIV (PWH) in Denmark between 1995 and 2021 who were matched on sex and date of birth with a comparison cohort randomly selected from the Danish population. Family-related factors were examined by inclusion of siblings of those in the cohorts. We calculated hazard ratios (HRs) for depression, receipt of antidepressants, electroconvulsive therapy (ECT), and suicide, as well as the yearly proportions of study cohorts with psychiatric hospital contact due to depression and receipt of antidepressants from 10 years before to 10 years after study inclusion. Results: We included 5943 PWH and 59 430 comparison cohort members. Median age was 38 years, and 25% were women. We observed an increased risk of depression, receipt of antidepressants, ECT, and suicide among PWH in the 2 first years of observation (HR, 3.3; 95% confidence interval [CI]: 2.5-4.4), HR, 3.0 (95% CI: 2.7-3.4), HR, 2.8 (95% CI:. 9-8.6), and HR, 10.7 (95% CI: 5.2-22.2), thereafter the risk subsided but remained increased. The proportions of PWH with psychiatric hospital contact due to depression and receipt of antidepressants were increased prior to and especially after HIV diagnosis. Risk of all outcomes was substantially lower among siblings of PWH than among PWH (HR for receipt of antidepressants, 1.1; 95% CI: 1.0-1.2). Conclusions: PWH have an increased risk of depression. Family-related factors are unlikely to explain this risk.

Published
2023

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