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49 results on '"Rajagopal, Veera M."'

1. A deep catalogue of protein-coding variation in 983,578 individuals

Author

Sun, Kathie Y., Bai, Xiaodong, Chen, Siying, Bao, Suying, Zhang, Chuanyi, Kapoor, Manav, Backman, Joshua, Joseph, Tyler, Maxwell, Evan, Mitra, George, Gorovits, Alexander, Mansfield, Adam, Boutkov, Boris, Gokhale, Sujit, Habegger, Lukas, Marcketta, Anthony, Locke, Adam E., Ganel, Liron, Hawes, Alicia, Kessler, Michael D., Sharma, Deepika, Staples, Jeffrey, Bovijn, Jonas, Gelfman, Sahar, Di Gioia, Alessandro, Rajagopal, Veera M., Lopez, Alexander, Varela, Jennifer Rico, Alegre-Díaz, Jesús, Berumen, Jaime, Tapia-Conyer, Roberto, Kuri-Morales, Pablo, Torres, Jason, Emberson, Jonathan, Collins, Rory, Cantor, Michael, Thornton, Timothy, Kang, Hyun Min, Overton, John D., Shuldiner, Alan R., Cremona, M. Laura, Nafde, Mona, Baras, Aris, Abecasis, Gonçalo, Marchini, Jonathan, Reid, Jeffrey G., Salerno, William, and Balasubramanian, Suganthi

Published
2024
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2. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications

Author

Levey, Daniel F., Galimberti, Marco, Deak, Joseph D., Wendt, Frank R., Bhattacharya, Arjun, Koller, Dora, Harrington, Kelly M., Quaden, Rachel, Johnson, Emma C., Gupta, Priya, Biradar, Mahantesh, Lam, Max, Cooke, Megan, Rajagopal, Veera M., Empke, Stefany L. L., Zhou, Hang, Nunez, Yaira Z., Kranzler, Henry R., Edenberg, Howard J., Agrawal, Arpana, Smoller, Jordan W., Lencz, Todd, Hougaard, David M., Børglum, Anders D., Demontis, Ditte, Gaziano, J. Michael, Gandal, Michael J., Polimanti, Renato, Stein, Murray B., and Gelernter, Joel

Published
2023
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3. Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci

Author

Deak, Joseph D, Zhou, Hang, Galimberti, Marco, Levey, Daniel F, Wendt, Frank R, Sanchez-Roige, Sandra, Hatoum, Alexander S, Johnson, Emma C, Nunez, Yaira Z, Demontis, Ditte, Børglum, Anders D, Rajagopal, Veera M, Jennings, Mariela V, Kember, Rachel L, Justice, Amy C, Edenberg, Howard J, Agrawal, Arpana, Polimanti, Renato, Kranzler, Henry R, and Gelernter, Joel

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Genetics, Substance Misuse, Brain Disorders, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Humans, Alcoholism, Furin, Genetic Predisposition to Disease, Genome-Wide Association Study, Opioid-Related Disorders, Phenotype, Polymorphism, Single Nucleotide, Black People, White People, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Despite the large toll of opioid use disorder (OUD), genome-wide association studies (GWAS) of OUD to date have yielded few susceptibility loci. We performed a large-scale GWAS of OUD in individuals of European (EUR) and African (AFR) ancestry, optimizing genetic informativeness by performing MTAG (Multi-trait analysis of GWAS) with genetically correlated substance use disorders (SUDs). Meta-analysis included seven cohorts: the Million Veteran Program, Psychiatric Genomics Consortium, iPSYCH, FinnGen, Partners Biobank, BioVU, and Yale-Penn 3, resulting in a total N = 639,063 (Ncases = 20,686;Neffective = 77,026) across ancestries. OUD cases were defined as having a lifetime OUD diagnosis, and controls as anyone not known to meet OUD criteria. We estimated SNP-heritability (h2SNP) and genetic correlations (rg). Based on genetic correlation, we performed MTAG on OUD, alcohol use disorder (AUD), and cannabis use disorder (CanUD). A leave-one-out polygenic risk score (PRS) analysis was performed to compare OUD and OUD-MTAG PRS as predictors of OUD case status in Yale-Penn 3. The EUR meta-analysis identified three genome-wide significant (GWS; p ≤ 5 × 10-8) lead SNPs-one at FURIN (rs11372849; p = 9.54 × 10-10) and two OPRM1 variants (rs1799971, p = 4.92 × 10-09; rs79704991, p = 1.11 × 10-08; r2 = 0.02). Rs1799971 (p = 4.91 × 10-08) and another OPRM1 variant (rs9478500; p = 1.95 × 10-08; r2 = 0.03) were identified in the cross-ancestry meta-analysis. Estimated h2SNP was 12.75%, with strong rg with CanUD (rg = 0.82; p = 1.14 × 10-47) and AUD (rg = 0.77; p = 6.36 × 10-78). The OUD-MTAG resulted in a GWAS Nequivalent = 128,748 and 18 independent GWS loci, some mapping to genes or gene regions that have previously been associated with psychiatric or addiction phenotypes. The OUD-MTAG PRS accounted for 3.81% of OUD variance (beta = 0.61;s.e. = 0.066; p = 2.00 × 10-16) compared to 2.41% (beta = 0.45; s.e. = 0.058; p = 2.90 × 10-13) explained by the OUD PRS. The current study identified OUD variant associations at OPRM1, single variant associations with FURIN, and 18 GWS associations in the OUD-MTAG. The genetic architecture of OUD is likely influenced by both OUD-specific loci and loci shared across SUDs.

Published
2022

4. 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

5. Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity

Author

Rajagopal, Veera M., Ganna, Andrea, Coleman, Jonathan R. I., Allegrini, Andrea, Voloudakis, Georgios, Grove, Jakob, Als, Thomas D., Horsdal, Henriette T., Petersen, Liselotte, Appadurai, Vivek, Schork, Andrew, Buil, Alfonso, Bulik, Cynthia M., Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Hougaard, David M., Mors, Ole, Nordentoft, Merete, Werge, Thomas, Mortensen, Preben Bo, Breen, Gerome, Roussos, Panos, Plomin, Robert, Agerbo, Esben, Børglum, Anders D., and Demontis, Ditte

Published
2023
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6. 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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7. Rare coding variants in CHRNB2 reduce the likelihood of smoking

Author

Rajagopal, Veera M., Watanabe, Kyoko, Mbatchou, Joelle, Ayer, Ariane, Quon, Peter, Sharma, Deepika, Kessler, Michael D., Praveen, Kavita, Gelfman, Sahar, Parikshak, Neelroop, Otto, Jacqueline M., Bao, Suying, Chim, Shek Man, Pavlopoulos, Elias, Avbersek, Andreja, Kapoor, Manav, Chen, Esteban, Jones, Marcus B., Leblanc, Michelle, Emberson, Jonathan, Collins, Rory, Torres, Jason, Morales, Pablo Kuri, Tapia-Conyer, Roberto, Alegre, Jesus, Berumen, Jaime, Shuldiner, Alan R., Balasubramanian, Suganthi, Abecasis, Gonçalo R., Kang, Hyun M., Marchini, Jonathan, Stahl, Eli A., Jorgenson, Eric, Sanchez, Robert, Liedtke, Wolfgang, Anderson, Matthew, Cantor, Michael, Lederer, David, Baras, Aris, and Coppola, Giovanni

Published
2023
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8. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder.

Author

Demontis, Ditte, Walters, Raymond K, Rajagopal, Veera M, Waldman, Irwin D, Grove, Jakob, Als, Thomas D, Dalsgaard, Søren, Ribasés, Marta, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Maria, Werge, Thomas, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Cormand, Bru, Hougaard, David M, Neale, Benjamin M, Franke, Barbara, Faraone, Stephen V, and Børglum, Anders D

Subjects
ADHD Working Group of the Psychiatric Genomics Consortium, Humans, Genetic Predisposition to Disease, Risk Factors, Cohort Studies, Attention Deficit and Disruptive Behavior Disorders, Attention Deficit Disorder with Hyperactivity, Comorbidity, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Child, China, Europe, Female, Male, Genome-Wide Association Study, Violence Research, Prevention, Pediatric, Genetics, Attention Deficit Disorder (ADD), Brain Disorders, Mental Health, Human Genome, Behavioral and Social Science, 2.1 Biological and endogenous factors, Mental health
Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10-10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.

Published
2021

9. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

Author

Demontis, Ditte, Walters, G. Bragi, Athanasiadis, Georgios, Walters, Raymond, Therrien, Karen, Nielsen, Trine Tollerup, Farajzadeh, Leila, Voloudakis, Georgios, Bendl, Jaroslav, Zeng, Biau, Zhang, Wen, Grove, Jakob, Als, Thomas D., Duan, Jinjie, Satterstrom, F. Kyle, Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Gudmundsson, Olafur O., Magnusson, Sigurdur H., Baldursson, Gisli, Davidsdottir, Katrin, Haraldsdottir, Gyda S., Agerbo, Esben, Hoffman, Gabriel E., Dalsgaard, Søren, Martin, Joanna, Ribasés, Marta, Boomsma, Dorret I., Soler Artigas, Maria, Roth Mota, Nina, Howrigan, Daniel, Medland, Sarah E., Zayats, Tetyana, Rajagopal, Veera M., Nordentoft, Merete, Mors, Ole, Hougaard, David M., Mortensen, Preben Bo, Daly, Mark J., Faraone, Stephen V., Stefansson, Hreinn, Roussos, Panos, Franke, Barbara, Werge, Thomas, Neale, Benjamin M., Stefansson, Kari, and Børglum, Anders D.

Published
2023
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10. Common and rare variant associations with clonal haematopoiesis phenotypes

Author

Kessler, Michael D., Damask, Amy, O’Keeffe, Sean, Banerjee, Nilanjana, Li, Dadong, Watanabe, Kyoko, Marketta, Anthony, Van Meter, Michael, Semrau, Stefan, Horowitz, Julie, Tang, Jing, Kosmicki, Jack A., Rajagopal, Veera M., Zou, Yuxin, Houvras, Yariv, Ghosh, Arkopravo, Gillies, Christopher, Mbatchou, Joelle, White, Ryan R., Verweij, Niek, Bovijn, Jonas, Parikshak, Neelroop N., LeBlanc, Michelle G., Jones, Marcus, Glass, David J., Lotta, Luca A., Cantor, Michael N., Atwal, Gurinder S., Locke, Adam E., Ferreira, Manuel A. R., Deering, Raquel, Paulding, Charles, Shuldiner, Alan R., Thurston, Gavin, Ferrando, Adolfo A., Salerno, Will, Reid, Jeffrey G., Overton, John D., Marchini, Jonathan, Kang, Hyun M., Baras, Aris, Abecasis, Gonçalo R., and Jorgenson, Eric

Published
2022
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11. 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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12. Publisher Correction: Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Author

Huckins, Laura M, Dobbyn, Amanda, Ruderfer, Douglas M, Hoffman, Gabriel, Wang, Weiqing, Pardiñas, Antonio F, Rajagopal, Veera M, Als, Thomas D, T. Nguyen, Hoang, Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R, Purcell, Shaun, Demontis, Ditte, Børglum, Anders D, Walters, James TR, O’Donovan, Michael C, Sullivan, Patrick, Owen, Michael J, Devlin, Bernie, Sieberts, Solveig K, Cox, Nancy J, Im, Hae Kyung, Sklar, Pamela, and Stahl, Eli A

Subjects
Genetics, Neurosciences, Human Genome, Serious Mental Illness, Schizophrenia, Brain Disorders, Mental Health, Biotechnology, Mental health, CommonMind Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, iPSYCH-GEMS Schizophrenia Working Group, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

In the HTML version of the article originally published, the author group 'The Schizophrenia Working Group of the Psychiatric Genomics Consortium' was displayed incorrectly. The error has been corrected in the HTML version of the article.

Published
2019

13. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Author

Huckins, Laura M, Dobbyn, Amanda, Ruderfer, Douglas M, Hoffman, Gabriel, Wang, Weiqing, Pardiñas, Antonio F, Rajagopal, Veera M, Als, Thomas D, T. Nguyen, Hoang, Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R, Purcell, Shaun, Demontis, Ditte, Børglum, Anders D, Walters, James TR, O’Donovan, Michael C, Sullivan, Patrick, Owen, Michael J, Devlin, Bernie, Sieberts, Solveig K, Cox, Nancy J, Im, Hae Kyung, Sklar, Pamela, and Stahl, Eli A

Subjects
Biological Sciences, Genetics, Mental Health, Brain Disorders, Human Genome, Schizophrenia, 2.1 Biological and endogenous factors, Aetiology, Mental health, Brain, Case-Control Studies, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk, Transcriptome, CommonMind Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, iPSYCH-GEMS Schizophrenia Working Group, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

Published
2019

14. Author Correction: Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

Author

Demontis, Ditte, Walters, G. Bragi, Athanasiadis, Georgios, Walters, Raymond, Therrien, Karen, Nielsen, Trine Tollerup, Farajzadeh, Leila, Voloudakis, Georgios, Bendl, Jaroslav, Zeng, Biau, Zhang, Wen, Grove, Jakob, Als, Thomas D., Duan, Jinjie, Satterstrom, F. Kyle, Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Gudmundsson, Olafur O., Magnusson, Sigurdur H., Baldursson, Gisli, Davidsdottir, Katrin, Haraldsdottir, Gyda S., Agerbo, Esben, Hoffman, Gabriel E., Dalsgaard, Søren, Martin, Jonna, Ribasés, Marta, Boomsma, Dorret I., Soler Artigas, Maria, Roth Mota, Nina, Howrigan, Daniel, Medland, Sarah E., Zayats, Tetyana, Rajagopal, Veera M., Nordentoft, Merete, Mors, Ole, Hougaard, David M., Mortensen, Preben Bo, Daly, Mark J., Faraone, Stephen V., Stefansson, Hreinn, Roussos, Panos, Franke, Barbara, Werge, Thomas, Neale, Benjamin M., Stefansson, Kari, and Børglum, Anders D.

Published
2023
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15. Author Correction: Common and rare variant associations with clonal haematopoiesis phenotypes

Author

Kessler, Michael D., Damask, Amy, O’Keeffe, Sean, Banerjee, Nilanjana, Li, Dadong, Watanabe, Kyoko, Marketta, Anthony, Van Meter, Michael, Semrau, Stefan, Horowitz, Julie, Tang, Jing, Kosmicki, Jack A., Rajagopal, Veera M., Zou, Yuxin, Houvras, Yariv, Ghosh, Arkopravo, Gillies, Christopher, Mbatchou, Joelle, White, Ryan R., Verweij, Niek, Bovijn, Jonas, Parikshak, Neelroop N., LeBlanc, Michelle G., Jones, Marcus, Glass, David J., Lotta, Luca A., Cantor, Michael N., Atwal, Gurinder S., Locke, Adam E., Ferreira, Manuel A. R., Deering, Raquel, Paulding, Charles, Shuldiner, Alan R., Thurston, Gavin, Ferrando, Adolfo A., Salerno, Will, Reid, Jeffrey G., Overton, John D., Marchini, Jonathan, Kang, Hyun M., Baras, Aris, Abecasis, Gonçalo R., and Jorgenson, Eric

Published
2023
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16. Genetic analyses identify widespread sex-differential participation bias

Author

Pirastu, Nicola, Cordioli, Mattia, Nandakumar, Priyanka, Mignogna, Gianmarco, Abdellaoui, Abdel, Hollis, Benjamin, Kanai, Masahiro, Rajagopal, Veera M., Parolo, Pietro Della Briotta, Baya, Nikolas, Carey, Caitlin E., Karjalainen, Juha, Als, Thomas D., Van der Zee, Matthijs D., Day, Felix R., Ong, Ken K., Morisaki, Takayuki, de Geus, Eco, Bellocco, Rino, Okada, Yukinori, Børglum, Anders D., Joshi, Peter, Auton, Adam, Hinds, David, Neale, Benjamin M., Walters, Raymond K., Nivard, Michel G., Perry, John R. B., and Ganna, Andrea

Published
2021
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17. Risky Business: Human Genetics Improves Drug Development Success.

Author

Rajagopal, Veera M.

Subjects
*HUMAN genetics, *DRUG development, *GENETIC databases
Abstract

A study published in Nature by Matt Nelson and colleagues provides evidence that human genetics is crucial for improving the success rates of drug development. The study found that less than 10% of drugs that enter clinical development succeed, resulting in high costs for drug developers. Drugs often fail due to lack of efficacy or adverse effects, which can be better understood through human genetics. By including human genetics evidence in the decision-making process, drug companies can double their success rate from 10% to 20%. The study also highlights the need for continued investment in human genetics research to further improve drug success rates. However, it is important to note that the identification of an association between a gene and a disease does not necessarily mean that the gene is a good drug target. The study has some limitations, such as hindsight and selection biases, but real-world experiences of drug companies implementing genetics-based drug target prioritization may offer further confirmation of the impact of human genetics on clinical success. [Extracted from the article]

Published
2024
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18. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains:[Inkl. Correction]

Author

Demontis, Ditte, Walters, G. Bragi, Athanasiadis, Georgios, Walters, Raymond, Therrien, Karen, Nielsen, Trine Tollerup, Farajzadeh, Leila, Voloudakis, Georgios, Bendl, Jaroslav, Zeng, Biau, Zhang, Wen, Grove, Jakob, Als, Thomas D., Duan, Jinjie, Satterstrom, F. Kyle, Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Gudmundsson, Olafur O., Magnusson, Sigurdur H., Baldursson, Gisli, Davidsdottir, Katrin, Haraldsdottir, Gyda S., Agerbo, Esben, Hoffman, Gabriel E., Dalsgaard, Søren, Martin, Joanna, Ribasés, Marta, Boomsma, Dorret I., Soler Artigas, Maria, Roth Mota, Nina, Howrigan, Daniel, Medland, Sarah E., Zayats, Tetyana, Rajagopal, Veera M., Havdahl, Alexandra, Doyle, Alysa, Reif, Andreas, Thapar, Anita, Cormand, Bru, Liao, Calwing, Burton, Christie, Bau, Claiton H.D., Rovaris, Diego Luiz, Sonuga-Barke, Edmund, Corfield, Elizabeth, Grevet, Eugenio Horacio, Larsson, Henrik, Gizer, Ian R., Nordentoft, Merete, Werge, Thomas, Demontis, Ditte, Walters, G. Bragi, Athanasiadis, Georgios, Walters, Raymond, Therrien, Karen, Nielsen, Trine Tollerup, Farajzadeh, Leila, Voloudakis, Georgios, Bendl, Jaroslav, Zeng, Biau, Zhang, Wen, Grove, Jakob, Als, Thomas D., Duan, Jinjie, Satterstrom, F. Kyle, Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Gudmundsson, Olafur O., Magnusson, Sigurdur H., Baldursson, Gisli, Davidsdottir, Katrin, Haraldsdottir, Gyda S., Agerbo, Esben, Hoffman, Gabriel E., Dalsgaard, Søren, Martin, Joanna, Ribasés, Marta, Boomsma, Dorret I., Soler Artigas, Maria, Roth Mota, Nina, Howrigan, Daniel, Medland, Sarah E., Zayats, Tetyana, Rajagopal, Veera M., Havdahl, Alexandra, Doyle, Alysa, Reif, Andreas, Thapar, Anita, Cormand, Bru, Liao, Calwing, Burton, Christie, Bau, Claiton H.D., Rovaris, Diego Luiz, Sonuga-Barke, Edmund, Corfield, Elizabeth, Grevet, Eugenio Horacio, Larsson, Henrik, Gizer, Ian R., Nordentoft, Merete, and Werge, Thomas

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84–98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.

Published
2023

19. 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

22. Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Author

Eising, Else, primary, Mirza-Schreiber, Nazanin, additional, de Zeeuw, Eveline L., additional, Wang, Carol A., additional, Truong, Dongnhu T., additional, Allegrini, Andrea G., additional, Shapland, Chin Yang, additional, Zhu, Gu, additional, Wigg, Karen G., additional, Gerritse, Margot L., additional, Molz, Barbara, additional, Alagöz, Gökberk, additional, Gialluisi, Alessandro, additional, Abbondanza, Filippo, additional, Rimfeld, Kaili, additional, van Donkelaar, Marjolein, additional, Liao, Zhijie, additional, Jansen, Philip R., additional, Andlauer, Till F. M., additional, Bates, Timothy C., additional, Bernard, Manon, additional, Blokland, Kirsten, additional, Bonte, Milene, additional, Børglum, Anders D., additional, Bourgeron, Thomas, additional, Brandeis, Daniel, additional, Ceroni, Fabiola, additional, Csépe, Valéria, additional, Dale, Philip S., additional, de Jong, Peter F., additional, DeFries, John C., additional, Démonet, Jean-François, additional, Demontis, Ditte, additional, Feng, Yu, additional, Gordon, Scott D., additional, Guger, Sharon L., additional, Hayiou-Thomas, Marianna E., additional, Hernández-Cabrera, Juan A., additional, Hottenga, Jouke-Jan, additional, Hulme, Charles, additional, Kere, Juha, additional, Kerr, Elizabeth N., additional, Koomar, Tanner, additional, Landerl, Karin, additional, Leonard, Gabriel T., additional, Lovett, Maureen W., additional, Lyytinen, Heikki, additional, Martin, Nicholas G., additional, Martinelli, Angela, additional, Maurer, Urs, additional, Michaelson, Jacob J., additional, Moll, Kristina, additional, Monaco, Anthony P., additional, Morgan, Angela T., additional, Nöthen, Markus M., additional, Pausova, Zdenka, additional, Pennell, Craig E., additional, Pennington, Bruce F., additional, Price, Kaitlyn M., additional, Rajagopal, Veera M., additional, Ramus, Franck, additional, Richer, Louis, additional, Simpson, Nuala H., additional, Smith, Shelley D., additional, Snowling, Margaret J., additional, Stein, John, additional, Strug, Lisa J., additional, Talcott, Joel B., additional, Tiemeier, Henning, additional, van der Schroeff, Marc P., additional, Verhoef, Ellen, additional, Watkins, Kate E., additional, Wilkinson, Margaret, additional, Wright, Margaret J., additional, Barr, Cathy L., additional, Boomsma, Dorret I., additional, Carreiras, Manuel, additional, Franken, Marie-Christine J., additional, Gruen, Jeffrey R., additional, Luciano, Michelle, additional, Müller-Myhsok, Bertram, additional, Newbury, Dianne F., additional, Olson, Richard K., additional, Paracchini, Silvia, additional, Paus, Tomáš, additional, Plomin, Robert, additional, Reilly, Sheena, additional, Schulte-Körne, Gerd, additional, Tomblin, J. Bruce, additional, van Bergen, Elsje, additional, Whitehouse, Andrew J. O., additional, Willcutt, Erik G., additional, St Pourcain, Beate, additional, Francks, Clyde, additional, and Fisher, Simon E., additional

Published
2022
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23. Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Author

Eising, Else, Mirza-Schreiber, Nazanin, de Zeeuw, Eveline L., Wang, Carol A., Truong, Dongnhu T., Allegrini, Andrea G., Shapland, Chin Yang, Zhu Gu, Wigg, Karen G., Gerritse, Margot, Molz, Barbara, Alagöz, Gökberk, Gialluisi, Alessandro, Abbondanza, Filippo, Rimfeld, Kaili, van Donkelaar, Marjolein, Liao Zhijie, Jansen, Philip R., Andlauer, Till F.M., Bates, Timothy C., Bernard, Manon, Blokland, Kirsten, Bonte, Milene, Børglum Anders D., Bourgeron, Thomas, Brandeis, Daniel, Ceroni, Fabiola, Csépe, Valeria, Dale, Philip S., de Jong, Peter F., DeFries, John C., Demontis, Ditte, Feng Yu, Gordon, Scott D., Guger, Sharon L., Hayiou-Thomas, Marianna E., Hernández-Cabrera, Juan A., Hottenga, Jouke-Jan, Hulme, Charles, Kere, Juha, Kerr, Elizabeth N., Koomar, Tanner, Landerl, Karin, Leonard, Gabriel, Lovett, Maureen W., Lyytinen, Heikki, Martin, Nicholas G., Martinelli, Angela, Maurer, Urs, Michaelson, Jacob J., Moll, Kristina, Monaco, Anthnony P., Morgan, Angela T., Noethen, Markus M., Pausova, Zdenka, Pennell, Craig E., Pennington, Bruce F., Price, Kaitlyn M., Rajagopal, Veera M., Ramus, Franck, Richer, Louis, Simpson, Nuala H., Smith, Shelley, Snowling, Margaret J., Stein, John, Strug, Lisa J., Talcott, Joel B., Tiemeier, Henning, van der Schroeff, Marc M.P., Verhoef, Ellen, Watkins, Kate E., Wilkinson, Margaret, Wright, Margaret J., Barr, Cathy L., Boomsma, Dorret I., Carreiras, Manuel, Franken, Marie-Christine J., Gruen, Jeffrey R., Luciano, Michelle, Müller-Myhsok, Bertram, Newbury, Dianne F., Olson, Richard K., Paracchini, Silvia, Paus, Tomas, Plomin, Robert, Reilly, Sheena, Schulte-Körne, Gerd, Tomblin, Bruce, van Bergen, Elsje, Whitehouse, Andrew J.O., Willcutt, Erik G., St Pourcain, Beate, Francks, Clyde, Fisher, Simon E., Eising, Else, Mirza-Schreiber, Nazanin, de Zeeuw, Eveline L., Wang, Carol A., Truong, Dongnhu T., Allegrini, Andrea G., Shapland, Chin Yang, Zhu Gu, Wigg, Karen G., Gerritse, Margot, Molz, Barbara, Alagöz, Gökberk, Gialluisi, Alessandro, Abbondanza, Filippo, Rimfeld, Kaili, van Donkelaar, Marjolein, Liao Zhijie, Jansen, Philip R., Andlauer, Till F.M., Bates, Timothy C., Bernard, Manon, Blokland, Kirsten, Bonte, Milene, Børglum Anders D., Bourgeron, Thomas, Brandeis, Daniel, Ceroni, Fabiola, Csépe, Valeria, Dale, Philip S., de Jong, Peter F., DeFries, John C., Demontis, Ditte, Feng Yu, Gordon, Scott D., Guger, Sharon L., Hayiou-Thomas, Marianna E., Hernández-Cabrera, Juan A., Hottenga, Jouke-Jan, Hulme, Charles, Kere, Juha, Kerr, Elizabeth N., Koomar, Tanner, Landerl, Karin, Leonard, Gabriel, Lovett, Maureen W., Lyytinen, Heikki, Martin, Nicholas G., Martinelli, Angela, Maurer, Urs, Michaelson, Jacob J., Moll, Kristina, Monaco, Anthnony P., Morgan, Angela T., Noethen, Markus M., Pausova, Zdenka, Pennell, Craig E., Pennington, Bruce F., Price, Kaitlyn M., Rajagopal, Veera M., Ramus, Franck, Richer, Louis, Simpson, Nuala H., Smith, Shelley, Snowling, Margaret J., Stein, John, Strug, Lisa J., Talcott, Joel B., Tiemeier, Henning, van der Schroeff, Marc M.P., Verhoef, Ellen, Watkins, Kate E., Wilkinson, Margaret, Wright, Margaret J., Barr, Cathy L., Boomsma, Dorret I., Carreiras, Manuel, Franken, Marie-Christine J., Gruen, Jeffrey R., Luciano, Michelle, Müller-Myhsok, Bertram, Newbury, Dianne F., Olson, Richard K., Paracchini, Silvia, Paus, Tomas, Plomin, Robert, Reilly, Sheena, Schulte-Körne, Gerd, Tomblin, Bruce, van Bergen, Elsje, Whitehouse, Andrew J.O., Willcutt, Erik G., St Pourcain, Beate, Francks, Clyde, and Fisher, Simon E.

Abstract

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, in samples of 13,633 to 33,959 participants aged 5-26 years. We identified genome-wide significant association with word reading (rs11208009, p=1.098 x 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP-heritability, accounting for 13-26% of trait variability. Genomic structural equation modelling revealed a shared genetic factor explaining most variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain, and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of uniquely human traits.

Published
2022

24. Rare coding variants in CHRNB2reduce the likelihood of smoking

Author

Rajagopal, Veera M., Watanabe, Kyoko, Mbatchou, Joelle, Ayer, Ariane, Quon, Peter, Sharma, Deepika, Kessler, Michael D., Praveen, Kavita, Gelfman, Sahar, Parikshak, Neelroop, Otto, Jacqueline M., Bao, Suying, Chim, Shek Man, Pavlopoulos, Elias, Avbersek, Andreja, Kapoor, Manav, Chen, Esteban, Jones, Marcus B., Leblanc, Michelle, Emberson, Jonathan, Collins, Rory, Torres, Jason, Morales, Pablo Kuri, Tapia-Conyer, Roberto, Alegre, Jesus, Berumen, Jaime, Shuldiner, Alan R., Balasubramanian, Suganthi, Abecasis, Gonçalo R., Kang, Hyun M., Marchini, Jonathan, Stahl, Eli A., Jorgenson, Eric, Sanchez, Robert, Liedtke, Wolfgang, Anderson, Matthew, Cantor, Michael, Lederer, David, Baras, Aris, and Coppola, Giovanni

Abstract

Human genetic studies of smoking behavior have been thus far largely limited to common variants. Studying rare coding variants has the potential to identify drug targets. We performed an exome-wide association study of smoking phenotypes in up to 749,459 individuals and discovered a protective association in CHRNB2, encoding the β2 subunit of the α4β2 nicotine acetylcholine receptor. Rare predicted loss-of-function and likely deleterious missense variants in CHRNB2in aggregate were associated with a 35% decreased odds for smoking heavily (odds ratio (OR) = 0.65, confidence interval (CI) = 0.56–0.76, P= 1.9 × 10−8). An independent common variant association in the protective direction (rs2072659; OR = 0.96; CI = 0.94–0.98; P= 5.3 × 10−6) was also evident, suggesting an allelic series. Our findings in humans align with decades-old experimental observations in mice that β2 loss abolishes nicotine-mediated neuronal responses and attenuates nicotine self-administration. Our genetic discovery will inspire future drug designs targeting CHRNB2in the brain for the treatment of nicotine addiction.

Published
2023
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25. Genome-wide association study and multi-trait analysis of opioid use disorder identifies novel associations in 639,709 individuals of European and African ancestry

Author

Deak, Joseph D., primary, Zhou, Hang, additional, Galimberti, Marco, additional, Levey, Daniel, additional, Wendt, Frank R., additional, Sanchez-Roige, Sandra, additional, Hatoum, Alexander, additional, Johnson, Emma C., additional, Nunez, Yaira Z., additional, Demontis, Ditte, additional, Børglum, Anders D., additional, Rajagopal, Veera M., additional, Jennings, Mariela V., additional, Kember, Rachel L., additional, Justice, Amy C., additional, Edenberg, Howard J., additional, Agrawal, Arpana, additional, Polimanti, Renato, additional, Kranzler, Henry R., additional, and Gelernter, Joel, additional

Published
2021
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26. Polygenic liability, stressful life events and risk for secondary-treated depression in early life: a nationwide register-based case-cohort study.

Author

Musliner, Katherine L., Andersen, Klaus K., Agerbo, Esben, Albiñana, Clara, Vilhjalmsson, Bjarni J., Rajagopal, Veera M., Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Pedersen, Carsten B., Pedersen, Marianne G., Munk-Olsen, Trine, Benros, Michael E., Als, Thomas D., Grove, Jakob, Werge, Thomas, Børglum, Anders D., Hougaard, David M., Mors, Ole, Nordentoft, Merete, and Mortensen, Preben B.

Subjects
MENTAL depression risk factors, LIFE change events, HOSPITAL emergency services, AGE distribution, CASE-control method, RISK assessment, SEX distribution, MENTAL depression, AGE factors in disease, HOSPITAL care, RESEARCH funding, DESCRIPTIVE statistics, PSYCHOLOGICAL stress, PSYCHIATRIC hospitals, LONGITUDINAL method, PROPORTIONAL hazards models
Abstract

Background: In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark. Methods: Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions. Results: Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15. Conclusions: These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Genome-wide association analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Author

Eising, Else, primary, Mirza-Schreiber, Nazanin, additional, de Zeeuw, Eveline L., additional, Wang, Carol A., additional, Truong, Dongnhu T., additional, Allegrini, Andrea G., additional, Shapland, Chin Yang, additional, Zhu, Gu, additional, Wigg, Karen G., additional, Gerritse, Margot, additional, Molz, Barbara, additional, Alagöz, Gökberk, additional, Gialluisi, Alessandro, additional, Abbondanza, Filippo, additional, Rimfeld, Kaili, additional, van Donkelaar, Marjolein, additional, Liao, Zhijie, additional, Jansen, Philip R., additional, Andlauer, Till F. M., additional, Bates, Timothy C., additional, Bernard, Manon, additional, Blokland, Kirsten, additional, Børglum, Anders D., additional, Bourgeron, Thomas, additional, Brandeis, Daniel, additional, Ceroni, Fabiola, additional, Dale, Philip S., additional, Landerl, Karin, additional, Lyytinen, Heikki, additional, de Jong, Peter F., additional, DeFries, John C., additional, Demontis, Ditte, additional, Feng, Yu, additional, Gordon, Scott D., additional, Guger, Sharon L., additional, Hayiou-Thomas, Marianna E., additional, Hernández-Cabrera, Juan A., additional, Hottenga, Jouke-Jan, additional, Hulme, Charles, additional, Kerr, Elizabeth N., additional, Koomar, Tanner, additional, Lovett, Maureen W., additional, Martin, Nicholas G., additional, Martinelli, Angela, additional, Maurer, Urs, additional, Michaelson, Jacob J., additional, Moll, Kristina, additional, Monaco, Anthony P., additional, Morgan, Angela T., additional, Nöthen, Markus M., additional, Pausova, Zdenka, additional, Pennell, Craig E., additional, Pennington, Bruce F, additional, Price, Kaitlyn M., additional, Rajagopal, Veera M., additional, Ramus, Frank, additional, Richer, Louis, additional, Simpson, Nuala H., additional, Smith, Shelley, additional, Snowling, Margaret J., additional, Stein, John, additional, Strug, Lisa J., additional, Talcott, Joel B., additional, Tiemeier, Henning, additional, van de Schroeff, Marc M.P., additional, Verhoef, Ellen, additional, Watkins, Kate E., additional, Wilkinson, Margaret, additional, Wright, Margaret J., additional, Barr, Cathy L., additional, Boomsma, Dorret I., additional, Carreiras, Manuel, additional, Franken, Marie-Christine J., additional, Gruen, Jeffrey R., additional, Luciano, Michelle, additional, Müller-Myhsok, Bertram, additional, Newbury, Dianne F., additional, Olson, Richard K., additional, Paracchini, Silvia, additional, Paus, Tomas, additional, Plomin, Robert, additional, Schulte-Körne, Gerd, additional, Reilly, Sheena, additional, Tomblin, J. Bruce, additional, van Bergen, Elsje, additional, Whitehouse, Andrew J.O., additional, Willcutt, Erik G., additional, Pourcain, Beate St, additional, Francks, Clyde, additional, and Fisher, Simon E., additional

Published
2021
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29. Genome-wide by environment interaction study of stressful life events and hospital-treated depression in the iPSYCH2012 sample

Author

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

Published
2021
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30. Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention deficit hyperactivity disorder

Author

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

Published
2021
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31. Author Correction: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

Author

Demontis, Ditte, Walters, Raymond K, Rajagopal, Veera M, Waldman, Irwin D, Grove, Jakob, Als, Thomas D, Dalsgaard, Søren, Ribasés, Marta, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Maria, Werge, Thomas, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, Cormand, Bru, Hougaard, David M, Neale, Benjamin M, Franke, Barbara, Faraone, Stephen V, Børglum, Anders D, et al, Steinhausen, Hans-Christoph, University of Zurich, Demontis, Ditte, Faraone, Stephen V, and Børglum, Anders D

Subjects
1300 General Biochemistry, Genetics and Molecular Biology, 610 Medicine & health, 1600 General Chemistry, 10058 Department of Child and Adolescent Psychiatry, 3100 General Physics and Astronomy
Published
2021

32. Author Correction:Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder (Nature communications (2021) 12 1 (576))

Author

Demontis, Ditte, Walters, Raymond K., Rajagopal, Veera M., Waldman, Irwin D., Grove, Jakob, Als, Thomas D., Dalsgaard, Søren, Ribasés, Marta, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Maria, Werge, Thomas, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, Cormand, Bru, Hougaard, David M., Neale, Benjamin M., Franke, Barbara, Faraone, Stephen V., and Børglum, Anders D.

Published
2021

33. Author Correction: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder (Nature Communications, (2021), 12, 1, (576), 10.1038/s41467-020-20443-2)

Author

Demontis, Ditte, Walters, Raymond K., Rajagopal, Veera M., Waldman, Irwin D., Grove, Jakob, Als, Thomas D., Dalsgaard, Søren, Ribasés, Marta, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Maria, Werge, Thomas, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, Andreassen, Ole A., Arranz, Maria Jesús, Banaschewski, Tobias, Bau, Claiton, Bellgrove, Mark, Biederman, Joseph, Brikell, Isabell, Buitelaar, Jan K., Burton, Christie L., Casas, Miguel, Crosbie, Jennifer, Doyle, Alysa E., Ebstein, Richard P., Elia, Josephine, Elizabeth, Corfield C., Grevet, Eugenio, Grizenko, Natalie, Havdahl, Alexandra, Hawi, Ziarih, Hebebrand, Johannes, Hervas, Amaia, Hohmann, Sarah, Haavik, Jan, Joober, Ridha, Kent, Lindsey, Kuntsi, Jonna, Langley, Kate, Larsson, Henrik, Lesch, Klaus-Peter, Leung, Patrick W. L., Liao, Calwing, Loo, Sandra K., Martin, Joanna, Martin, Nicholas G., Medland, Sarah E., Miranda, Ana, Mota, Nina Roth, Oades, Robert D., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Rietschel, Marcella, Roeyers, Herbert, Rohde, Luis Augusto, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Schachar, Russell James, Sengupta, Sarojini, Artigas, Maria Soler, Steinhausen, Hans-Christoph, Thapar, Anita, Witt, Stephanie H., Yang, Li, Zayats, Tetyana, Zhang-James, Yanli, Cormand, Bru, Hougaard, David M., Neale, Benjamin M., Franke, Barbara, Faraone, Stephen V., and Børglum, Anders D.

Subjects
Medizin
Abstract

The original version of this Article contained an error in the spelling of the author Marta Ribasés, which was incorrectly given as Marta Ribasas. This has now been corrected in both the PDF and HTML versions of the Article. CA extern, Korrektur zu: 10.1038/s41467-020-20443-2

Published
2021

34. Identification of genetic loci associated with nocturnal enuresis:a genome-wide association study

Author

Jørgensen, Cecilie S., Horsdal, Henriette T., Rajagopal, Veera M., Grove, Jakob, Als, Thomas D., Kamperis, Konstantinos, Nyegaard, Mette, Walters, G. Bragi, Eðvarðsson, Viðar Örn, Stefánsson, Hreinn, Nordentoft, Merete, Hougaard, David Michael, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Agerbo, Esben, Rittig, Søren, Stefánsson, Kári, Børglum, Anders D., Demontis, Ditte, Christensen, Jane H., Jørgensen, Cecilie S., Horsdal, Henriette T., Rajagopal, Veera M., Grove, Jakob, Als, Thomas D., Kamperis, Konstantinos, Nyegaard, Mette, Walters, G. Bragi, Eðvarðsson, Viðar Örn, Stefánsson, Hreinn, Nordentoft, Merete, Hougaard, David Michael, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Agerbo, Esben, Rittig, Søren, Stefánsson, Kári, Børglum, Anders D., Demontis, Ditte, and Christensen, Jane H.

Abstract

Background: Nocturnal enuresis (bedwetting) is a common disorder affecting 10–16% of 7-year-old children globally. Nocturnal enuresis is highly heritable, but its genetic determinants remain unknown. We aimed to identify genetic variants associated with nocturnal enuresis and explore its genetic architecture and underlying biology. Methods: We did a genome-wide association study (GWAS) of nocturnal enuresis. Nocturnal enuresis cases were identified in iPSYCH2012, a large Danish population-based case cohort established to investigate mental disorders, on the basis of 10th revision of the International Statistical Classification of Diseases (ICD-10) diagnoses and redeemed desmopressin prescriptions in Danish registers. The GWAS was done in a genetically homogeneous sample of unrelated individuals using logistic regression with relevant covariates. All genome-wide significant variants were analysed for their association with nocturnal enuresis in an independent Icelandic sample from deCODE genetics. Standardised polygenic risk scores for attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder were constructed from summary statistics of large GWASs and analysed for association with nocturnal enuresis. Findings: The GWAS included 3882 nocturnal enuresis cases and 31 073 controls. We found two loci at chromosome 6 and chromosome 13 significantly associated with nocturnal enuresis. Six genetic variants at the two loci (five variants at chromosome 6q16.2 and one variant at chromosome 13q22.3) surpassed the threshold for genome-wide significance (p<5 × 10−8). There were two lead variants: rs9376454 (chromosome 6q16.2), with an odds ratio (OR) of 1·199 (95% CI 1·135–1·267; p=9·91 × 10−11), and rs60721117 (chromosome 13q22.3), with an OR of 1·149 (1·095–1·205; p=1·21 × 10−8). All associated variants in the chromosome 6 locus were replicated (p<8 × 10−3) in the independent Icelandic cohort of 5475 nocturn

Published
2021

35. Author Correction: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

Author

Demontis, Ditte; https://orcid.org/0000-0001-9124-2766, Walters, Raymond K; https://orcid.org/0000-0001-8422-6530, Rajagopal, Veera M; https://orcid.org/0000-0002-5236-168X, Waldman, Irwin D; https://orcid.org/0000-0002-6862-1837, Grove, Jakob; https://orcid.org/0000-0003-2284-5744, Als, Thomas D; https://orcid.org/0000-0002-2963-1928, Dalsgaard, Søren; https://orcid.org/0000-0003-4659-0969, Ribasés, Marta; https://orcid.org/0000-0003-1039-1116, Bybjerg-Grauholm, Jonas; https://orcid.org/0000-0003-1705-4008, Bækvad-Hansen, Maria, Werge, Thomas; https://orcid.org/0000-0003-1829-0766, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, Cormand, Bru, Hougaard, David M; https://orcid.org/0000-0001-5928-3517, Neale, Benjamin M; https://orcid.org/0000-0003-1513-6077, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, Faraone, Stephen V, Børglum, Anders D; https://orcid.org/0000-0001-8627-7219, et al, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Demontis, Ditte; https://orcid.org/0000-0001-9124-2766, Walters, Raymond K; https://orcid.org/0000-0001-8422-6530, Rajagopal, Veera M; https://orcid.org/0000-0002-5236-168X, Waldman, Irwin D; https://orcid.org/0000-0002-6862-1837, Grove, Jakob; https://orcid.org/0000-0003-2284-5744, Als, Thomas D; https://orcid.org/0000-0002-2963-1928, Dalsgaard, Søren; https://orcid.org/0000-0003-4659-0969, Ribasés, Marta; https://orcid.org/0000-0003-1039-1116, Bybjerg-Grauholm, Jonas; https://orcid.org/0000-0003-1705-4008, Bækvad-Hansen, Maria, Werge, Thomas; https://orcid.org/0000-0003-1829-0766, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, Cormand, Bru, Hougaard, David M; https://orcid.org/0000-0001-5928-3517, Neale, Benjamin M; https://orcid.org/0000-0003-1513-6077, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, Faraone, Stephen V, Børglum, Anders D; https://orcid.org/0000-0001-8627-7219, et al, and Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436

Published
2021

36. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

Author

Demontis, Ditte; https://orcid.org/0000-0001-9124-2766, Walters, Raymond K; https://orcid.org/0000-0001-8422-6530, Rajagopal, Veera M; https://orcid.org/0000-0002-5236-168X, Waldman, Irwin D; https://orcid.org/0000-0002-6862-1837, Grove, Jakob; https://orcid.org/0000-0003-2284-5744, Als, Thomas D; https://orcid.org/0000-0002-2963-1928, Dalsgaard, Søren; https://orcid.org/0000-0003-4659-0969, Ribasas, Marta; https://orcid.org/0000-0003-1039-1116, Bybjerg-Grauholm, Jonas; https://orcid.org/0000-0003-1705-4008, Bækvad-Hansen, Maria, Werge, Thomas; https://orcid.org/0000-0003-1829-0766, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, Cormand, Bru, Hougaard, David M; https://orcid.org/0000-0001-5928-3517, Neale, Benjamin M; https://orcid.org/0000-0003-1513-6077, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, Faraone, Stephen V, Børglum, Anders D; https://orcid.org/0000-0001-8627-7219, et al, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Demontis, Ditte; https://orcid.org/0000-0001-9124-2766, Walters, Raymond K; https://orcid.org/0000-0001-8422-6530, Rajagopal, Veera M; https://orcid.org/0000-0002-5236-168X, Waldman, Irwin D; https://orcid.org/0000-0002-6862-1837, Grove, Jakob; https://orcid.org/0000-0003-2284-5744, Als, Thomas D; https://orcid.org/0000-0002-2963-1928, Dalsgaard, Søren; https://orcid.org/0000-0003-4659-0969, Ribasas, Marta; https://orcid.org/0000-0003-1039-1116, Bybjerg-Grauholm, Jonas; https://orcid.org/0000-0003-1705-4008, Bækvad-Hansen, Maria, Werge, Thomas; https://orcid.org/0000-0003-1829-0766, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, Cormand, Bru, Hougaard, David M; https://orcid.org/0000-0001-5928-3517, Neale, Benjamin M; https://orcid.org/0000-0003-1513-6077, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, Faraone, Stephen V, Børglum, Anders D; https://orcid.org/0000-0001-8627-7219, et al, and Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10-10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.

Published
2021

37. Identification of genetic loci associated with nocturnal enuresis: a genome-wide association study

Author

Jørgensen, Cecilie S, primary, Horsdal, Henriette T, additional, Rajagopal, Veera M, additional, Grove, Jakob, additional, Als, Thomas D, additional, Kamperis, Konstantinos, additional, Nyegaard, Mette, additional, Walters, G Bragi, additional, Eðvarðsson, Viðar Örn, additional, Stefánsson, Hreinn, additional, Nordentoft, Merete, additional, Hougaard, David Michael, additional, Werge, Thomas, additional, Mors, Ole, additional, Mortensen, Preben Bo, additional, Agerbo, Esben, additional, Rittig, Søren, additional, Stefánsson, Kári, additional, Børglum, Anders D, additional, Demontis, Ditte, additional, and Christensen, Jane H, additional

Published
2021
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38. Genome-wide association study of school grades identifies a genetic overlap between language ability, psychopathology and creativity

Author

Rajagopal, Veera M., Ganna, Andrea, Coleman, Jonathan R. I., Allegrini, Andrea G., Voloudakis, Georgios, Grove, Jakob, Als, Thomas D., Horsdal, Henriette T., Petersen, Liselotte, Appadurai, Vivek, Schork, Andrew, Buil, Alfonso, Bulik, Cynthia M., Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Hougaard, David M., Mors, Ole, Nordentoft, Merete, Werge, Thomas, Consortium, iPSYCH-Broad, Mortensen, Preben Bo, Breen, Gerome, Roussos, Panos, Plomin, Robert, Agerbo, Esben, Børglum, Anders D., and Demontis, Ditte

Subjects
0303 health sciences, education.field_of_study, media_common.quotation_subject, Population, education, Cognition, Genome-wide association study, Creativity, Educational attainment, language.human_language, Danish, 03 medical and health sciences, 0302 clinical medicine, language, Association (psychology), 030217 neurology & neurosurgery, 030304 developmental biology, Clinical psychology, media_common, Psychopathology
Abstract

Individuals with psychiatric disorders perform differently in school compared to the general population. Genetic factors contribute substantially to such differences. It is however unclear if differential performance is seen across all cognitive domains such as math and language. Here we report a genome-wide association study (GWAS) of school grades in 30,982 individuals (18,495 with and 12,487 without one or more of six major psychiatric disorders) and a replication study in 4,547 individuals. GWAS of overall school performance yielded results that were highly similar to the results of a previous GWAS of educational attainment. Analyzing subject specific grades, we observed that math performance was severely affected whereas language performance (Danish and English) was relatively unaffected or enhanced in those with psychiatric disorders compared to controls. We found that the genetic variants associated with poor math performance, but better language performance were also associated with increased risk for multiple psychiatric disorders. The same variants were also associated with creativity, which we show through a polygenic score analysis of 2953 creative professionals and 164,622 controls. The results overall suggest that risk for psychiatric disorders, language ability and creativity might have overlapping genetic roots.

Published
2020
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39. Genetic analyses identify widespread sex-differential participation bias

Author

Pirastu, Nicola, Cordioli, Mattia, Nandakumar, Priyanka, Mignogna, Gianmarco, Abdellaoui, Abdel, Hollis, Benjamin, Kanai, Masahiro, Rajagopal, Veera M., Della Briotta Parolo, Pietro, Baya, Nikolas, Carey, Caitlin, Karjalainen, Juha, Als, Thomas D., Van der Zee, Matthijs D., Day, Felix R., Ong, Ken K., Study, Finngen, Morisaki, Takayuki, de Geus, Eco, Bellocco, Rino, Okada, Yukinori, Børglum, Anders D., Joshi, Peter, Auton, Adam, Hinds, David, Neale, Benjamin M., Walters, Raymond K., Nivard, Michel G., Perry, John R.B., Ganna, Andrea, and Adult Psychiatry

Subjects
0303 health sciences, Participation bias, Locus (genetics), Genome-wide association study, Heritability, Biology, 03 medical and health sciences, 0302 clinical medicine, Sample size determination, Allele, 10. No inequality, Body mass index, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association, Demography
Abstract

Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of this participation bias is challenging as it requires the genotypes of unseen individuals. However, we demonstrate that it is possible to estimate comparative biases by performing GWAS contrasting one subgroup versus another. For example, we show that sex exhibits autosomal heritability in the presence of sex-differential participation bias. By performing a GWAS of sex in ~3.3 million males and females, we identify over 158 autosomal loci significantly associated with sex and highlight complex traits underpinning differences in study participation between sexes. For example, the body mass index (BMI) increasing allele at the FTO locus was observed at higher frequency in males compared to females (OR 1.02 [1.02-1.03], P=4.4×10−36). Finally, we demonstrate how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

Published
2020

40. Polygenic prediction of school performance in individuals with and without psychiatric disorders

Author

Rajagopal, Veera M., Trajberg, Betina B., Grove, Jakob, Horsdal, Henriette T., Petersen, Liselotte, Bulik, Cynthia M., Bybjerg-Grauholm, Jonas, Baekvad-Hansen, Marie, Hougaard, David M., Mors, Ole, Nordentoft, Merete, Werge, Thomas, Mortensen, Preben Bo, Agerbo, Esben, Borglum, Anders D., Demontis, Ditte, Rajagopal, Veera M., Trajberg, Betina B., Grove, Jakob, Horsdal, Henriette T., Petersen, Liselotte, Bulik, Cynthia M., Bybjerg-Grauholm, Jonas, Baekvad-Hansen, Marie, Hougaard, David M., Mors, Ole, Nordentoft, Merete, Werge, Thomas, Mortensen, Preben Bo, Agerbo, Esben, Borglum, Anders D., and Demontis, Ditte

Published
2020

41. Polygenic prediction of school performance in children with and without psychiatric disorders

Author

Rajagopal, Veera M., primary, Trabjerg, Betina B, additional, Grove, Jakob, additional, Horsdal, Henriette T., additional, Petersen, Liselotte, additional, Bulik, Cynthia M., additional, Bybjerg-Grauholm, Jonas, additional, Bækvad-Hansen, Marie, additional, Hougaard, David M, additional, Mors, Ole, additional, Nordentoft, Merete, additional, Werge, Thomas, additional, Mortensen, Preben Bo, additional, Agerbo, Esben, additional, Borglum, Anders D., additional, and Demontis, Ditte, additional

Published
2020
Full Text
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42. Publisher Correction: Gene expression imputation across multiple brain regions provides insights into schizophrenia risk (Nature Genetics, (2019), 51, 4, (659-674), 10.1038/s41588-019-0364-4)

Author

Huckins, Laura M., Dobbyn, Amanda, Ruderfer, Douglas M., Hoffman, Gabriel, Wang, Weiqing, Pardiñas, Antonio F., Rajagopal, Veera M., Als, Thomas D., t. Nguyen, Hoang, Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R., Purcell, Shaun, Demontis, Ditte, Børglum, Anders D., Walters, James T. R., C. O’Donovan, Michael, Sullivan, Patrick, Owen, Michael J., Devlin, Bernie, Sieberts, Solveig K., Cox, Nancy J., Im, Hae Kyung, Sklar, Pamela, and Stahl, Eli A.

Subjects
health services administration, genetic processes, information science, natural sciences, health care economics and organizations
Abstract

In the HTML version of the article originally published, the author group ‘The Schizophrenia Working Group of the Psychiatric Genomics Consortium’ was displayed incorrectly. The error has been corrected in the HTML version of the article.

Published
2019

43. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Author

Huckins, Laura M. Dobbyn, Amanda Ruderfer, Douglas M. and Hoffman, Gabriel Wang, Weiqing Pardinas, Antonio F. and Rajagopal, Veera M. Als, Thomas D. Nguyen, Hoang T. Girdhar, Kiran Boocock, James Roussos, Panos Fromer, Menachem and Kramer, Robin Domenici, Enrico Gamazon, Eric R. Purcell, Shaun Demontis, Ditte Borglum, Anders D. Walters, James T. R. O'Donovan, Michael C. Sullivan, Patrick Owen, Michael J. and Devlin, Bernie Sieberts, Solveig K. Cox, Nancy J. Im, Hae Kyung Sklar, Pamela Stahl, Eli A. Johnson, Jessica S. and Shah, Hardik R. Klein, Lambertus L. Dang, Kristen K. and Logsdon, Benjamin A. Mahajan, Milind C. Mangravite, Lara M. and Toyoshiba, Hiroyoshi Gur, Raquel E. Hahn, Chang-Gyu Schadt, Eric Lewis, David A. Haroutunian, Vahram Peters, Mette A. and Lipska, Barbara K. Buxbaum, Joseph D. Hirai, Keisuke and Perumal, Thanneer M. Essioux, Laurent Rajagopal, Veera Manikandan Mattheisen, Manuel Grove, Jakob Werge, Thomas and Mortensen, Preben Bo Pedersen, Carsten Bocker Agerbo, Esben and Pedersen, Marianne Giortz Mors, Ole Nordentoft, Merete and Hougaard, David M. Bybjerg-Grauholm, Jonas Baekvad-Hansen, Marie and Hansen, Christine Soholm Ripke, Stephan Neale, Benjamin M. and Corvin, Aiden Farh, Kai-How Holmans, Peter A. Lee, Phil and Bulik-Sullivan, Brendan Collier, David A. Huang, Hailiang and Pers, Tune H. Agartz, Ingrid Albus, Margot Alexander, Madeline Amin, Farooq Bacanu, Silviu A. Begemann, Martin and Belliveau, Jr., Richard A. Bene, Judit Bergen, Sarah E. and Bevilacqua, Elizabeth Bigdeli, Tim B. Black, Donald W. and Bruggeman, Richard Buccola, Nancy G. Buckner, Randy L. and Byerley, William Cahn, Wiepke Cai, Guiqing Campion, Dominique Cantor, Rita M. Carr, Vaughan J. Carrera, Noa and Catts, V, Stanley Chambert, Kimberly D. Chan, Raymond C. K. and Chen, Ronald Y. L. Chen, Eric Y. H. Cheng, Wei Cheung, Eric F. C. Chong, Siow Ann Cloninger, C. Robert Cohen, David and Cohen, Nadine Cormican, Paul Craddock, Nick Crowley, James J. Curtis, David Davidson, Michael Davis, Kenneth L. and Degenhardt, Franziska Del Favero, Jurgen Dikeos, Dimitris and Dinan, Timothy Djurovic, Srdjan Donohoe, Gary Drapeau, Elodie Duan, Jubao Dudbridge, Frank Durmishi, Naser and Eichhammer, Peter Eriksson, Johan Escott-Price, Valentina and Essioux, Laurent Fanous, Ayman H. Farrell, Martilias S. and Frank, Josef Franke, Lude Freedman, Robert Freimer, Nelson B. Friedl, Marion Friedman, I, Joseph Fromer, Menachem and Genovese, Giulio Georgieva, Lyudmila Giegling, Ina and Giusti-Rodriguez, Paola Godard, Stephanie Goldstein, I, Jacqueline Golimbet, Vera Gopal, Srihari Gratten, Jacob and de Haan, Lieuwe Hammer, Christian Hamshere, Marian L. and Hansen, Mark Hansen, Thomas Haroutunian, Vahram Hartmann, Annette M. Henskens, Frans A. Herms, Stefan Hirschhorn, Joel N. Hoffmann, Per Hofman, Andrea Hollegaard, V, Mads and Ikeda, Masashi Joa, Inge Julia, Antonio Kahn, Rene S. and Kalaydjieva, Luba Karachanak-Yankova, Sena Karjalainen, Juha and Kavanagh, David Keller, Matthew C. Kennedy, James L. and Khrunin, Andrey Kim, Yunjung Klovins, Janis Knowles, James A. Konte, Bettina Kucinskas, Vaidutis Kucinskiene, Zita Ausrele Kuzelova-Ptackova, Hana Kahler, Anna K. Laurent, Claudine Keong, Jimmy Lee Chee Lee, S. Hong Legge, Sophie E. and Lerer, Bernard Li, Miaoxin Li, Tao Liang, Kung-Yee and Lieberman, Jeffrey Limborska, Svetlana Loughland, Carmel M. and Lubinski, Jan Lonnqvist, Jouko Macek, Jr., Milan Magnusson, Patrik K. E. Maher, Brion S. Maier, Wolfgang Mallet, Jacques and Marsal, Sara Mattingsdal, Morten McCarley, Robert W. and McDonald, Colm McIntosh, Andrew M. Meier, Sandra Meijer, Carin J. Melegh, Bela Melle, Ingrid Mesholam-Gately, I, Raquelle Metspalu, Andres Michie, Patricia T. Milani, Lili and Milanova, Vihra Mokrab, Younes Morris, Derek W. Mors, Ole Murphy, Kieran C. Murray, Robin M. Myin-Germeys, Inez and Muller-Myhsok, Bertram Nelis, Mari Nenadic, Igor and Nertney, Deborah A. Nestadt, Gerald Nicodemus, Kristin K. and Nikitina-Zake, Liene Nisenbaum, Laura Nordin, Annelie and O'Callaghan, Eadbhard O'Dushlaine, Colm O'Neill, F. Anthony and Oh, Sang-Yun Olincy, Ann Olsen, Line Van Os, Jim and Pantelis, Christos Papadimitriou, George N. Papiol, Sergi and Parkhomenko, Elena Pato, Michele T. Paunio, Tiina and Pejovic-Milovancevic, Milica Perkins, Diana O. Pietilainen, Olli and Pimm, Jonathan Pocklington, Andrew J. Powell, John and Price, Alkes Pulver, Ann E. Purcell, Shaun M. Quested, Digby and Rasmussen, Henrik B. Reichenberg, Abraham Reimers, Mark A. and Richards, Alexander L. Roffman, Joshua L. Ruderfer, Douglas M. Salomaa, Veikko Sanders, Alan R. Schall, Ulrich and Schubert, Christian R. Schulze, Thomas G. Schwab, Sibylle G. and 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. and So, Hon-Cheong Spencer, Chris C. A. Stefansson, Hreinn and Steinberg, Stacy Stogmann, Elisabeth Straub, Richard E. and Strengman, Eric Strohmaier, Jana Stroup, T. Scott and Subramaniam, Mythily Suvisaari, Jaana Svrakic, Dragan M. and Szatkiewicz, Jin P. Soderman, Erik Thirumalai, Srinivas and Toncheva, Draga Tosato, Sarah Veijola, Juha Waddington, John and Walsh, Dermot Wang, Dai Wang, Qiang Webb, Bradley T. and Weiser, Mark Wildenauer, Dieter B. Williams, Nigel M. and 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. and Stefansson, Kari Visscher, Peter M. Adolfsson, Rolf and Andreassen, Ole A. Blackwood, Douglas H. R. Bramon, Elvira and Buxbaum, Joseph D. Borglum, Anders D. Cichon, Sven Darvasi, Ariel Domenici, Enrico Ehrenreich, Hannelore Esko, Tonu and Gejman, V, Pablo Gill, Michael Gurling, Hugh Hultman, Christina M. Iwata, Nakao Jablensky, V, Assen Jonsson, Erik G. Kendler, Kenneth S. Kirov, George Knight, Jo Lencz, Todd Levinson, Douglas F. Li, Qingqin S. Liu, Jianjun and Malhotra, Anil K. McCarroll, Steven A. McQuillin, Andrew and Moran, Jennifer L. Mortensen, Preben B. Mowry, Bryan J. and Nothen, 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 and Sham, Pak C. St Clair, David Weinberger, Daniel R. and Wendland, Jens R. Werge, Thomas Daly, Mark J. Sullivan, Patrick F. CommonMind Consortium Psychiat Genomics Consortium and iPSYCH-GEMS Schizophrenia Working

Abstract

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

Published
2019

44. Publisher Correction:Gene expression imputation across multiple brain regions provides insights into schizophrenia risk (Nature Genetics, (2019), 51, 4, (659-674), 10.1038/s41588-019-0364-4)

Author

Huckins, Laura M., Dobbyn, Amanda, Ruderfer, Douglas M., Hoffman, Gabriel, Wang, Weiqing, Pardiñas, Antonio F., Rajagopal, Veera M., Als, Thomas D., T. Nguyen, Hoang, Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R., Purcell, Shaun, Johnson, Jessica S., Shah, Hardik R., Klein, Lambertus L., Dang, Kristen K., Logsdon, Benjamin A., Mahajan, Milind C., Agerbo, Esben, Demontis, Ditte, Hansen, Mark, Hansen, Thomas, Hollegaard, Mads V., Mattheisen, Manuel, Meier, Sandra, Mors, Ole, Rasmussen, Henrik B., Stahl, Eli A., Børglum, Anders D., Mortensen, Preben Bo, Grove, Jakob, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, and Hansen, Christine Søholm

Abstract

In the HTML version of the article originally published, the author group ‘The Schizophrenia Working Group of the Psychiatric Genomics Consortium’ was displayed incorrectly. The error has been corrected in the HTML version of the article.

Published
2019

45. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Author

Huckins, Laura M., Dobbyn, Amanda, Ruderfer, Douglas M., Hoffman, Gabriel, Wang, Weiqing, Pardinas, Antonio F., Rajagopal, Veera M., Als, Thomas D., Nguyen, Hoang T., Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R., Purcell, Shaun, Demontis, Ditte, Borglum, Anders D., Walters, James T. R., O'Donovan, Michael C., Sullivan, Patrick, Owen, Michael J., Devlin, Bernie, Sieberts, Solveig K., Cox, Nancy J., Im, Hae Kyung, Sklar, Pamela, Stahl, Eli A., Johnson, Jessica S., Shah, Hardik R., Klein, Lambertus L., Dang, Kristen K., Logsdon, Benjamin A., Mahajan, Milind C., Mangravite, Lara M., Toyoshiba, Hiroyoshi, Gur, Raquel E., Hahn, Chang-Gyu, Schadt, Eric, Lewis, David A., Haroutunian, Vahram, Peters, Mette A., Lipska, Barbara K., Buxbaum, Joseph D., Hirai, Keisuke, Perumal, Thanneer M., Essioux, Laurent, Rajagopal, Veera Manikandan, Mattheisen, Manuel, Grove, Jakob, Werge, Thomas, Mortensen, Preben Bo, Pedersen, Carsten Bocker, Agerbo, Esben, Pedersen, Marianne Giortz, Mors, Ole, Nordentoft, Merete, Hougaard, David M., Bybjerg-Grauholm, Jonas, Baekvad-Hansen, Marie, Hansen, Christine Soholm, Ripke, Stephan, Neale, Benjamin M., Corvin, Aiden, Farh, Kai-How, Holmans, Peter A., Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, 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, Kimberly D., Chan, Raymond C. K., Chen, Ronald Y. L., Chen, Eric Y. H., Cheng, Wei, Cheung, Eric F. C., 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, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Fanous, Ayman H., Farrell, Martilias S., Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph, I, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodriguez, Paola, Godard, Stephanie, Goldstein, Jacqueline, I, Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads, V, Ikeda, Masashi, Joa, Inge, Julia, Antonio, Kahn, Rene 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, Kahler, Anna K., Laurent, Claudine, Keong, Jimmy Lee Chee, Lee, S. Hong, Legge, Sophie E., Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lonnqvist, Jouko, Macek, Milan, Jr., Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, 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., Murphy, Kieran C., Murray, Robin M., Myin-Germeys, Inez, Muller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin Adolfsson, 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., Pietilainen, 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., 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., 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., Soderman, 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, Cichon, Sven, Darvasi, Ariel, Ehrenreich, Hannelore, Esko, Tonu, Gejman, Pablo, V, Gill, Michael, Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen, V, Jonsson, 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., Nothen, Markus M., Ophoff, Roel A., Palotie, Aarno, Pato, Carlos N., Petryshen, Tracey L., Posthuma, Danielle, Rietschel, Marcella, Riley, Brien P., Rujescu, Dan, Sham, Pak C., St Clair, David, Weinberger, Daniel R., Wendland, Jens R., Daly, Mark J., Sullivan, Patrick F., Huckins, Laura M., Dobbyn, Amanda, Ruderfer, Douglas M., Hoffman, Gabriel, Wang, Weiqing, Pardinas, Antonio F., Rajagopal, Veera M., Als, Thomas D., Nguyen, Hoang T., Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R., Purcell, Shaun, Demontis, Ditte, Borglum, Anders D., Walters, James T. R., O'Donovan, Michael C., Sullivan, Patrick, Owen, Michael J., Devlin, Bernie, Sieberts, Solveig K., Cox, Nancy J., Im, Hae Kyung, Sklar, Pamela, Stahl, Eli A., Johnson, Jessica S., Shah, Hardik R., Klein, Lambertus L., Dang, Kristen K., Logsdon, Benjamin A., Mahajan, Milind C., Mangravite, Lara M., Toyoshiba, Hiroyoshi, Gur, Raquel E., Hahn, Chang-Gyu, Schadt, Eric, Lewis, David A., Haroutunian, Vahram, Peters, Mette A., Lipska, Barbara K., Buxbaum, Joseph D., Hirai, Keisuke, Perumal, Thanneer M., Essioux, Laurent, Rajagopal, Veera Manikandan, Mattheisen, Manuel, Grove, Jakob, Werge, Thomas, Mortensen, Preben Bo, Pedersen, Carsten Bocker, Agerbo, Esben, Pedersen, Marianne Giortz, Mors, Ole, Nordentoft, Merete, Hougaard, David M., Bybjerg-Grauholm, Jonas, Baekvad-Hansen, Marie, Hansen, Christine Soholm, Ripke, Stephan, Neale, Benjamin M., Corvin, Aiden, Farh, Kai-How, Holmans, Peter A., Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, 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, Kimberly D., Chan, Raymond C. K., Chen, Ronald Y. L., Chen, Eric Y. H., Cheng, Wei, Cheung, Eric F. C., 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, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Fanous, Ayman H., Farrell, Martilias S., Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph, I, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodriguez, Paola, Godard, Stephanie, Goldstein, Jacqueline, I, Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads, V, Ikeda, Masashi, Joa, Inge, Julia, Antonio, Kahn, Rene 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, Kahler, Anna K., Laurent, Claudine, Keong, Jimmy Lee Chee, Lee, S. Hong, Legge, Sophie E., Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lonnqvist, Jouko, Macek, Milan, Jr., Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, 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., Murphy, Kieran C., Murray, Robin M., Myin-Germeys, Inez, Muller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin Adolfsson, 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., Pietilainen, 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., 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., 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., Soderman, 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, Cichon, Sven, Darvasi, Ariel, Ehrenreich, Hannelore, Esko, Tonu, Gejman, Pablo, V, Gill, Michael, Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen, V, Jonsson, 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., Nothen, Markus M., Ophoff, Roel A., Palotie, Aarno, Pato, Carlos N., Petryshen, Tracey L., Posthuma, Danielle, Rietschel, Marcella, Riley, Brien P., Rujescu, Dan, Sham, Pak C., St Clair, David, Weinberger, Daniel R., Wendland, Jens R., Daly, Mark J., and Sullivan, Patrick F.

Abstract

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

Published
2019
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46. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Author

Onderzoek, Brain, Onderzoeksgroep 11, Hersenen-Medisch 1, Hersenen-Bedrijfsvoering, Huckins, Laura M., Dobbyn, Amanda, Ruderfer, Douglas M., Hoffman, Gabriel, Wang, Weiqing, Pardinas, Antonio F., Rajagopal, Veera M., Als, Thomas D., Nguyen, Hoang T., Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R., Purcell, Shaun, Demontis, Ditte, Borglum, Anders D., Walters, James T. R., O'Donovan, Michael C., Sullivan, Patrick, Owen, Michael J., Devlin, Bernie, Sieberts, Solveig K., Cox, Nancy J., Im, Hae Kyung, Sklar, Pamela, Stahl, Eli A., Johnson, Jessica S., Shah, Hardik R., Klein, Lambertus L., Dang, Kristen K., Logsdon, Benjamin A., Mahajan, Milind C., Mangravite, Lara M., Toyoshiba, Hiroyoshi, Gur, Raquel E., Hahn, Chang-Gyu, Schadt, Eric, Lewis, David A., Haroutunian, Vahram, Peters, Mette A., Lipska, Barbara K., Buxbaum, Joseph D., Hirai, Keisuke, Cahn, Wiepke, Kahn, Rene S., Van Os, Jim, Ophoff, Roel A., Onderzoek, Brain, Onderzoeksgroep 11, Hersenen-Medisch 1, Hersenen-Bedrijfsvoering, Huckins, Laura M., Dobbyn, Amanda, Ruderfer, Douglas M., Hoffman, Gabriel, Wang, Weiqing, Pardinas, Antonio F., Rajagopal, Veera M., Als, Thomas D., Nguyen, Hoang T., Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R., Purcell, Shaun, Demontis, Ditte, Borglum, Anders D., Walters, James T. R., O'Donovan, Michael C., Sullivan, Patrick, Owen, Michael J., Devlin, Bernie, Sieberts, Solveig K., Cox, Nancy J., Im, Hae Kyung, Sklar, Pamela, Stahl, Eli A., Johnson, Jessica S., Shah, Hardik R., Klein, Lambertus L., Dang, Kristen K., Logsdon, Benjamin A., Mahajan, Milind C., Mangravite, Lara M., Toyoshiba, Hiroyoshi, Gur, Raquel E., Hahn, Chang-Gyu, Schadt, Eric, Lewis, David A., Haroutunian, Vahram, Peters, Mette A., Lipska, Barbara K., Buxbaum, Joseph D., Hirai, Keisuke, Cahn, Wiepke, Kahn, Rene S., Van Os, Jim, and Ophoff, Roel A.

Published
2019

47. Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits

Author

Zhang, Wen, primary, Voloudakis, Georgios, additional, Rajagopal, Veera M., additional, Readhead, Ben, additional, Dudley, Joel T., additional, Schadt, Eric E., additional, Björkegren, Johan L. M., additional, Kim, Yungil, additional, Fullard, John F., additional, Hoffman, Gabriel E., additional, and Roussos, Panos, additional

Published
2019
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49. Genome-wide by Environment Interaction Study of Stressful Life Events and Hospital-Treated Depression in the iPSYCH2012 Sample.

Author

Suppli NP, Andersen KK, Agerbo E, Rajagopal VM, Appadurai V, Coleman JRI, Breen G, Bybjerg-Grauholm J, Bækvad-Hansen M, Pedersen CB, Pedersen MG, Thompson WK, Munk-Olsen T, Benros ME, Als TD, Grove J, Werge T, Børglum AD, Hougaard DM, Mors O, Nordentoft M, Mortensen PB, and Musliner KL

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., (© 2021 The Authors.)

Published
2021
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