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2. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder

Author

Nievergelt, Caroline M., Maihofer, Adam X., Atkinson, Elizabeth G., Chen, Chia-Yen, Choi, Karmel W., Coleman, Jonathan R. I., Daskalakis, Nikolaos P., Duncan, Laramie E., Polimanti, Renato, Aaronson, Cindy, Amstadter, Ananda B., Andersen, Soren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegoviç, Esmina, Babić, Dragan, Bacanu, Silviu-Alin, Baker, Dewleen G., Batzler, Anthony, Beckham, Jean C., Belangero, Sintia, Benjet, Corina, Bergner, Carisa, Bierer, Linda M., Biernacka, Joanna M., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Brandolino, Amber, Breen, Gerome, Bressan, Rodrigo Affonseca, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Børglum, Anders D., Børte, Sigrid, Cahn, Leah, Calabrese, Joseph R., Caldas-de-Almeida, Jose Miguel, Chatzinakos, Chris, Cheema, Sheraz, Clouston, Sean A. P., Colodro-Conde, Lucía, Coombes, Brandon J., Cruz-Fuentes, Carlos S., Dale, Anders M., Dalvie, Shareefa, Davis, Lea K., Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Desarnaud, Frank, DiPietro, Christopher P., Disner, Seth G., Docherty, Anna R., Domschke, Katharina, Dyb, Grete, Kulenović, Alma Džubur, Edenberg, Howard J., Evans, Alexandra, Fabbri, Chiara, Fani, Negar, Farrer, Lindsay A., Feder, Adriana, Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F., Goleva, Slavina B., Gordon, Scott D., Goçi, Aferdita, Grasser, Lana Ruvolo, Guindalini, Camila, Haas, Magali, Hagenaars, Saskia, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M. J., Hesselbrock, Victor, Hickie, Ian B., Hogan, Kelleigh, Hougaard, David Michael, Huang, Hailiang, Huckins, Laura M., Hveem, Kristian, Jakovljević, Miro, Javanbakht, Arash, Jenkins, Gregory D., Johnson, Jessica, Jones, Ian, Jovanovic, Tanja, Karstoft, Karen-Inge, Kaufman, Milissa L., Kennedy, James L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kotov, Roman, Kranzler, Henry R., Krebs, Kristi, Kremen, William S., Kuan, Pei-Fen, Lawford, Bruce R., Lebois, Lauren A. M., Lehto, Kelli, Levey, Daniel F., Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D., Logue, Mark W., Lori, Adriana, Lu, Yi, Luft, Benjamin J., Lupton, Michelle K., Luykx, Jurjen J., Makotkine, Iouri, Maples-Keller, Jessica L., Marchese, Shelby, Marmar, Charles, Martin, Nicholas G., Martínez-Levy, Gabriela A., McAloney, Kerrie, McFarlane, Alexander, McLaughlin, Katie A., McLean, Samuel A., Medland, Sarah E., Mehta, Divya, Meyers, Jacquelyn, Michopoulos, Vasiliki, Mikita, Elizabeth A., Milani, Lili, Milberg, William, Miller, Mark W., Morey, Rajendra A., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben Bo, Mufford, Mary S., Nelson, Elliot C., Nordentoft, Merete, Norman, Sonya B., Nugent, Nicole R., O’Donnell, Meaghan, Orcutt, Holly K., Pan, Pedro M., Panizzon, Matthew S., Pathak, Gita A., Peters, Edward S., Peterson, Alan L., Peverill, Matthew, Pietrzak, Robert H., Polusny, Melissa A., Porjesz, Bernice, Powers, Abigail, Qin, Xue-Jun, Ratanatharathorn, Andrew, Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Kenneth J., Rung, Ariane, Runz, Heiko, Rutten, Bart P. F., de Viteri, Stacey Saenz, Salum, Giovanni Abrahão, Sampson, Laura, Sanchez, Sixto E., Santoro, Marcos, Seah, Carina, Seedat, Soraya, Seng, Julia S., Shabalin, Andrey, Sheerin, Christina M., Silove, Derrick, Smith, Alicia K., Smoller, Jordan W., Sponheim, Scott R., Stein, Dan J., Stensland, Synne, Stevens, Jennifer S., Sumner, Jennifer A., Teicher, Martin H., Thompson, Wesley K., Tiwari, Arun K., Trapido, Edward, Uddin, Monica, Ursano, Robert J., Valdimarsdóttir, Unnur, Van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan H., Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Waszczuk, Monika, Weber, Heike, Wendt, Frank R., Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winsvold, Bendik S., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Xia, Yan, Xiong, Ying, Yehuda, Rachel, Young, Keith A., Young, Ross McD, Zai, Clement C., Zai, Gwyneth C., Zervas, Mark, Zhao, Hongyu, Zoellner, Lori A., Zwart, John-Anker, deRoon-Cassini, Terri, van Rooij, Sanne J. H., van den Heuvel, Leigh L., Stein, Murray B., Ressler, Kerry J., and Koenen, Karestan C.

Published
2024
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3. Construction of extra-large scale screening tools for risks of severe mental illnesses using real world healthcare data

Author

Liu, Dianbo, Choi, Karmel W., Lizano, Paulo, Yuan, William, Yu, Kun-Hsing, Smoller, Jordan W., and Kohane, Isaac

Subjects
Computer Science - Artificial Intelligence, Quantitative Biology - Quantitative Methods
Abstract

Importance: The prevalence of severe mental illnesses (SMIs) in the United States is approximately 3% of the whole population. The ability to conduct risk screening of SMIs at large scale could inform early prevention and treatment. Objective: A scalable machine learning based tool was developed to conduct population-level risk screening for SMIs, including schizophrenia, schizoaffective disorders, psychosis, and bipolar disorders,using 1) healthcare insurance claims and 2) electronic health records (EHRs). Design, setting and participants: Data from beneficiaries from a nationwide commercial healthcare insurer with 77.4 million members and data from patients from EHRs from eight academic hospitals based in the U.S. were used. First, the predictive models were constructed and tested using data in case-control cohorts from insurance claims or EHR data. Second, performance of the predictive models across data sources were analyzed. Third, as an illustrative application, the models were further trained to predict risks of SMIs among 18-year old young adults and individuals with substance associated conditions. Main outcomes and measures: Machine learning-based predictive models for SMIs in the general population were built based on insurance claims and EHR.

Published
2022

4. Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury.

Author

Stein, Murray B, Jain, Sonia, Parodi, Livia, Choi, Karmel W, Maihofer, Adam X, Nelson, Lindsay D, Mukherjee, Pratik, Sun, Xiaoying, He, Feng, Okonkwo, David O, Giacino, Joseph T, Korley, Frederick K, Vassar, Mary J, Robertson, Claudia S, McCrea, Michael A, Temkin, Nancy, Markowitz, Amy J, Diaz-Arrastia, Ramon, Rosand, Jonathan, Manley, Geoffrey T, and TRACK-TBI Investigators

Subjects
TRACK-TBI Investigators, Humans, Brain Concussion, Longitudinal Studies, Prospective Studies, Stress Disorders, Post-Traumatic, Depressive Disorder, Major, Traumatic Head and Spine Injury, Mental Health, Post-Traumatic Stress Disorder (PTSD), Neurosciences, Brain Disorders, Physical Injury - Accidents and Adverse Effects, Anxiety Disorders, Clinical Research, Traumatic Brain Injury (TBI), Serious Mental Illness, Mental health, Good Health and Well Being, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80-7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual's PRS could be clinically actionable if used-possibly with other non-genetic predictors-to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.

Published
2023

6. Anxiety and Depression Associated With Increased Cardiovascular Disease Risk Through Accelerated Development of Risk Factors

Author

Civieri, Giovanni, Abohashem, Shady, Grewal, Simran S., Aldosoky, Wesam, Qamar, Iqra, Hanlon, Erin, Choi, Karmel W., Shin, Lisa M., Rosovsky, Rachel P., Bollepalli, Sandeep Chandra, Lau, Hui Chong, Armoundas, Antonis A., Seligowski, Antonia V., Turgeon, Sarah M., Pitman, Roger K., Tona, Francesco, Wasfy, Jason H., Smoller, Jordan W., Iliceto, Sabino, Goldstein, Jill, Gebhard, Catherine, Osborne, Michael T., and Tawakol, Ahmed

Published
2024
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13. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author

Maihofer, Adam X, Choi, Karmel W, Coleman, Jonathan RI, Daskalakis, Nikolaos P, Denckla, Christy A, Ketema, Elizabeth, Morey, Rajendra A, Polimanti, Renato, Ratanatharathorn, Andrew, Torres, Katy, Wingo, Aliza P, Zai, Clement C, Aiello, Allison E, Almli, Lynn M, Amstadter, Ananda B, Andersen, Soren B, Andreassen, Ole A, Arbisi, Paul A, Ashley-Koch, Allison E, Austin, S Bryn, Avdibegović, Esmina, Borglum, Anders D, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G, Beckham, Jean C, Bierut, Laura J, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Bradley, Bekh, Brashear, Meghan, Breen, Gerome, Bryant, Richard A, Bustamante, Angela C, Bybjerg-Grauholm, Jonas, Calabrese, Joseph R, Caldas-de-Almeida, José M, Chen, Chia-Yen, Dale, Anders M, Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L, Dennis, Michelle F, Disner, Seth G, Domschke, Katharina, Duncan, Laramie E, Džubur Kulenović, Alma, Erbes, Christopher R, Evans, Alexandra, Farrer, Lindsay A, Feeny, Norah C, Flory, Janine D, Forbes, David, Franz, Carol E, Galea, Sandro, Garrett, Melanie E, Gautam, Aarti, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F, Goçi, Aferdita, Gordon, Scott D, Guffanti, Guia, Hammamieh, Rasha, Hauser, Michael A, Heath, Andrew C, Hemmings, Sian MJ, Hougaard, David Michael, Jakovljević, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Karstoft, Karen-Inge, Kaufman, Milissa L, Kessler, Ronald C, Khan, Alaptagin, Kimbrel, Nathan A, King, Anthony P, Koen, Nastassja, Kranzler, Henry R, Kremen, William S, Lawford, Bruce R, Lebois, Lauren AM, Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D, Logue, Mark W, Lori, Adriana, Lugonja, Božo, Luykx, Jurjen J, Lyons, Michael J, Maples-Keller, Jessica L, Marmar, Charles, Martin, Nicholas G, Maurer, Douglas, and Mavissakalian, Matig R

Subjects
Biological Sciences, Genetics, Anxiety Disorders, Mental Health, Brain Disorders, Post-Traumatic Stress Disorder (PTSD), Prevention, Human Genome, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide, Stress Disorders, Post-Traumatic, GWAS, Heritability, PTSD, PheWAS, Trauma, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract

BackgroundPosttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs).MethodsA GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms.ResultsGWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program.ConclusionsThrough using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

Published
2022

19. An Exposure-Wide and Mendelian Randomization Approach to Identifying Modifiable Factors for the Prevention of Depression

Author

Choi, Karmel W, Stein, Murray B, Nishimi, Kristen M, Ge, Tian, Coleman, Jonathan RI, Chen, Chia-Yen, Ratanatharathorn, Andrew, Zheutlin, Amanda B, Dunn, Erin C, Breen, Gerome, Koenen, Karestan C, and Smoller, Jordan W

Subjects
Clinical Research, Brain Disorders, Prevention, Depression, Mental Health, Behavioral and Social Science, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Good Health and Well Being, Adult, Databases as Topic, Diet, Exercise, Female, Humans, Male, Mendelian Randomization Analysis, Multifactorial Inheritance, Risk Factors, Screen Time, Sleep Hygiene, 23andMe Research Team, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Exposome, Mendelian Randomization, Polygenic Risk, Protective Factors, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveEfforts to prevent depression, the leading cause of disability worldwide, have focused on a limited number of candidate factors. Using phenotypic and genomic data from over 100,000 UK Biobank participants, the authors sought to systematically screen and validate a wide range of potential modifiable factors for depression.MethodsBaseline data were extracted for 106 modifiable factors, including lifestyle (e.g., exercise, sleep, media, diet), social (e.g., support, engagement), and environmental (e.g., green space, pollution) variables. Incident depression was defined as minimal depressive symptoms at baseline and clinically significant depression at follow-up. At-risk individuals for incident depression were identified by polygenic risk scores or by reported traumatic life events. An exposure-wide association scan was conducted to identify factors associated with incident depression in the full sample and among at-risk individuals. Two-sample Mendelian randomization was then used to validate potentially causal relationships between identified factors and depression.ResultsNumerous factors across social, sleep, media, dietary, and exercise-related domains were prospectively associated with depression, even among at-risk individuals. However, only a subset of factors was supported by Mendelian randomization evidence, including confiding in others (odds ratio=0.76, 95% CI=0.67, 0.86), television watching time (odds ratio=1.09, 95% CI=1.05, 1.13), and daytime napping (odds ratio=1.34, 95% CI=1.17, 1.53).ConclusionsUsing a two-stage approach, this study validates several actionable targets for preventing depression. It also demonstrates that not all factors associated with depression in observational research may translate into robust targets for prevention. A large-scale exposure-wide approach combined with genetically informed methods for causal inference may help prioritize strategies for multimodal prevention in psychiatry.

Published
2020

20. Genomic influences on self-reported childhood maltreatment.

Author

Dalvie, Shareefa, Maihofer, Adam X, Coleman, Jonathan RI, Bradley, Bekh, Breen, Gerome, Brick, Leslie A, Chen, Chia-Yen, Choi, Karmel W, Duncan, Laramie E, Guffanti, Guia, Haas, Magali, Harnal, Supriya, Liberzon, Israel, Nugent, Nicole R, Provost, Allison C, Ressler, Kerry J, Torres, Katy, Amstadter, Ananda B, Bryn Austin, S, Baker, Dewleen G, Bolger, Elizabeth A, Bryant, Richard A, Calabrese, Joseph R, Delahanty, Douglas L, Farrer, Lindsay A, Feeny, Norah C, Flory, Janine D, Forbes, David, Galea, Sandro, Gautam, Aarti, Gelernter, Joel, Hammamieh, Rasha, Jett, Marti, Junglen, Angela G, Kaufman, Milissa L, Kessler, Ronald C, Khan, Alaptagin, Kranzler, Henry R, Lebois, Lauren AM, Marmar, Charles, Mavissakalian, Matig R, McFarlane, Alexander, Donnell, Meaghan O', Orcutt, Holly K, Pietrzak, Robert H, Risbrough, Victoria B, Roberts, Andrea L, Rothbaum, Alex O, Roy-Byrne, Peter, Ruggiero, Ken, Seligowski, Antonia V, Sheerin, Christina M, Silove, Derrick, Smoller, Jordan W, Stein, Murray B, Teicher, Martin H, Ursano, Robert J, Van Hooff, Miranda, Winternitz, Sherry, Wolff, Jonathan D, Yehuda, Rachel, Zhao, Hongyu, Zoellner, Lori A, Stein, Dan J, Koenen, Karestan C, and Nievergelt, Caroline M

Subjects
Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h2snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h2snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10-8, FOXP1; rs10262462, p = 3.24 × 10-8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h2snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r2 = 0.0025; p = 1.8 × 10-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rg = 0.70, p = 4.65 × 10-40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

Published
2020

22. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study

Author

Maihofer, Adam X., Choi, Karmel W., Coleman, Jonathan R.I., Daskalakis, Nikolaos P., Denckla, Christy A., Ketema, Elizabeth, Morey, Rajendra A., Polimanti, Renato, Ratanatharathorn, Andrew, Torres, Katy, Wingo, Aliza P., Zai, Clement C., Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Soren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Borglum, Anders D., Babic, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Bradley, Bekh, Brashear, Meghan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, Jose Miguel, Chen, Chia-Yen, Dale, Anders M., Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Duncan, Laramie E., Kulenovic, Alma Dzubur, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gautam, Aarti, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F., Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Karstoft, Karen-Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D., Logue, Mark W., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica L., Marmar, Charles, Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., Mehta, Divya, Mellor, Rebecca, Michopoulos, Vasiliki, Milberg, William, Miller, Mark W., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben Bo, Nelson, Elliot C., Nordentoft, Merete, Norman, Sonya B., O’Donnell, Meaghan, Orcutt, Holly K., Panizzon, Matthew S., Peters, Edward S., Peterson, Alan L., Peverill, Matthew, Pietrzak, Robert H., Polusny, Melissa A., Rice, John P., Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Kenneth J., Rung, Ariane, Rutten, Bart P.F., Saccone, Nancy L., Sanchez, Sixto E., Schijven, Dick, Seedat, Soraya, Seligowski, Antonia V., Seng, Julia S., Sheerin, Christina M., Silove, Derrick, Smith, Alicia K., Smoller, Jordan W., Sponheim, Scott R., Stein, Dan J., Stevens, Jennifer S., Teicher, Martin H., Thompson, Wesley K., Trapido, Edward, Uddin, Monica, Ursano, Robert J., Luella van den Heuvel, Leigh, Van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan, Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Yehuda, Rachel, Young, Keith A., Young, Ross McD., Zhao, Hongyu, Zoellner, Lori A., Haas, Magali, Lasseter, Heather, Provost, Allison C., Salem, Rany M., Sebat, Jonathan, Shaffer, Richard, Wu, Tianying, Ripke, Stephan, Daly, Mark J., Ressler, Kerry J., Koenen, Karestan C., Stein, Murray B., Nievergelt, Caroline M., Wendt, Frank R., Garcia-Argibay, Miguel, Cabrera-Mendoza, Brenda, Valdimarsdóttir, Unnur A., Nivard, Michel G., Larsson, Henrik, Mattheisen, Manuel, and Meier, Sandra M.

Published
2023
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23. Influence of Maternal Childhood Trauma on Perinatal Depression, Observed Mother-Infant Interactions, and Child Growth

Author

Choi, Karmel W., Denckla, Christy A., Hoffman, Nadia, Budree, Shrish, Goddard, Liz, Zar, Heather J., and Stern, Micky

Subjects
Psychic trauma in children -- Health aspects -- Social aspects, Mother and infant -- Psychological aspects -- Health aspects, Child development -- Social aspects -- Health aspects, Mothers -- Psychological aspects -- Health aspects -- Social aspects, Postpartum depression -- Risk factors -- Complications and side effects -- Social aspects, Health care industry
Abstract

Introduction Mothers who have experienced childhood trauma may be at increased risk for disruptions in caregiving behavior, with potential consequences for early child development. However, assessments of caregiving behavior tend to be self-reported, which may bias results, and have been limited in lower-resource settings. Methods In an overall sample of 256 South African mothers followed across the perinatal period, this longitudinal study used structural equation modeling to test pathways of association between maternal childhood trauma and depressive symptoms on observed mother-infant interactions at 3.5 months and subsequent child growth outcomes at 1 year. Results On average, mothers with childhood trauma histories tended to show lower rated overall interactions with their infants (B = - 0.16, p = .013), which in turn was associated with reduced child growth at 1 year (B = 0.17, p = .046). When this model was adjusted for maternal age and relative socioeconomic status (SES), maternal SES strongly explained child growth (B = 0.31, p < .001) such that the direct effect of mother-infant interactions was no longer significant. Discussion For child growth in a lower-resource setting, quality of mother-infant interactions could be a relevant predictor but more strongly explained by maternal SES factors, suggesting a need for broader approaches that not only improve dyadic relationships but also address maternal ecological resources., Author(s): Karmel W. Choi [sup.1] [sup.2] [sup.3] , Christy A. Denckla [sup.3] , Nadia Hoffman [sup.4] , Shrish Budree [sup.5] [sup.6] , Liz Goddard [sup.5] [sup.6] , Heather J. Zar [...]

Published
2022
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26. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

Author

Nievergelt, Caroline M, Maihofer, Adam X, Klengel, Torsten, Atkinson, Elizabeth G, Chen, Chia-Yen, Choi, Karmel W, Coleman, Jonathan RI, Dalvie, Shareefa, Duncan, Laramie E, Gelernter, Joel, Levey, Daniel F, Logue, Mark W, Polimanti, Renato, Provost, Allison C, Ratanatharathorn, Andrew, Stein, Murray B, Torres, Katy, Aiello, Allison E, Almli, Lynn M, Amstadter, Ananda B, Andersen, Søren B, Andreassen, Ole A, Arbisi, Paul A, Ashley-Koch, Allison E, Austin, S Bryn, Avdibegovic, Esmina, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G, Beckham, Jean C, Bierut, Laura J, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Børglum, Anders D, Bradley, Bekh, Brashear, Megan, Breen, Gerome, Bryant, Richard A, Bustamante, Angela C, Bybjerg-Grauholm, Jonas, Calabrese, Joseph R, Caldas-de-Almeida, José M, Dale, Anders M, Daly, Mark J, Daskalakis, Nikolaos P, Deckert, Jürgen, Delahanty, Douglas L, Dennis, Michelle F, Disner, Seth G, Domschke, Katharina, Dzubur-Kulenovic, Alma, Erbes, Christopher R, Evans, Alexandra, Farrer, Lindsay A, Feeny, Norah C, Flory, Janine D, Forbes, David, Franz, Carol E, Galea, Sandro, Garrett, Melanie E, Gelaye, Bizu, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D, Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, Hauser, Michael A, Heath, Andrew C, Hemmings, Sian MJ, Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Junglen, Angela G, Karstoft, Karen-Inge, Kaufman, Milissa L, Kessler, Ronald C, Khan, Alaptagin, Kimbrel, Nathan A, King, Anthony P, Koen, Nastassja, Kranzler, Henry R, Kremen, William S, Lawford, Bruce R, Lebois, Lauren AM, Lewis, Catrin E, Linnstaedt, Sarah D, Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J, Lyons, Michael J, Maples-Keller, Jessica, Marmar, Charles, and Martin, Alicia R

Subjects
Humans, Genetic Predisposition to Disease, Ubiquitin-Protein Ligases, Stress Disorders, Post-Traumatic, Sex Factors, African Continental Ancestry Group, European Continental Ancestry Group, Veterans, Female, Male, Genome-Wide Association Study, Genetic Loci, Datasets as Topic, Human Genome, Mental Health, Biotechnology, Clinical Research, Post-Traumatic Stress Disorder (PTSD), Anxiety Disorders, Prevention, Genetics
Abstract

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

Published
2019

29. Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations

Author

Ge, Tian, Irvin, Marguerite R., Patki, Amit, Srinivasasainagendra, Vinodh, Lin, Yen-Feng, Tiwari, Hemant K., Armstrong, Nicole D., Benoit, Barbara, Chen, Chia-Yen, Choi, Karmel W., Cimino, James J., Davis, Brittney H., Dikilitas, Ozan, Etheridge, Bethany, Feng, Yen-Chen Anne, Gainer, Vivian, Huang, Hailiang, Jarvik, Gail P., Kachulis, Christopher, Kenny, Eimear E., Khan, Atlas, Kiryluk, Krzysztof, Kottyan, Leah, Kullo, Iftikhar J., Lange, Christoph, Lennon, Niall, Leong, Aaron, Malolepsza, Edyta, Miles, Ayme D., Murphy, Shawn, Namjou, Bahram, Narayan, Renuka, O’Connor, Mark J., Pacheco, Jennifer A., Perez, Emma, Rasmussen-Torvik, Laura J., Rosenthal, Elisabeth A., Schaid, Daniel, Stamou, Maria, Udler, Miriam S., Wei, Wei-Qi, Weiss, Scott T., Ng, Maggie C. Y., Smoller, Jordan W., Lebo, Matthew S., Meigs, James B., Limdi, Nita A., and Karlson, Elizabeth W.

Published
2022
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33. Effect of Stress-Related Neural Pathways on the Cardiovascular Benefit of Physical Activity

Author

Zureigat, Hadil, primary, Osborne, Michael T., additional, Abohashem, Shady, additional, Mezue, Kenechukwu, additional, Gharios, Charbel, additional, Grewal, Simran, additional, Cardeiro, Alex, additional, Naddaf, Nicki, additional, Civieri, Giovanni, additional, Abbasi, Taimur, additional, Radfar, Azar, additional, Aldosoky, Wesam, additional, Seligowski, Antonia V., additional, Wasfy, Meagan M., additional, Guseh, James Sawalla, additional, Churchill, Timothy W., additional, Rosovsky, Rachel P., additional, Fayad, Zahi, additional, Rosenzweig, Anthony, additional, Baggish, Aaron, additional, Pitman, Roger K., additional, Choi, Karmel W., additional, Smoller, Jordan, additional, Shin, Lisa M., additional, and Tawakol, Ahmed, additional

Published
2024
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34. Interoperability of phenome-wide multimorbidity patterns: a comparative study of two large-scale EHR systems

Author

Strayer, Nick, primary, Vessels, Tess J., additional, Choi, Karmel W, additional, Zhang, Siwei, additional, Li, Yajing, additional, Sharber, Brian, additional, Hsi, Ryan S, additional, Bejan, Cosmin A, additional, Bick, Alexander G, additional, Balko, Justin M, additional, Johnson, Douglas B, additional, Wheless, Lee E, additional, Wells, Quinn S, additional, Shah, Ravi V, additional, Phillips, Elizabeth J, additional, Self, Wesley H., additional, Pulley, Jill M, additional, Wilkins, Consuelo H, additional, Chen, Qingxia, additional, Hartert, Tina, additional, Savona, Michael R, additional, Shyr, Yu, additional, Roden, Dan M, additional, Smoller, Jordan W, additional, Ruderfer, Douglas M, additional, and Xu, Yaomin, additional

Published
2024
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37. Potential causal association between gut microbiome and posttraumatic stress disorder

Author

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

Published
2024

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

Author

He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., Provost, Allison C., Ratanatharathorn, Andrew, Stein, Murray B., Torres, Katy, Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Søren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Børglum, Anders D., Bradley, Bekh, Brashear, Megan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, José M., Dale, Anders M., Daly, Mark J., Daskalakis, Nikolaos P., Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Dzubur-Kulenovic, Alma, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue Jun, Junglen, Angela G., Karstoft, Karen Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin E., Linnstaedt, Sarah D., Lori, Adriana, He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., Provost, Allison C., Ratanatharathorn, Andrew, Stein, Murray B., Torres, Katy, Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Søren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Børglum, Anders D., Bradley, Bekh, Brashear, Megan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, José M., Dale, Anders M., Daly, Mark J., Daskalakis, Nikolaos P., Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Dzubur-Kulenovic, Alma, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue Jun, Junglen, Angela G., Karstoft, Karen Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin E., Linnstaedt, Sarah D., and Lori, Adriana

Abstract

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.

Published
2024

43. Evaluating the impact of modeling choices on the performance of integrated genetic and clinical models

Author

Morley, Theodore J., primary, Willimitis, Drew, additional, Ripperger, Michael, additional, Lee, Hyunjoon, additional, Han, Lide, additional, Zhou, Yu, additional, Kang, Jooeun, additional, Davis, Lea K., additional, Smoller, Jordan W., additional, Choi, Karmel W., additional, Walsh, Colin G., additional, and Ruderfer, Douglas M., additional

Published
2023
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47. Social support and depression during a global crisis

Author

Choi, Karmel W., primary, Lee, Younga H., additional, Liu, Zhaowen, additional, Fatori, Daniel, additional, Bauermeister, Joshua R., additional, Luh, Rebecca A., additional, Clark, Cheryl R., additional, Brunoni, André R., additional, Bauermeister, Sarah, additional, and Smoller, Jordan W., additional

Published
2023
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