Browsing by Author "Kimbrel, Nathan A"
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Item Open Access An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci.(Clinical epigenetics, 2020-03) Logue, Mark W; Miller, Mark W; Wolf, Erika J; Huber, Bertrand Russ; Morrison, Filomene G; Zhou, Zhenwei; Zheng, Yuanchao; Smith, Alicia K; Daskalakis, Nikolaos P; Ratanatharathorn, Andrew; Uddin, Monica; Nievergelt, Caroline M; Ashley-Koch, Allison E; Baker, Dewleen G; Beckham, Jean C; Garrett, Melanie E; Boks, Marco P; Geuze, Elbert; Grant, Gerald A; Hauser, Michael A; Kessler, Ronald C; Kimbrel, Nathan A; Maihofer, Adam X; Marx, Christine E; Qin, Xue-Jun; Risbrough, Victoria B; Rutten, Bart PF; Stein, Murray B; Ursano, Robert J; Vermetten, Eric; Vinkers, Christiaan H; Ware, Erin B; Stone, Annjanette; Schichman, Steven A; McGlinchey, Regina E; Milberg, William P; Hayes, Jasmeet P; Verfaellie, Mieke; Traumatic Stress Brain Study GroupBackground
Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD).Methods
In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72).Results
The analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 × 10-7, padj = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 × 10-6), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 × 10-5, padj = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including "Response to lipopolysaccharide" (p = 6.97 × 10-6, padj = 0.042).Conclusions
The cross replication observed in independent cohorts is evidence that DNA methylation in peripheral tissue can yield consistent and replicable PTSD associations, and our results also suggest that that some PTSD associations observed in peripheral tissue may mirror associations in the brain.Item Open Access Gene Expression Analysis in Three Posttraumatic Stress Disorder Cohorts Implicates Inflammation and Innate Immunity Pathways and Uncovers Shared Genetic Risk With Major Depressive Disorder.(Frontiers in neuroscience, 2021-01) Garrett, Melanie E; Qin, Xue Jun; Mehta, Divya; Dennis, Michelle F; Marx, Christine E; Grant, Gerald A; VA Mid-Atlantic MIRECC Workgroup; PTSD Initiative; Injury and Traumatic Stress (INTRuST) Clinical Consortium; Psychiatric Genomics Consortium PTSD Group; Stein, Murray B; Kimbrel, Nathan A; Beckham, Jean C; Hauser, Michael A; Ashley-Koch, Allison EPosttraumatic stress disorder (PTSD) is a complex psychiatric disorder that can develop following exposure to traumatic events. The Psychiatric Genomics Consortium PTSD group (PGC-PTSD) has collected over 20,000 multi-ethnic PTSD cases and controls and has identified both genetic and epigenetic factors associated with PTSD risk. To further investigate biological correlates of PTSD risk, we examined three PGC-PTSD cohorts comprising 977 subjects to identify differentially expressed genes among PTSD cases and controls. Whole blood gene expression was quantified with the HumanHT-12 v4 Expression BeadChip for 726 OEF/OIF veterans from the Veterans Affairs (VA) Mental Illness Research Education and Clinical Center (MIRECC), 155 samples from the Injury and Traumatic Stress (INTRuST) Clinical Consortium, and 96 Australian Vietnam War veterans. Differential gene expression analysis was performed in each cohort separately followed by meta-analysis. In the largest cohort, we performed co-expression analysis to identify modules of genes that are associated with PTSD and MDD. We then conducted expression quantitative trait loci (eQTL) analysis and assessed the presence of eQTL interactions involving PTSD and major depressive disorder (MDD). Finally, we utilized PTSD and MDD GWAS summary statistics to identify regions that colocalize with eQTLs. Although not surpassing correction for multiple testing, the most differentially expressed genes in meta-analysis were interleukin-1 beta (IL1B), a pro-inflammatory cytokine previously associated with PTSD, and integrin-linked kinase (ILK), which is highly expressed in brain and can rescue dysregulated hippocampal neurogenesis and memory deficits. Pathway analysis revealed enrichment of toll-like receptor (TLR) and interleukin-1 receptor genes, which are integral to cellular innate immune response. Co-expression analysis identified four modules of genes associated with PTSD, two of which are also associated with MDD, demonstrating common biological pathways underlying the two conditions. Lastly, we identified four genes (UBA7, HLA-F, HSPA1B, and RERE) with high probability of a shared causal eQTL variant with PTSD and/or MDD GWAS variants, thereby providing a potential mechanism by which the GWAS variant contributes to disease risk. In summary, we provide additional evidence for genes and pathways previously reported and identified plausible novel candidates for PTSD. These data provide further insight into genetic factors and pathways involved in PTSD, as well as potential regions of pleiotropy between PTSD and MDD.Item Open Access GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.(The American journal of psychiatry, 2023-10) Docherty, Anna R; Mullins, Niamh; Ashley-Koch, Allison E; Qin, Xuejun; Coleman, Jonathan RI; Shabalin, Andrey; Kang, JooEun; Murnyak, Balasz; Wendt, Frank; Adams, Mark; Campos, Adrian I; DiBlasi, Emily; Fullerton, Janice M; Kranzler, Henry R; Bakian, Amanda V; Monson, Eric T; Rentería, Miguel E; Walss-Bass, Consuelo; Andreassen, Ole A; Behera, Chittaranjan; Bulik, Cynthia M; Edenberg, Howard J; Kessler, Ronald C; Mann, J John; Nurnberger, John I; Pistis, Giorgio; Streit, Fabian; Ursano, Robert J; Polimanti, Renato; Dennis, Michelle; Garrett, Melanie; Hair, Lauren; Harvey, Philip; Hauser, Elizabeth R; Hauser, Michael A; Huffman, Jennifer; Jacobson, Daniel; Madduri, Ravi; McMahon, Benjamin; Oslin, David W; Trafton, Jodie; Awasthi, Swapnil; Berrettini, Wade H; Bohus, Martin; Chang, Xiao; Chen, Hsi-Chung; Chen, Wei J; Christensen, Erik D; Crow, Scott; Duriez, Philibert; Edwards, Alexis C; Fernández-Aranda, Fernando; Galfalvy, Hanga; Gandal, Michael; Gorwood, Philip; Guo, Yiran; Hafferty, Jonathan D; Hakonarson, Hakon; Halmi, Katherine A; Hishimoto, Akitoyo; Jain, Sonia; Jamain, Stéphane; Jiménez-Murcia, Susana; Johnson, Craig; Kaplan, Allan S; Kaye, Walter H; Keel, Pamela K; Kennedy, James L; Kim, Minsoo; Klump, Kelly L; Levey, Daniel F; Li, Dong; Liao, Shih-Cheng; Lieb, Klaus; Lilenfeld, Lisa; Marshall, Christian R; Mitchell, James E; Okazaki, Satoshi; Otsuka, Ikuo; Pinto, Dalila; Powers, Abigail; Ramoz, Nicolas; Ripke, Stephan; Roepke, Stefan; Rozanov, Vsevolod; Scherer, Stephen W; Schmahl, Christian; Sokolowski, Marcus; Starnawska, Anna; Strober, Michael; Su, Mei-Hsin; Thornton, Laura M; Treasure, Janet; Ware, Erin B; Watson, Hunna J; Witt, Stephanie H; Woodside, D Blake; Yilmaz, Zeynep; Zillich, Lea; Adolfsson, Rolf; Agartz, Ingrid; Alda, Martin; Alfredsson, Lars; Appadurai, Vivek; Artigas, María Soler; Van der Auwera, Sandra; Azevedo, M Helena; Bass, Nicholas; Bau, Claiton HD; Baune, Bernhard T; Bellivier, Frank; Berger, Klaus; Biernacka, Joanna M; Bigdeli, Tim B; Binder, Elisabeth B; Boehnke, Michael; Boks, Marco P; Braff, David L; Bryant, Richard; Budde, Monika; Byrne, Enda M; Cahn, Wiepke; Castelao, Enrique; Cervilla, Jorge A; Chaumette, Boris; Corvin, Aiden; Craddock, Nicholas; Djurovic, Srdjan; Foo, Jerome C; Forstner, Andreas J; Frye, Mark; Gatt, Justine M; Giegling, Ina; Grabe, Hans J; Green, Melissa J; Grevet, Eugenio H; Grigoroiu-Serbanescu, Maria; Gutierrez, Blanca; Guzman-Parra, Jose; Hamshere, Marian L; Hartmann, Annette M; Hauser, Joanna; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Ising, Marcus; Jones, Ian; Jones, Lisa A; Jonsson, Lina; Kahn, René S; Kelsoe, John R; Kendler, Kenneth S; Kloiber, Stefan; Koenen, Karestan C; Kogevinas, Manolis; Krebs, Marie-Odile; Landén, Mikael; Leboyer, Marion; Lee, Phil H; Levinson, Douglas F; Liao, Calwing; Lissowska, Jolanta; Mayoral, Fermin; McElroy, Susan L; McGrath, Patrick; McGuffin, Peter; McQuillin, Andrew; Mehta, Divya; Melle, Ingrid; Mitchell, Philip B; Molina, Esther; Morken, Gunnar; Nievergelt, Caroline; Nöthen, Markus M; O'Donovan, Michael C; Ophoff, Roel A; Owen, Michael J; Pato, Carlos; Pato, Michele T; Penninx, Brenda WJH; Potash, James B; Power, Robert A; Preisig, Martin; Quested, Digby; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Ribasés, Marta; Richarte, Vanesa; Rietschel, Marcella; Rivera, Margarita; Roberts, Andrea; Roberts, Gloria; Rouleau, Guy A; Rovaris, Diego L; Sanders, Alan R; Schofield, Peter R; Schulze, Thomas G; Scott, Laura J; Serretti, Alessandro; Shi, Jianxin; Sirignano, Lea; Sklar, Pamela; Smeland, Olav B; Smoller, Jordan W; Sonuga-Barke, Edmund JS; Trzaskowski, Maciej; Tsuang, Ming T; Turecki, Gustavo; Vilar-Ribó, Laura; Vincent, John B; Völzke, Henry; Walters, James TR; Weickert, Cynthia Shannon; Weickert, Thomas W; Weissman, Myrna M; Williams, Leanne M; Wray, Naomi R; Zai, Clement C; Agerbo, Esben; Børglum, Anders D; Breen, Gerome; Demontis, Ditte; Erlangsen, Annette; Gelernter, Joel; Glatt, Stephen J; Hougaard, David M; Hwu, Hai-Gwo; Kuo, Po-Hsiu; Lewis, Cathryn M; Li, Qingqin S; Liu, Chih-Min; Martin, Nicholas G; McIntosh, Andrew M; Medland, Sarah E; Mors, Ole; Nordentoft, Merete; Olsen, Catherine M; Porteous, David; Smith, Daniel J; Stahl, Eli A; Stein, Murray B; Wasserman, Danuta; Werge, Thomas; Whiteman, David C; Willour, Virginia; VA Million Veteran Program (MVP); MVP Suicide Exemplar Workgroup; Suicide Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Eating Disorder Working Group of the Psychiatric Genomics Consortium; German Borderline Genomics Consortium; Coon, Hilary; Beckham, Jean C; Kimbrel, Nathan A; Ruderfer, Douglas MObjective
Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.Methods
This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Results
Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.Conclusions
This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.Item Open Access International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.(Nature communications, 2019-10) 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; 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 PF; 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; 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, Ross McD; Young, Keith A; Zhao, Hongyu; Zoellner, Lori A; Liberzon, Israel; Ressler, Kerry J; Haas, Magali; Koenen, Karestan CThe 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.Item Open Access Large epigenome-wide association study identifies multiple novel differentially methylated CpG sites associated with suicidal thoughts and behaviors in veterans.(Frontiers in psychiatry, 2023-01) Kimbrel, Nathan A; Garrett, Melanie E; Evans, Mariah K; Mellows, Clara; Dennis, Michelle F; Hair, Lauren P; Hauser, Michael A; VA Mid-Atlantic MIRECC Workgroup; Ashley-Koch, Allison E; Beckham, Jean CIntroduction
The U.S. suicide mortality rate has steadily increased during the past two decades, particularly among military veterans; however, the epigenetic basis of suicidal thoughts and behaviors (STB) remains largely unknown.Methods
To address this issue, we conducted an epigenome-wide association study of DNA methylation (DNAm) of peripheral blood samples obtained from 2,712 U.S. military veterans.Results
Three DNAm probes were significantly associated with suicide attempts, surpassing the multiple testing threshold (FDR q-value <0.05), including cg13301722 on chromosome 7, which lies between the genes SLC4A2 and CDK5; cg04724646 in PDE3A; and cg04999352 in RARRES3. cg13301722 was also found to be differentially methylated in the cerebral cortex of suicide decedents in a publicly-available dataset (p = 0.03). Trait enrichment analysis revealed that the CpG sites most strongly associated with STB in the present sample were also associated with smoking, alcohol consumption, maternal smoking, and maternal alcohol consumption, whereas pathway enrichment analysis revealed significant associations with circadian rhythm, adherens junction, insulin secretion, and RAP-1 signaling, each of which was recently associated with suicide attempts in a large, independent genome-wide association study of suicide attempts of veterans.Discussion
Taken together, the present findings suggest that SLC4A2, CDK5, PDE3A, and RARRES3 may play a role in STB. CDK5, a member of the cyclin-dependent kinase family that is highly expressed in the brain and essential for learning and memory, appears to be a particularly promising candidate worthy of future study; however, additional work is still needed to replicate these finding in independent samples.Item Open Access Posttraumatic stress disorder, trauma, and accelerated biological aging among post-9/11 veterans.(Translational psychiatry, 2024-01) Bourassa, Kyle J; Garrett, Melanie E; Caspi, Avshalom; Dennis, Michelle; Hall, Katherine S; Moffitt, Terrie E; Taylor, Gregory A; VA Mid Atlantic MIRECC Workgroup; Ashley-Koch, Allison E; Beckham, Jean C; Kimbrel, Nathan APeople who experience trauma and develop posttraumatic stress disorder (PTSD) are at increased risk for poor health. One mechanism that could explain this risk is accelerated biological aging, which is associated with the accumulation of chronic diseases, disability, and premature mortality. Using data from 2309 post-9/11 United States military veterans who participated in the VISN 6 MIRECC's Post-Deployment Mental Health Study, we tested whether PTSD and trauma exposure were associated with accelerated rate of biological aging, assessed using a validated DNA methylation (DNAm) measure of epigenetic aging-DunedinPACE. Veterans with current PTSD were aging faster than those who did not have current PTSD, β = 0.18, 95% CI [0.11, 0.27], p < .001. This effect represented an additional 0.4 months of biological aging each year. Veterans were also aging faster if they reported more PTSD symptoms, β = 0.13, 95% CI [0.09, 0.16], p < 0.001, or higher levels of trauma exposure, β = 0.09, 95% CI [0.05, 0.13], p < 0.001. Notably, veterans with past PTSD were aging more slowly than those with current PTSD, β = -0.21, 95% CI [-0.35, -0.07], p = .003. All reported results accounted for age, gender, self-reported race/ethnicity, and education, and remained when controlling for smoking. Our findings suggest that an accelerated rate of biological aging could help explain how PTSD contributes to poor health and highlights the potential benefits of providing efficacious treatment to populations at increased risk of trauma and PTSD.Item Open Access Probable trauma associated sleep disorder in post-9/11 US Veterans(SLEEP Advances, 2023-01-01) Taylor, Kenneth A; Mysliwiec, Vincent; Kimbrel, Nathan A; Augustine, Ann V; VA Mid-Atlantic MIRECC Registry Workgroup; Ulmer, Christi SAbstractStudy ObjectivesThe purpose of this study was to (1) estimate trauma associated sleep disorder (TASD) prevalence among post-9/11 era veterans and to describe differences in service and comorbid mental health clinical characteristics among individuals with and without probable TASD, and (2) estimate TASD prevalence and characteristics of reported traumatic experiences stratified by sex.MethodsWe used cross-sectional data from the post-deployment mental health study of post-9/11 veterans, which enrolled and collected baseline data from 2005 to 2018. We classified veterans as having probable TASD using self-reported measures: traumatic experiences from the traumatic life events questionnaire (TLEQ) and items from the Pittsburgh sleep quality index with Addendum for posttraumatic stress disorder (PTSD) mapped to TASD diagnostic criteria and ascertained mental health diagnoses (PTSD, major depressive disorder [MDD]) via Structured Clinical Interview for DSM-IV. We calculated effect sizes as prevalence ratios (PR) for categorical variables and Hedges’ g for continuous variables.ResultsOur final sample included 3618 veterans (22.7% female). TASD prevalence was 12.1% (95% CI: 11.1% to 13.2%) and sex-stratified prevalence was similar for female and male veterans. Veterans with TASD had a much higher comorbid prevalence of PTSD (PR: 3.72, 95% CI: 3.41 to 4.06) and MDD (PR: 3.93, 95% CI: 3.48 to 4.43). Combat was the highest reported most distressing traumatic experience among veterans with TASD (62.6%). When stratifying by sex, female veterans with TASD had a wider variety of traumatic experiences.ConclusionsOur results support the need for improved screening and evaluation for TASD in veterans, which is currently not performed in routine clinical practice.Item Open Access The genetic architecture of the human cerebral cortex.(Science (New York, N.Y.), 2020-03) Grasby, Katrina L; Jahanshad, Neda; Painter, Jodie N; Colodro-Conde, Lucía; Bralten, Janita; Hibar, Derrek P; Lind, Penelope A; Pizzagalli, Fabrizio; Ching, Christopher RK; McMahon, Mary Agnes B; Shatokhina, Natalia; Zsembik, Leo CP; Thomopoulos, Sophia I; Zhu, Alyssa H; Strike, Lachlan T; Agartz, Ingrid; Alhusaini, Saud; Almeida, Marcio AA; Alnæs, Dag; Amlien, Inge K; Andersson, Micael; Ard, Tyler; Armstrong, Nicola J; Ashley-Koch, Allison; Atkins, Joshua R; Bernard, Manon; Brouwer, Rachel M; Buimer, Elizabeth EL; Bülow, Robin; Bürger, Christian; Cannon, Dara M; Chakravarty, Mallar; Chen, Qiang; Cheung, Joshua W; Couvy-Duchesne, Baptiste; Dale, Anders M; Dalvie, Shareefa; de Araujo, Tânia K; de Zubicaray, Greig I; de Zwarte, Sonja MC; den Braber, Anouk; Doan, Nhat Trung; Dohm, Katharina; Ehrlich, Stefan; Engelbrecht, Hannah-Ruth; Erk, Susanne; Fan, Chun Chieh; Fedko, Iryna O; Foley, Sonya F; Ford, Judith M; Fukunaga, Masaki; Garrett, Melanie E; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Green, Melissa J; Groenewold, Nynke A; Grotegerd, Dominik; Gurholt, Tiril P; Gutman, Boris A; Hansell, Narelle K; Harris, Mathew A; Harrison, Marc B; Haswell, Courtney C; Hauser, Michael; Herms, Stefan; Heslenfeld, Dirk J; Ho, New Fei; Hoehn, David; Hoffmann, Per; Holleran, Laurena; Hoogman, Martine; Hottenga, Jouke-Jan; Ikeda, Masashi; Janowitz, Deborah; Jansen, Iris E; Jia, Tianye; Jockwitz, Christiane; Kanai, Ryota; Karama, Sherif; Kasperaviciute, Dalia; Kaufmann, Tobias; Kelly, Sinead; Kikuchi, Masataka; Klein, Marieke; Knapp, Michael; Knodt, Annchen R; Krämer, Bernd; Lam, Max; Lancaster, Thomas M; Lee, Phil H; Lett, Tristram A; Lewis, Lindsay B; Lopes-Cendes, Iscia; Luciano, Michelle; Macciardi, Fabio; Marquand, Andre F; Mathias, Samuel R; Melzer, Tracy R; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Moreira, Jose CV; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Najt, Pablo; Nakahara, Soichiro; Nho, Kwangsik; Olde Loohuis, Loes M; Orfanos, Dimitri Papadopoulos; Pearson, John F; Pitcher, Toni L; Pütz, Benno; Quidé, Yann; Ragothaman, Anjanibhargavi; Rashid, Faisal M; Reay, William R; Redlich, Ronny; Reinbold, Céline S; Repple, Jonathan; Richard, Geneviève; Riedel, Brandalyn C; Risacher, Shannon L; Rocha, Cristiane S; Mota, Nina Roth; Salminen, Lauren; Saremi, Arvin; Saykin, Andrew J; Schlag, Fenja; Schmaal, Lianne; Schofield, Peter R; Secolin, Rodrigo; Shapland, Chin Yang; Shen, Li; Shin, Jean; Shumskaya, Elena; Sønderby, Ida E; Sprooten, Emma; Tansey, Katherine E; Teumer, Alexander; Thalamuthu, Anbupalam; Tordesillas-Gutiérrez, Diana; Turner, Jessica A; Uhlmann, Anne; Vallerga, Costanza Ludovica; van der Meer, Dennis; van Donkelaar, Marjolein MJ; van Eijk, Liza; van Erp, Theo GM; van Haren, Neeltje EM; van Rooij, Daan; van Tol, Marie-José; Veldink, Jan H; Verhoef, Ellen; Walton, Esther; Wang, Mingyuan; Wang, Yunpeng; Wardlaw, Joanna M; Wen, Wei; Westlye, Lars T; Whelan, Christopher D; Witt, Stephanie H; Wittfeld, Katharina; Wolf, Christiane; Wolfers, Thomas; Wu, Jing Qin; Yasuda, Clarissa L; Zaremba, Dario; Zhang, Zuo; Zwiers, Marcel P; Artiges, Eric; Assareh, Amelia A; Ayesa-Arriola, Rosa; Belger, Aysenil; Brandt, Christine L; Brown, Gregory G; Cichon, Sven; Curran, Joanne E; Davies, Gareth E; Degenhardt, Franziska; Dennis, Michelle F; Dietsche, Bruno; Djurovic, Srdjan; Doherty, Colin P; Espiritu, Ryan; Garijo, Daniel; Gil, Yolanda; Gowland, Penny A; Green, Robert C; Häusler, Alexander N; Heindel, Walter; Ho, Beng-Choon; Hoffmann, Wolfgang U; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Jack, Clifford R; Jang, MiHyun; Jansen, Andreas; Kimbrel, Nathan A; Kolskår, Knut; Koops, Sanne; Krug, Axel; Lim, Kelvin O; Luykx, Jurjen J; Mathalon, Daniel H; Mather, Karen A; Mattay, Venkata S; Matthews, Sarah; Mayoral Van Son, Jaqueline; McEwen, Sarah C; Melle, Ingrid; Morris, Derek W; Mueller, Bryon A; Nauck, Matthias; Nordvik, Jan E; Nöthen, Markus M; O'Leary, Daniel S; Opel, Nils; Martinot, Marie-Laure Paillère; Pike, G Bruce; Preda, Adrian; Quinlan, Erin B; Rasser, Paul E; Ratnakar, Varun; Reppermund, Simone; Steen, Vidar M; Tooney, Paul A; Torres, Fábio R; Veltman, Dick J; Voyvodic, James T; Whelan, Robert; White, Tonya; Yamamori, Hidenaga; Adams, Hieab HH; Bis, Joshua C; Debette, Stephanie; Decarli, Charles; Fornage, Myriam; Gudnason, Vilmundur; Hofer, Edith; Ikram, M Arfan; Launer, Lenore; Longstreth, WT; Lopez, Oscar L; Mazoyer, Bernard; Mosley, Thomas H; Roshchupkin, Gennady V; Satizabal, Claudia L; Schmidt, Reinhold; Seshadri, Sudha; Yang, Qiong; Alzheimer’s Disease Neuroimaging Initiative; CHARGE Consortium; EPIGEN Consortium; IMAGEN Consortium; SYS Consortium; Parkinson’s Progression Markers Initiative; Alvim, Marina KM; Ames, David; Anderson, Tim J; Andreassen, Ole A; Arias-Vasquez, Alejandro; Bastin, Mark E; Baune, Bernhard T; Beckham, Jean C; Blangero, John; Boomsma, Dorret I; Brodaty, Henry; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bustillo, Juan R; Cahn, Wiepke; Cairns, Murray J; Calhoun, Vince; Carr, Vaughan J; Caseras, Xavier; Caspers, Svenja; Cavalleri, Gianpiero L; Cendes, Fernando; Corvin, Aiden; Crespo-Facorro, Benedicto; Dalrymple-Alford, John C; Dannlowski, Udo; de Geus, Eco JC; Deary, Ian J; Delanty, Norman; Depondt, Chantal; Desrivières, Sylvane; Donohoe, Gary; Espeseth, Thomas; Fernández, Guillén; Fisher, Simon E; Flor, Herta; Forstner, Andreas J; Francks, Clyde; Franke, Barbara; Glahn, David C; Gollub, Randy L; Grabe, Hans J; Gruber, Oliver; Håberg, Asta K; Hariri, Ahmad R; Hartman, Catharina A; Hashimoto, Ryota; Heinz, Andreas; Henskens, Frans A; Hillegers, Manon HJ; Hoekstra, Pieter J; Holmes, Avram J; Hong, L Elliot; Hopkins, William D; Hulshoff Pol, Hilleke E; Jernigan, Terry L; Jönsson, Erik G; Kahn, René S; Kennedy, Martin A; Kircher, Tilo TJ; Kochunov, Peter; Kwok, John BJ; Le Hellard, Stephanie; Loughland, Carmel M; Martin, Nicholas G; Martinot, Jean-Luc; McDonald, Colm; McMahon, Katie L; Meyer-Lindenberg, Andreas; Michie, Patricia T; Morey, Rajendra A; Mowry, Bryan; Nyberg, Lars; Oosterlaan, Jaap; Ophoff, Roel A; Pantelis, Christos; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Polderman, Tinca JC; Posthuma, Danielle; Rietschel, Marcella; Roffman, Joshua L; Rowland, Laura M; Sachdev, Perminder S; Sämann, Philipp G; Schall, Ulrich; Schumann, Gunter; Scott, Rodney J; Sim, Kang; Sisodiya, Sanjay M; Smoller, Jordan W; Sommer, Iris E; St Pourcain, Beate; Stein, Dan J; Toga, Arthur W; Trollor, Julian N; Van der Wee, Nic JA; van 't Ent, Dennis; Völzke, Henry; Walter, Henrik; Weber, Bernd; Weinberger, Daniel R; Wright, Margaret J; Zhou, Juan; Stein, Jason L; Thompson, Paul M; Medland, Sarah E; Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working groupThe cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.