Dataset Information

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

ABSTRACT:

Background

Posttraumatic 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).

Methods

A 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.

Results

GWASs 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.

Conclusions

Through 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.

SUBMITTER: Maihofer AX

PROVIDER: S-EPMC8917986 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Maihofer Adam X AX Choi Karmel W KW Coleman Jonathan R I JRI Daskalakis Nikolaos P NP Denckla Christy A CA Ketema Elizabeth E Morey Rajendra A RA Polimanti Renato R Ratanatharathorn Andrew A Torres Katy K Wingo Aliza P AP Zai Clement C CC Aiello Allison E AE Almli Lynn M LM Amstadter Ananda B AB Andersen Soren B SB Andreassen Ole A OA Arbisi Paul A PA Ashley-Koch Allison E AE Austin S Bryn SB Avdibegović Esmina E Borglum Anders D AD Babić Dragan D Bækvad-Hansen Marie M Baker Dewleen G DG Beckham Jean C JC Bierut Laura J LJ Bisson Jonathan I JI Boks Marco P MP Bolger Elizabeth A EA Bradley Bekh B Brashear Meghan M Breen Gerome G Bryant Richard A RA Bustamante Angela C AC Bybjerg-Grauholm Jonas J Calabrese Joseph R JR Caldas-de-Almeida José M JM Chen Chia-Yen CY Dale Anders M AM Dalvie Shareefa S Deckert Jürgen J Delahanty Douglas L DL Dennis Michelle F MF Disner Seth G SG Domschke Katharina K Duncan Laramie E LE Džubur Kulenović Alma A Erbes Christopher R CR Evans Alexandra A Farrer Lindsay A LA Feeny Norah C NC Flory Janine D JD Forbes David D Franz Carol E CE Galea Sandro S Garrett Melanie E ME Gautam Aarti A Gelaye Bizu B Gelernter Joel J Geuze Elbert E Gillespie Charles F CF Goçi Aferdita A Gordon Scott D SD Guffanti Guia G Hammamieh Rasha R Hauser Michael A MA Heath Andrew C AC Hemmings Sian M J SMJ Hougaard David Michael DM Jakovljević Miro M Jett Marti M Johnson Eric Otto EO Jones Ian I Jovanovic Tanja T Qin Xue-Jun XJ Karstoft Karen-Inge KI Kaufman Milissa L ML Kessler Ronald C RC Khan Alaptagin A Kimbrel Nathan A NA King Anthony P AP Koen Nastassja N Kranzler Henry R HR Kremen William S WS Lawford Bruce R BR Lebois Lauren A M LAM Lewis Catrin C Liberzon Israel I Linnstaedt Sarah D SD Logue Mark W MW Lori Adriana A Lugonja Božo B Luykx Jurjen J JJ Lyons Michael J MJ Maples-Keller Jessica L JL Marmar Charles C Martin Nicholas G NG Maurer Douglas D Mavissakalian Matig R MR McFarlane Alexander A McGlinchey Regina E RE McLaughlin Katie A KA McLean Samuel A SA Mehta Divya D Mellor Rebecca R Michopoulos Vasiliki V Milberg William W Miller Mark W MW Morris Charles Phillip CP Mors Ole O Mortensen Preben B PB Nelson Elliot C EC Nordentoft Merete M Norman Sonya B SB O'Donnell Meaghan M Orcutt Holly K HK Panizzon Matthew S MS Peters Edward S ES Peterson Alan L AL Peverill Matthew M Pietrzak Robert H RH Polusny Melissa A MA Rice John P JP Risbrough Victoria B VB Roberts Andrea L AL Rothbaum Alex O AO Rothbaum Barbara O BO Roy-Byrne Peter P Ruggiero Kenneth J KJ Rung Ariane A Rutten Bart P F BPF Saccone Nancy L NL Sanchez Sixto E SE Schijven Dick D Seedat Soraya S Seligowski Antonia V AV Seng Julia S JS Sheerin Christina M CM Silove Derrick D Smith Alicia K AK Smoller Jordan W JW Sponheim Scott R SR Stein Dan J DJ Stevens Jennifer S JS Teicher Martin H MH Thompson Wesley K WK Trapido Edward E Uddin Monica M Ursano Robert J RJ van den Heuvel Leigh Luella LL Van Hooff Miranda M Vermetten Eric E Vinkers Christiaan H CH Voisey Joanne J Wang Yunpeng Y Wang Zhewu Z Werge Thomas T Williams Michelle A MA Williamson Douglas E DE Winternitz Sherry S Wolf Christiane C Wolf Erika J EJ Yehuda Rachel R Young Keith A KA Young Ross McD RM Zhao Hongyu H Zoellner Lori A LA Haas Magali M Lasseter Heather H Provost Allison C AC Salem Rany M RM Sebat Jonathan J Shaffer Richard A RA Wu Tianying T Ripke Stephan S Daly Mark J MJ Ressler Kerry J KJ Koenen Karestan C KC Stein Murray B MB Nievergelt Caroline M CM

Biological psychiatry 20210928 7

<h4>Background</h4>Posttraumatic 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).<h4>Methods</h4>A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry partic ...[more]

PMID: 34865855

Similar Datasets

Project description:ImportancePhysicians are exposed to traumatic events during their work, but the impact and outcomes of these exposures are understudied.ObjectiveTo determine the prevalence and associations of work-related trauma exposure and posttraumatic stress disorder (PTSD) among a cohort of resident physicians in their internship year of training.Design, setting, and participantsThis cohort study involved physicians entering internship at US residency programs nationwide in 2018. Participants completed a baseline survey 1 to 2 months before commencing internship, as well as follow-up surveys at 4 time points during internship. Statistical analysis was performed from April 2020 to January 2021.ExposuresTwelve months of internship.Main outcomes and measuresPrevalence of work-related trauma and prevalence of PTSD among those who experienced work-related trauma. Trauma exposure and PTSD symptoms were assessed using the Primary Care PTSD Screen for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PC-PTSD-5). Risk factors assessed included depression, anxiety, early family environment, stressful life experiences, medical specialty, hours worked, and concern about medical errors.ResultsAmong 1134 interns who completed the PC-PTSD-5 at month 12 of internship, 665 (58.6%) were female and 695 (61.6%) were non-Hispanic White; the mean (SD) age was 27.52 (2.50) years. There were 640 interns (56.4%) who reported work-related trauma exposure; among these interns with trauma exposure, 123 (19.0%) screened positive for PTSD. Overall, 123 of 1134 training physicians (10.8%) screened positive for PTSD by the end of internship year, as compared with a 12-month PTSD prevalence rate of 3.6% in the general population. Multivariable logistic regression analyses, adjusting for demographic characteristics, indicated that risk factors associated with trauma exposure included non-Hispanic White race/ethnicity (odds ratio [OR], 1.51 [95% CI, 1.14-2.01]; P = .004), more hours worked (OR, 1.01 [95% CI, 1.00-1.03]; P = .03), early family environment (OR, 1.03 [95% CI, 1.01-1.05]; P < .001), and stressful life experiences at baseline (OR, 1.46 [95% CI, 1.06-2.01]; P = .02). Risk factors associated with PTSD were being unmarried (OR, 2.00 [95% CI, 1.07-3.73]; P = .03) and non-Hispanic White (OR, 1.77 [95% CI, 1.01-3.11]; P = .05), concern about medical errors (OR, 1.21 [95% CI, 1.00-1.46]; P = .05), stressful life experiences during internship (OR, 1.43 [95% CI, 1.14-1.81]; P = .002), depression at month 12 of internship (OR, 2.52 [95% CI = 1.36-4.65], P = .003), and anxiety at month 12 of internship (OR, 2.14, [95% CI, 1.13-4.04]; P = .02).Conclusions and relevanceThis study found that work-related PTSD was 3 times more prevalent among intern physicians than the general population. These findings suggest that effective interventions to reduce trauma exposure and mitigate the effects of trauma are needed.

Project description:Posttraumatic stress disorder (PTSD) appears to increase obesity risk but the pathways by which PTSD leads to weight gain are not known. Identification of the links between PTSD and obesogenic eating behaviors is necessary to clarify this pathway and inform development of obesity prevention strategies in PTSD-affected populations.To determine whether women with PTSD symptoms are more likely to report food addiction, a measure of perceived dependence on food, than women without PTSD symptoms. Also, to determine whether age at PTSD symptom onset and type of trauma influence the PTSD-food addiction association.Cross-sectional analysis of 49,408 participants in the Nurses' Health Study II, a cohort comprising women nurses who were aged 25 to 42 years at the 1989 recruitment from 14 US states.The Nurses' Health Study II ascertained lifetime trauma exposure and PTSD symptoms in 2008 and current food addiction in 2009. Food addiction was defined as 3 or more clinically significant symptoms on a modified version of the Yale Food Addiction Scale. Confounder-adjusted prevalence ratios and 95% CIs were estimated using modified Poisson regression.Approximately 80% of the study sample reported some type of trauma exposure, with 66% of the trauma-exposed participants reporting at least 1 lifetime PTSD symptom. Eight percent of the cohort met the criteria for food addiction. The prevalence of food addiction increased with the number of lifetime PTSD symptoms, and women with the greatest number of PTSD symptoms (6-7 symptoms) had more than twice the prevalence of food addiction as women with neither PTSD symptoms nor trauma histories (prevalence ratio, 2.68; 95% CI, 2.41-2.97). Symptoms of PTSD were more strongly related to food addiction when symptom onset occurred at an earlier age. The PTSD-food addiction association did not differ substantially by trauma type.Symptoms of PTSD were associated with increased food addiction prevalence in this cohort of women. Strategies to reduce obesity associated with PTSD may require psychological and behavioral interventions that address dependence on food and/or use of food to cope with distress.

Project description:BackgroundPosttraumatic stress disorder (PTSD) is a debilitating anxiety disorder. Surveys of the general population suggest that while 50-85% of Americans will experience a traumatic event in their lifetime, only 2-50% will develop PTSD. Why some individuals develop PTSD following trauma exposure while others remain resilient is a central question in the field of trauma research. For more than half a century, the role of genetic influences on PTSD has been considered as a potential vulnerability factor. However, despite the exponential growth of molecular genetic studies over the past decade, limited progress has been made in identifying true genetic variants for PTSD.MethodsIn an attempt to aid future genome wide association studies (GWAS), this paper presents a systematic review of 28 genetic association studies of PTSD. Inclusion criteria required that 1) all participants were exposed to Criterion A traumatic events, 2) polymorphisms of relevant genes were genotyped and assessed in relation to participants' PTSD status, 3) quantitative methods were used, and 4) articles were published in English and in peer-reviewed journals. In the examination of these 28 studies, particular attention was given to variables related to trauma exposure (e.g. number of traumas, type of trauma).ResultsResults indicated that most articles did not report on the GxE interaction in the context of PTSD or present data on the main effects of E despite having data available. Furthermore, some studies that did consider the GxE interaction had significant findings, underscoring the importance of examining how genotypes can modify the effect of trauma on PTSD. Additionally, results indicated that only a small number of genes continue to be studied and that there were marked differences in methodologies across studies, which subsequently limited robust conclusions.ConclusionsAs trauma exposure is a necessary condition for the PTSD diagnosis, this paper identifies gaps in the current literature as well as provides recommendations for how future GWAS studies can most effectively incorporate trauma exposure data in both the design and analysis phases of studies.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets