Genome-wide linkage and association analyses implicate FASN in predisposition to Uterine Leiomyomata.

Uterine leiomyomata (UL), the most prevalent pelvic tumors in women of reproductive age, pose a major public health problem given their high frequency, associated morbidities, and most common indication for hysterectomies. A genetic component to UL predisposition is supported by analyses of ethnic predisposition, twin studies, and familial aggregation. A genome-wide SNP linkage panel was genotyped and analyzed in 261 white UL-affected sister-pair families from the Finding Genes for Fibroids study. Two significant linkage regions were detected in 10p11 (LOD = 4.15) and 3p21 (LOD = 3.73), and five additional linkage regions were identified with LOD scores > 2.00 in 2q37, 5p13, 11p15, 12q14, and 17q25. Genome-wide association studies were performed in two independent cohorts of white women, and a meta-analysis was conducted. One SNP (rs4247357) was identified with a p value (p = 3.05 × 10(-8)) that reached genome-wide significance (odds ratio = 1.299). The candidate SNP is under a linkage peak and in a block of linkage disequilibrium in 17q25.3, which spans fatty acid synthase (FASN), coiled-coil-domain-containing 57 (CCDC57), and solute-carrier family 16, member 3 (SLC16A3). By tissue microarray immunohistochemistry, we found elevated (3-fold) FAS levels in UL-affected tissue compared to matched myometrial tissue. FAS transcripts and/or protein levels are upregulated in various neoplasms and implicated in tumor cell survival. FASN represents the initial UL risk allele identified in white women by a genome-wide, unbiased approach and opens a path to management and potential therapeutic intervention.

No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis.

STUDY QUESTION: Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk? SUMMARY ANSWER: We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS. WHAT IS KNOWN ALREADY: The rs61764370 SNP in the 3' untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis. STUDY DESIGN, SIZE AND DURATION: This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS: We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform. MAIN RESULTS AND THE ROLE OF CHANCE: There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk. LIMITATIONS AND REASONS FOR CAUTION: The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk. STUDY FUNDING/COMPETING INTEREST(S): The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

Traumatic events, other operational stressors and physical and mental health reported by Australian Defence Force personnel following peacekeeping and war-like deployments.

BACKGROUND: The association between stressful events on warlike deployments and subsequent mental health problems has been established. Less is known about the effects of stressful events on peacekeeping deployments. METHODS: Two cross sectional studies of the Australian Defence Force were used to contrast the prevalence of exposures reported by a group deployed on a peacekeeping operation (Bougainville, n = 1704) and those reported by a group deployed on operations which included warlike and non-warlike exposures (East Timor, n = 1333). A principal components analysis was used to identify groupings of non-traumatic exposures on deployment. Multiple regression models were used to assess the association between self-reported objective and subjective exposures, stressors on deployment and subsequent physical and mental health outcomes. RESULTS: The principal components analysis produced four groups of non-traumatic stressors which were consistent between the peacekeeping and more warlike deployments. These were labelled 'separation', 'different culture', 'other people' and 'work frustration'. Higher levels of traumatic and non-traumatic exposures were reported by veterans of East Timor compared to Bougainville. Higher levels of subjective traumatic exposures were associated with increased rates of PTSD in East Timor veterans and more physical and psychological health symptoms in both deployed groups. In Bougainville and East Timor veterans some non-traumatic deployment stressors were also associated with worse health outcomes. CONCLUSION: Strategies to best prepare, identify and treat those exposed to traumatic events and other stressors on deployment should be considered for Defence personnel deployed on both warlike and peacekeeping operations.

Comparison of self-reported and audiometrically-measured hearing loss in the Australian Defence Force.

OBJECTIVE: To investigate the relationship between self-reported and audiometrically-measured hearing loss in a sample of Australian Defence Force personnel. DESIGN: Responses to a question regarding hearing problems were compared with contemporaneous audiometric data. STUDY SAMPLE: 3335 members of the Australian Defence Force for whom anonymised medical records were available. RESULTS: The sensitivity of self-report data to identify higher-frequency hearing loss was lower than sensitivity at other frequencies, and positive predictive values were moderate to poor at all frequencies. Performance characteristics of self-report compared with audiometric data also varied with age, sex, and rank. CONCLUSIONS: While self-report hearing loss data have good performance characteristics for estimating prevalence of hearing loss as defined by audiometric criteria, this study indicates that the usefulness of self-report data in identifying individuals with hearing loss may be limited in this population.

Evaluation of polymorphisms in predicted target sites for micro RNAs differentially expressed in endometriosis.

Previous microarray analyses identified 22 microRNAs (miRNAs) differentially expressed in paired ectopic and eutopic endometrium of women with and without endometriosis. To investigate further the role of these miRNAs in women with endometriosis, we conducted an association study aiming to explore the relationship between endometriosis risk and single-nucleotide polymorphisms (SNPs) in miRNA target sites for these differentially expressed miRNAs. A panel of 102 SNPs in the predicted miRNA binding sites were evaluated for an endometriosis association study and an ingenuity pathway analysis was performed. Fourteen rare variants were identified in this study. We found SNP rs14647 in the Wolf-Hirschhorn syndrome candidate gene1 (WHSC1) 3'UTR (untranslated region) was associated with endometriosis-related infertility presenting an odds ratio of 12.2 (95% confidence interval = 2.4-60.7, P = 9.03 × 10(-5)). SNP haplotype AGG in the solute carrier family 22, member 23 (SLC22A23) 3'UTR was associated with endometriosis-related infertility and more severe disease. With the individual genotyping data, ingenuity pathways analysis identified the tumour necrosis factor and cyclin-dependant kinase inhibitor as major factors in the molecular pathways. Significant associations between WHSC1 alleles and endometriosis-related infertility and SLC22A23 haplotypes and the disease severe stage were identified. These findings may help focus future research on subphenotypes of this disease. Replication studies in independent large sample sets to confirm and characterize the involvement of the gene variation in the pathogenesis of endometriosis are needed.

Self-reported tinnitus and ototoxic exposures among deployed Australian Defence Force personnel.

The objective of this study was to investigate the effect of chemical and environmental exposures during deployment on tinnitus among Australian Defence Force personnel previously deployed to Bougainville and East Timor. Participants were asked to self-report recent occurrence and severity of "ringing in the ears," and identify any chemical and environmental exposures during their deployment. Self-reported exposure to loud noises, heavy metals, intense smoke, engine exhaust, solvents and degreasing agents, and chemical spills increased the risk of self-assessed moderate or severe tinnitus. Daily exposure to 4 or more ototoxic factors was associated with 2- to 4-fold increase in the risk. In addition to loud noises, chemical exposures may also play a role in the development of tinnitus among Australian Defence Force personnel serving overseas.

Common genetic influences underlie comorbidity of migraine and endometriosis.

We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12-2.21, P=0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (r(G) = 0.27, 95% CI: 0.06-0.47) and bivariate heritability (h(2)=0.17, 95% CI: 0.08-0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes.

Early menstrual characteristics associated with subsequent diagnosis of endometriosis.

OBJECTIVE: The aim of this study was to investigate the association between early menstrual characteristics, before symptom onset, and later diagnosis of endometriosis. STUDY DESIGN: This was a case-control study of 268 Australian women with surgically confirmed moderate-to-severe endometriosis (cases) and 244 women without endometriosis (controls). Early menstrual cycle characteristics, before age at symptom onset, were analyzed. RESULTS: Menarche after age 14 years was strongly and inversely associated with endometriosis (odds ratio, 0.3; 95% confidence interval, 0.1-0.6). A history of dysmenorrhea was associated with subsequent endometriosis (odds ratio, 2.6; 95% confidence interval, 1.1-6.2). Despite a suggestive trend, shorter menstrual cycle length was not associated with endometriosis. Duration of natural menstruation and heaviness of flow were not associated with subsequent risk of endometriosis; neither was the reported type of sanitary protection used nor history of sexual intercourse during menstruation. CONCLUSION: There is a decreased risk of endometriosis with late age at menarche and an increased risk in women who report an early history of dysmenorrhea.

Smoking prevalence, its determinants and short-term health implications in the Australian Defence Force.

The objectives of this study were to determine the prevalence of smoking, identify the effects of deployment on smoking behavior and risk factors for smoking, and determine the short-term health outcomes associated with smoking in Australian Defence Force (ADF) personnel. Participants were randomly sampled from ADF members who deployed to the Solomon Islands between 2003 and 2005 and from a nondeployed comparison group. In total, 435 of 995 (44%) eligible individuals completed the study questionnaires. The prevalence of current smoking was highest in those who had completed less formal education and those who served in the Navy. Nearly two-thirds (63%) of current or former smokers smoked more while on overseas deployment. Current smokers were more likely to report current wheeze, shortness of breath, and persistent cough compared with nonsmokers. The ADF should continue to address cigarette smoking through its health promotion and health review programs and implement activities to reduce cigarette smoking on deployment.

Genetic influences on handedness: data from 25,732 Australian and Dutch twin families.

Handedness refers to a consistent asymmetry in skill or preferential use between the hands and is related to lateralization within the brain of other functions such as language. Previous twin studies of handedness have yielded inconsistent results resulting from a general lack of statistical power to find significant effects. Here we present analyses from a large international collaborative study of handedness (assessed by writing/drawing or self report) in Australian and Dutch twins and their siblings (54,270 individuals from 25,732 families). Maximum likelihood analyses incorporating the effects of known covariates (sex, year of birth and birth weight) revealed no evidence of hormonal transfer, mirror imaging or twin specific effects. There were also no differences in prevalence between zygosity groups or between twins and their singleton siblings. Consistent with previous meta-analyses, additive genetic effects accounted for about a quarter (23.64%) of the variance (95%CI 20.17, 27.09%) with the remainder accounted for by non-shared environmental influences. The implications of these findings for handedness both as a primary phenotype and as a covariate in linkage and association analyses are discussed.

Verification of consumers' experiences and perceptions of genetic discrimination and its impact on utilization of genetic testing.

PURPOSE: To undertake a systematic process of verification of consumer accounts of alleged genetic discrimination. METHODS: Verification of incidents reported in life insurance and other contexts that met the criteria of genetic discrimination, and the impact of fear of such treatment, was determined, with consent, through interview, document analysis and where appropriate, direct contact with the third party involved. The process comprised obtaining evidence that the alleged incident was accurately reported and determining whether the decision or action seemed to be justifiable and/or ethical. RESULTS: Reported incidents of genetic discrimination were verified in life insurance access, underwriting and coercion (9), applications for worker's compensation (1) and early release from prison (1) and in two cases of fear of discrimination impacting on access to genetic testing. Relevant conditions were inherited cancer susceptibility (8), Huntington disease (3), hereditary hemochromatosis (1), and polycystic kidney disease (1). In two cases, the reversal of an adverse underwriting decision to standard rate after intervention with insurers by genetics health professionals was verified. The mismatch between consumer and third party accounts in three life insurance incidents involved miscommunication or lack of information provision by financial advisers. CONCLUSION: These first cases of verified genetic discrimination make it essential for policies and guidelines to be developed and implemented to ensure appropriate use of genetic test results in insurance underwriting, to promote education and training in the financial industry, and to provide support for consumers and health professionals undertaking challenges of adverse decisions.

An examination of the overlap between genetic and environmental risk factors for intentional weight loss and overeating.

OBJECTIVE: To further our understanding of how intentional weight loss (IWL) and overeating are related, we examined the shared genetic and environmental variance between lifetime IWL and overeating. METHOD: Interview data were available for 1,976 female twins (both members of 439 and 264 pairs of monozygotic and dizygotic twins, respectively), mean age = 40.61, SD = 4.72. We used lifetime diagnostic data for eating disorders obtained from a semistructured psychiatric telephone interview, examined in a bivariate twin analysis. Both lifetime behaviors were measured on a 3-point scale, where absence of IWL or overeating formed one anchor on the scale and lifetime anorexia nervosa (AN) and bulimia nervosa (BN) formed the opposite anchors, respectively. RESULTS: In line with previous findings, a higher body mass index was significantly associated with the lifetime presence of IWL and/or overeating (odds ratio = 1.13, 95% confidence interval (CI): 1.08-1.19). The best fitting twin model contained additive genetic and nonshared environmental influence influencing both IWL and overeating, with correlations between these influences of 0.61 (95% CI: 0.35-0.92) and 0.24 (95% CI: 0.07-0.42), respectively. DISCUSSION: About 37% of genetic risk factors were considered to overlap between IWL and overeating, and with only 6% of overlap between environmental risk factors. Thus, considerable independence of risk factors was indicated.

A genome-wide linkage scan for age at menarche in three populations of European descent.

CONTEXT: Age at menarche (AAM) is an important trait both biologically and socially, a clearly defined event in female pubertal development, and has been associated with many clinically significant phenotypes. OBJECTIVE: The objective of the study was to identify genetic loci influencing variation in AAM in large population-based samples from three countries. DESIGN/PARTICIPANTS: Recalled AAM data were collected from 13,697 individuals and 4,899 pseudoindependent sister-pairs from three different populations (Australia, The Netherlands, and the United Kingdom) by mailed questionnaire or interview. Genome-wide variance components linkage analysis was implemented on each sample individually and in combination. RESULTS: The mean, sd, and heritability of AAM across the three samples was 13.1 yr, 1.5 yr, and 0.69, respectively. No loci were detected that reached genome-wide significance in the combined analysis, but a suggestive locus was detected on chromosome 12 (logarithm of the odds = 2.0). Three loci of suggestive significance were seen in the U.K. sample on chromosomes 1, 4, and 18 (logarithm of the odds = 2.4, 2.2 and 3.2, respectively). CONCLUSIONS: There was no evidence for common highly penetrant variants influencing AAM. Linkage and association suggest that one trait locus for AAM is located on chromosome 12, but further studies are required to replicate these results.

Polymorphisms in the vascular endothelial growth factor gene and the risk of familial endometriosis.

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic protein suspected to be involved in the pathogenesis of endometriosis by establishing a new blood supply to the human exfoliated endometrium. Several transcription factor-binding sites are found in the VEGF 5'-untranslated region and variation within the region increases the transcriptional activity. Six previous studies which tested between one and three single nucleotide polymorphisms (SNPs) in samples comprising 105-215 cases and 100-219 controls have produced conflicting evidence for association between the SNPs in the VEGF region and endometriosis. To further investigate the reported association between VEGF variants and endometriosis, we tested the four VEGF polymorphisms (-2578 A/C, rs699947; -460 T/C, rs833061; +405 G/C, rs2010963 and +936 C/T, rs3025039) in a large Australian sample of 958 familial endometriosis cases and 959 controls. We also conducted a literature-based review of all relevant association studies of these VEGF SNPs in endometriosis and performed a meta-analysis. There was no evidence for association between endometriosis and the VEGF polymorphisms genotyped in our study. Combined association results from a meta-analysis did not provide any evidence for either genotypic or allelic association with endometriosis. Our detailed review and meta-analysis of the VEGF polymorphisms suggests that genotyping assay problems may underlie the previously reported associations between VEGF variants and endometriosis.

Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk.

BACKGROUND: Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8-10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS: We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS: We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS: Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample.

The Deployment Health Surveillance Program: vision and challenges of health surveillance for Australian military cohorts.

The Australian Government has supported the establishment of a Deployment Health Surveillance Program for the Australian Defence Force. Although some health screening mechanisms already exist for Australian Defence Force personnel, until now health data have been used largely for clinical management at an individual level and have not been aggregated to identify trends in health and risk factors in the shorter or longer term. We identify challenges for and potential benefits of health surveillance in the military context, describe features of the Program and progress to date. Retrospective and cross-sectional projects based on deployments to the Near North Area of Influence since 1997 are under way. A planned prospective model of health surveillance for those deploying to the Middle East promises more timely attention to any emerging health problems for military personnel and veterans.

Mammographic density and candidate gene variants: a twins and sisters study.

BACKGROUND: Mammographic density, the light/white radiographic appearance on a mammogram that represents connective and epithelial tissue, is a strong risk factor for breast cancer which seems to be highly heritable. Little is known about its genetic determinants. METHODS: We studied 457 women from 207 sisterhoods (104 monozygotic twins, 182 dizygotic twins, and 171 singletons). Percentage mammographic density (PMD) as well as dense area and nondense area were calculated using a computer-assisted method. We measured six single nucleotide polymorphisms from six candidate genes (COMT, HSD3B1, IGFBP3, HER2, XPD, and XRCC3). Associations between genotypes and mammographic measures were tested (a) cross-sectionally using a multivariate normal model fitted using FISHER that allowed separate correlations for monozygotic, dizygotic, and nontwin pairs and (b) within sister pairs using paired t tests. RESULTS: Cross-sectionally, each additional copy of the HSD3B1 Asn(367)Thr variant allele was associated with lower PMD (-3.47% per allele; SE = 1.65; P = 0.035). Within-pair regression estimates confirmed this association. There was no evidence for an association between the mammographic density measures and any of the other variants studied. CONCLUSION: We have replicated an association between a variant in the HSD3B1 gene and PMD, which suggests that HSD3B1 may be genetic determinant of mammographic density.

Why do they do it? A pilot study towards understanding participant motivation and experience in a large genetic epidemiological study of endometriosis.

OBJECTIVE: This exploratory, pilot study aimed to investigate motivations and reflections of participants who had provided epidemiological information, blood samples and access to clinical records and data in a large genetic epidemiological study of endometriosis, a common multifactorial disorder affecting women. We also aimed to explore understanding of complex genetic or multifactorial conditions in general. METHODS: In-depth interviews were conducted with 16 endometriosis study participants with diverse characteristics. RESULTS: Interviewees generally described their participation in the genetic study using altruistic frameworks of reference. Themes that emerged included unquestioning willingness and consent to participate, little concern about privacy issues, desire for more information from the researchers about the condition rather than scientific progress, the benefits of research participation to family communication, and differing ideas about genetic influences on endometriosis. Specific features of endometriosis also influenced reflections on research participation experience. CONCLUSIONS: As increasing numbers of individuals and families in the community become involved in genetic epidemiological studies of common diseases, more extensive research will be needed to better understand their expectations with a view to improving researchers' communications with study participants.

Australian Twin Registry: a nationally funded resource for medical and scientific research, incorporating match and WATCH.

The Australian Twin Registry (ATR) has, since the late 1970s, enrolled more than 30,000 pairs of all zygosity types and ages willing to consider participation in approved research studies. Its core functions are the recruitment to, and maintenance of, an up-to-date database containing contact details and baseline information, and the management of fair and equitable access so as to enhance medical and scientific research. The ATR has facilitated more than 430 studies producing 525 peer-reviewed publications using a variety of designs including classic biometrical twin and twin family studies, co-twin control studies, intervention studies, longitudinal studies, and studies of issues relevant specifically to twins. The ATR is supported for 2004 to 2009 by an Australian National Health and Medical Research Council (NHMRC) Enabling Grant, a new form of funding which recognizes the importance of long-term support for shared national resources. New initiatives include: integration with the Western Australian Twin Child Health (WATCH) cohort and the new Western Australian Twin Registry (WATR); foundation of a cohort of mothers and their twin children recruited from the time of diagnosis of the multiple gestation (match); a national Twins Festival run in collaboration with the Australian Multiple Birth Association (AMBA); promotion of the ATR at medical conferences; and fostering an active network of researchers from a range of disciplines and providing financial support for new researchers to attend international twin research workshops. Consistent with its mission statement, the long-term goal of the ATR is to make twin studies a standard component of medical and scientific research.

Childhood adversity and traumatic exposures during deployment as predictors of mental health in Australian military veterans.

OBJECTIVE: To examine whether the relationship between traumatic exposure on deployment and poor mental health varies by the reported level of childhood adversity experienced in Australian military veterans deployed to the Bougainville or East Timor military operations. METHODS: Cross-sectional self-reported survey data were collected in 2008 from 3,564 Australian military veterans who deployed to East Timor or Bougainville on their deployment experiences, health and recall of childhood events. Multivariable logistic regression was used to investigate the association between childhood adversity, deployment exposures and mental health. RESULTS: The most common childhood adversity reported was 'not having a special teacher, youth worker or family friend who looked out for them while growing up'. On average, responders reported experiencing 3.5 adverse childhood experiences (SD 2.7) and averaged 5.3 (SD 4.9) traumatic exposures on deployment. Both childhood adversity and traumatic exposures on deployment were associated with higher odds of poorer mental health. However, there was no evidence that level of childhood adversity modified the association between traumatic exposure and mental health. CONCLUSIONS/IMPLICATIONS: These findings suggest that military personnel who recalled a higher level of childhood adversity may need to be monitored for poor mental health and, if required, provided with appropriate support.