The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis.

Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis.

Endometriosis is a common chronic inflammatory condition causing pelvic pain and infertility in women, with limited treatment options and 50% heritability. We leveraged genetic analyses in two species with spontaneous endometriosis, humans and the rhesus macaque, to uncover treatment targets. We sequenced DNA from 32 human families contributing to a genetic linkage signal on chromosome 7p13-15 and observed significant overrepresentation of predicted deleterious low-frequency coding variants in , the gene encoding neuropeptide S receptor 1, in cases (predominantly stage III/IV) versus controls ( = 7.

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.

Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis.

Objective: To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease.

Design: Case-control study.

Setting: Academic research.

Explaining variance in the cumulus mammographic measures that predict breast cancer risk: a twins and sisters study.

Background: Mammographic density, the area of the mammographic image that appears white or bright, predicts breast cancer risk. We estimated the proportions of variance explained by questionnaire-measured breast cancer risk factors and by unmeasured residual familial factors.

Methods: For 544 MZ and 339 DZ twin pairs and 1,558 non-twin sisters from 1,564 families, mammographic density was measured using the computer-assisted method Cumulus.

Genome-wide association meta-analysis identifies new endometriosis risk loci.

We conducted a genome-wide association meta-analysis of 4,604 endometriosis cases and 9,393 controls of Japanese and European ancestry. We show that rs12700667 on chromosome 7p15.2, previously found to associate with disease in Europeans, replicates in Japanese (P = 3.

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.

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.

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).

Does government subsidy for costs of medical and pharmaceutical services result in higher service utilization by older widowed women in Australia?

Background: In Australia, Medicare, the national health insurance system which includes the Medical Benefits Scheme (MBS) and Pharmaceutical Benefits Scheme (PBS), provides partial coverage for most medical services and pharmaceuticals. For war widows, the Department of Veterans' Affairs (DVA) covers almost the entire cost of their health care. The objective of this study was to test whether war widows have higher usage of medical services and pharmaceuticals.

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.

The association between mammographic density measures and aspirin or other NSAID use.

There is evidence that aspirin use reduces the risk of breast cancer. Increased mammographic density is known to be associated with increased breast cancer risk. Little is known about the association between mammographic density and aspirin or other non-steroidal anti-inflammatory drug (NSAID) use, but it is possible that the association between aspirin use and breast cancer risk might be due to the effect of aspirin on mammographic density.

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.

High-density fine-mapping of a chromosome 10q26 linkage peak suggests association between endometriosis and variants close to CYP2C19.

Objective: To refine a previously reported linkage peak for endometriosis on chromosome 10q26, and conduct follow-up analyses and a fine-mapping association study across the region to identify new candidate genes for endometriosis.

Design: Case-control study.

Setting: Academic research.

Risk of adverse health outcomes associated with frequency and duration of deployment with the Australian Defence Force.

The operational tempo of the Australian Defence Force has increased over the last two decades. We examine the relationship between health of personnel and the frequency and duration of their deployment. Self-reported health measures (number of symptoms, Kessler Psychological Distress Scale, and Post Traumatic Stress Disorder Checklist) were compared for people who had never deployed to those who had deployed only once and for those who had deployed at least twice with at least one deployment to East Timor and one deployment to Afghanistan or Iraq.

Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis.

Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis.

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.

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.

Common genetic variants associated with breast cancer and mammographic density measures that predict disease.

Mammographic density for age and body mass index (BMI) is a heritable risk factor for breast cancer. We aimed to determine if recently identified common variants associated with small gradients in breast cancer risk are associated with mammographic density. We genotyped 497 monozygotic and 330 dizygotic twin pairs and 634 of their sisters from 903 families for 12 independent variants.

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.

Familial correlations in postmenopausal serum concentrations of sex steroid hormones and other mitogens: a twins and sisters study.

Background: Serum concentrations of some hormones are risk factors for certain cancers, but little is known about their familial associations especially for females.

Methods: We measured serum concentrations of estradiol (E(2)), testosterone (T), SHBG, prolactin, and IGF-I for 645 Australian female postmenopausal twins and their sisters [182 monozygotic (MZ) and 107 dizygotic (DZ) pairs and 67 nontwin sisters] using well-established immunoassays. After suitable transformation and adjusting for age, body mass index (BMI), and time since menopause, familial correlations and proportions of variance attributed to genetic (h(2)) and nongenetic factors common to sisterships (c(2)) were estimated under the classic twin multivariate normal model using FISHER.

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.

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.

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.

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).