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1.
Aust N Z J Public Health ; 40(1): 10-5, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26714194

ABSTRACT

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.


Subject(s)
Life Change Events , Mental Health , Military Personnel/psychology , Stress Disorders, Post-Traumatic/psychology , Veterans/psychology , Adult , Australia , Cross-Sectional Studies , Female , Health Status , Humans , Male , Middle Aged , Multivariate Analysis , Regression Analysis , Retrospective Studies , Self Report , Young Adult
2.
Cancer Epidemiol Biomarkers Prev ; 22(12): 2395-403, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24130221

ABSTRACT

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. We estimated associations using multilevel mixed-effects linear regression and studied familial aspects using a multivariate normal model. RESULTS: The proportions of variance explained by age, body mass index (BMI), and other risk factors, respectively, were 4%, 1%, and 4% for dense area; 7%, 14%, and 4% for percent dense area; and 7%, 40%, and 1% for nondense area. Associations with dense area and percent dense area were in opposite directions than for nondense area. After adjusting for measured factors, the correlations of dense area with percent dense area and nondense area were 0.84 and -0.46, respectively. The MZ, DZ, and sister pair correlations were 0.59, 0.28, and 0.29 for dense area; 0.57, 0.30, and 0.28 for percent dense area; and 0.56, 0.27, and 0.28 for nondense area (SE = 0.02, 0.04, and 0.03, respectively). CONCLUSIONS: Under the classic twin model, 50% to 60% (SE = 5%) of the variance of mammographic density measures that predict breast cancer risk are due to undiscovered genetic factors, and the remainder to as yet unknown individual-specific, nongenetic factors. IMPACT: Much remains to be learnt about the genetic and environmental determinants of mammographic density.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/epidemiology , Mammography/methods , Siblings , Twins, Dizygotic , Twins, Monozygotic , Age Factors , Australia/epidemiology , Body Mass Index , Breast/pathology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Case-Control Studies , Cohort Studies , Female , Genetic Predisposition to Disease , Humans , Mammography/instrumentation , Middle Aged , Predictive Value of Tests
3.
Nat Genet ; 44(12): 1355-9, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23104006

ABSTRACT

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 = 3.6 × 10(-3)), and we confirm association of rs7521902 at 1p36.12 near WNT4. In addition, we establish an association of rs13394619 in GREB1 at 2p25.1 with endometriosis and identify a newly associated locus at 12q22 near VEZT (rs10859871). Excluding cases of European ancestry of minimal or unknown severity, we identified additional previously unknown loci at 2p14 (rs4141819), 6p22.3 (rs7739264) and 9p21.3 (rs1537377). All seven SNP effects were replicated in an independent cohort and associated at P <5 × 10(-8) in a combined analysis. Finally, we found a significant overlap in polygenic risk for endometriosis between the genome-wide association cohorts of European and Japanese descent (P = 8.8 × 10(-11)), indicating that many weakly associated SNPs represent true endometriosis risk loci and that risk prediction and future targeted disease therapy may be transferred across these populations.


Subject(s)
Endometriosis/genetics , Genetic Loci , Genetic Predisposition to Disease , Genome-Wide Association Study , Asian People/genetics , Carrier Proteins/genetics , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 2/genetics , Chromosomes, Human, Pair 6/genetics , Chromosomes, Human, Pair 7/genetics , Chromosomes, Human, Pair 9/genetics , Cohort Studies , Female , Humans , Membrane Proteins/genetics , Neoplasm Proteins/genetics , Polymorphism, Single Nucleotide , Risk , Severity of Illness Index , White People/genetics , Wnt4 Protein/genetics
4.
Am J Hum Genet ; 91(4): 621-8, 2012 Oct 05.
Article in English | MEDLINE | ID: mdl-23040493

ABSTRACT

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.


Subject(s)
Fatty Acid Synthase, Type I/genetics , Genetic Linkage , Genome-Wide Association Study/methods , Leiomyoma/genetics , Uterine Neoplasms/genetics , Alleles , Cohort Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Hysterectomy/methods , Leiomyoma/surgery , Linkage Disequilibrium , Lod Score , Monocarboxylic Acid Transporters/genetics , Polymorphism, Single Nucleotide , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Siblings , Symporters , Uterine Neoplasms/surgery
5.
Hum Reprod ; 27(12): 3616-21, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23010532

ABSTRACT

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.


Subject(s)
Endometriosis/genetics , Genes, ras/genetics , MicroRNAs/genetics , 3' Untranslated Regions , Case-Control Studies , Female , Genome-Wide Association Study , Humans , MicroRNAs/metabolism , Polymorphism, Single Nucleotide , White People/genetics , ras Proteins/genetics
6.
BMC Psychiatry ; 12: 88, 2012 Jul 26.
Article in English | MEDLINE | ID: mdl-22830494

ABSTRACT

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.


Subject(s)
Life Change Events , Mental Health , Military Personnel/psychology , Stress Disorders, Post-Traumatic/diagnosis , Stress, Psychological/diagnosis , Veterans/psychology , Adult , Australia , Cross-Sectional Studies , Female , Health Status , Humans , Male , Middle Aged , Self Report , Stress Disorders, Post-Traumatic/psychology , Stress, Psychological/psychology , Warfare
7.
Int J Audiol ; 51(4): 294-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22149463

ABSTRACT

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.


Subject(s)
Audiometry , Hearing Loss/diagnosis , Mass Screening/methods , Military Personnel , Self Report , Acoustic Stimulation , Adult , Auditory Threshold , Australia/epidemiology , Female , Hearing Loss/epidemiology , Hearing Loss/physiopathology , Hearing Loss/psychology , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , Sensitivity and Specificity
8.
Mil Med ; 176(4): 461-7, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21539171

ABSTRACT

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.


Subject(s)
Military Personnel/statistics & numerical data , Noise, Occupational/adverse effects , Occupational Exposure/adverse effects , Tinnitus/epidemiology , Adult , Australia/epidemiology , Chemical Hazard Release , Female , Humans , Male , Metals, Heavy/adverse effects , Pesticides/adverse effects , Prevalence , Self Report , Smoke/adverse effects , Smoking/adverse effects , Solvents/adverse effects , Tinnitus/etiology , Vehicle Emissions , Young Adult
9.
Fertil Steril ; 95(7): 2236-40, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21497341

ABSTRACT

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. PATIENT(S): Cases=3,223 women with surgically confirmed endometriosis; controls=1,190 women without endometriosis and 7,060 population samples. INTERVENTION(S): Analysis of 11,984 single nucleotide polymorphisms on chromosome 10. MAIN OUTCOME MEASURE(S): Allele frequency differences between cases and controls. RESULT(S): Linkage analyses on families grouped by endometriosis symptoms (primarily subfertility) provided increased evidence for linkage (logarithm of odds score=3.62) near a previously reported linkage peak. Three independent association signals were found at 96.59 Mb (rs11592737), 105.63 Mb (rs1253130), and 124.25 Mb (rs2250804). Analyses including only samples from linkage families supported the association at all three regions. However, only rs11592737 in the cytochrome P450 subfamily C (CYP2C19) gene was replicated in an independent sample of 2,079 cases and 7,060 population controls. CONCLUSION(S): The role of the CYP2C19 gene in conferring risk for endometriosis warrants further investigation.


Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Chromosome Mapping , Chromosomes, Human, Pair 10 , Endometriosis/genetics , Genetic Linkage , Polymorphism, Single Nucleotide , Case-Control Studies , Cytochrome P-450 CYP2C19 , Endometriosis/enzymology , England , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Odds Ratio , Phenotype , Queensland , Risk Assessment , Risk Factors
10.
Mol Hum Reprod ; 17(2): 92-103, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20935158

ABSTRACT

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.


Subject(s)
Endometriosis/genetics , Endometrium/metabolism , Genetic Association Studies , MicroRNAs/genetics , Polymorphism, Single Nucleotide , Adult , Cyclin-Dependent Kinase Inhibitor Proteins/genetics , Female , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Middle Aged , Polymerase Chain Reaction , Risk , Sequence Alignment , Tumor Necrosis Factor-alpha/genetics , Wolf-Hirschhorn Syndrome/genetics
11.
Nat Genet ; 43(1): 51-4, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21151130

ABSTRACT

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. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10⁻7, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10⁻9, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10⁻³, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10⁻9 (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10.


Subject(s)
Chromosomes, Human, Pair 15/genetics , Endometriosis/genetics , Genome, Human/genetics , Genome-Wide Association Study , Australia , Basic-Leucine Zipper Transcription Factors/genetics , Cohort Studies , Female , Genetic Loci , Genetic Predisposition to Disease , Homeobox A10 Proteins , Homeodomain Proteins/genetics , Humans , Odds Ratio , Risk Factors , United Kingdom , United States
12.
Mil Med ; 175(4): 267-72, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20446502

ABSTRACT

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.


Subject(s)
Health Status , Military Personnel/statistics & numerical data , Smoking/epidemiology , Adult , Australia/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Melanesia/epidemiology , Prevalence , Risk Factors , Stress, Psychological/epidemiology , Young Adult
13.
Cancer Res ; 70(4): 1449-58, 2010 Feb 15.
Article in English | MEDLINE | ID: mdl-20145138

ABSTRACT

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. Mammographic dense area, percent dense area, and nondense area were measured by three observers using a computer-thresholding technique. Associations with mammographic density measures adjusted for age, BMI, and other determinants were estimated (a) cross-sectionally using a multivariate normal model for pedigree analysis (P(x)), (b) between sibships, and (c) within sibships using orthogonal transformations of outcomes and exposures. A combined test of association (P(c)) was derived using the independent estimates from b and c. We tested if the distributions of P values across variants differed from the uniform distribution (P(u)). For dense area and percent dense area, the distributions of P(c) values were not uniform (both P(u) <0.007). Consistent with their breast cancer associations, rs3817198 (LSP1) and rs13281615 (8q) were associated with dense area and percent dense area (all P(x) and P(c) <0.05), and rs889312 (MAP3K1), rs2107425 (H19), and rs17468277 (CASP8) were marginally associated with dense area (some P(x) or P(c) <0.05). All associations were independent of menopausal status. At least two common breast cancer susceptibility variants are associated with mammographic density measures that predict breast cancer. These findings could help elucidate how those variants and mammographic density measures are associated with breast cancer susceptibility.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Disease Susceptibility/diagnosis , Mammary Glands, Human/cytology , Polymorphism, Single Nucleotide , Adult , Age Factors , Aged , Breast Neoplasms/pathology , Cell Count , Cross-Sectional Studies , Disease Susceptibility/pathology , Female , Gene Frequency , Humans , Mammary Glands, Human/anatomy & histology , Mammary Glands, Human/pathology , Mammography , Middle Aged , Prognosis , Risk Factors , Siblings , Twins
14.
Am J Obstet Gynecol ; 202(6): 534.e1-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20022587

ABSTRACT

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.


Subject(s)
Dysmenorrhea/complications , Endometriosis/complications , Endometriosis/diagnosis , Adolescent , Adult , Age Factors , Age of Onset , Australia , Case-Control Studies , Child , Dysmenorrhea/diagnosis , Female , Health Surveys , Humans , Menarche/physiology , Menstrual Cycle/physiology , Middle Aged , Odds Ratio , Surveys and Questionnaires
15.
J Clin Endocrinol Metab ; 94(12): 4793-800, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19850695

ABSTRACT

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. RESULTS: For all serum concentrations except prolactin, MZ, DZ, and sister pairs were correlated (P < 0.001). MZ correlations were in the range 0.5-0.7, and for all serum concentrations, there were no differences between DZ and sister correlations. MZ correlations were greater than DZ and sister correlations for log SHBG (P = 0.0001), IGF-I (P = 0.0002), and square-root T (P = 0.007) but not log E(2) (P = 0.3), and the respective h(2) estimates were 0.56 (SE = 0.14), 0.53 (0.17), 0.39 (0.14), and 0.14 (0.16). For log E(2) and square-root T, c(2) estimates were 0.39 (0.14) and 0.22 (0.12). CONCLUSION: There are strong familial correlations in postmenopausal SHBG, IGF-I, and to a lesser extent T, which are consistent with a genetic etiology. For E(2), and to a lesser extent T, correlations are consistent with substantial nongenetic familial factors. The latter might include maternal effects.


Subject(s)
Gonadal Steroid Hormones/blood , Gonadal Steroid Hormones/genetics , Mitogens/blood , Postmenopause/blood , Postmenopause/genetics , Adult , Aged , Australia , Estradiol/blood , Female , Humans , Insulin-Like Growth Factor I/metabolism , Middle Aged , Prolactin/blood , Sex Hormone-Binding Globulin/metabolism , Testosterone/blood
16.
Genet Med ; 11(3): 193-201, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19287242

ABSTRACT

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.


Subject(s)
Genetic Predisposition to Disease/genetics , Genetic Testing/statistics & numerical data , Insurance Selection Bias , Insurance, Life , Prejudice , Adult , Australia , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Consumer Health Information , Female , Genetic Predisposition to Disease/psychology , Genetic Privacy/economics , Genetic Privacy/psychology , Genetic Testing/psychology , Hemochromatosis/diagnosis , Hemochromatosis/genetics , Humans , Huntington Disease/diagnosis , Huntington Disease/genetics , Male , Middle Aged , Perception , Polycystic Kidney Diseases/diagnosis , Polycystic Kidney Diseases/genetics
17.
Int J Eat Disord ; 42(6): 492-7, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19235851

ABSTRACT

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.


Subject(s)
Anorexia Nervosa/genetics , Anorexia Nervosa/psychology , Bulimia Nervosa/genetics , Bulimia Nervosa/psychology , Diseases in Twins/genetics , Diseases in Twins/psychology , Hyperphagia/genetics , Hyperphagia/psychology , Social Environment , Weight Loss , Adult , Aged , Aged, 80 and over , Female , Humans , Interviews as Topic , Middle Aged , Personality Assessment/statistics & numerical data , Phenotype , Psychometrics , Risk Factors , Twins, Dizygotic/genetics , Twins, Dizygotic/psychology , Twins, Monozygotic/genetics , Twins, Monozygotic/psychology
18.
Neuropsychologia ; 47(2): 330-7, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18824185

ABSTRACT

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.


Subject(s)
Functional Laterality/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Algorithms , Australia/epidemiology , Birth Weight/physiology , Child , Cohort Studies , Female , Humans , Male , Middle Aged , Models, Statistical , Netherlands/epidemiology , Reproducibility of Results , Twins , Twins, Dizygotic , Twins, Monozygotic
19.
Genet Epidemiol ; 33(2): 105-13, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18636479

ABSTRACT

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.


Subject(s)
Endometriosis/epidemiology , Endometriosis/genetics , Migraine Disorders/epidemiology , Migraine Disorders/genetics , Adult , Aged , Australia/epidemiology , Comorbidity , Endometriosis/complications , Female , Genetic Predisposition to Disease , Humans , Middle Aged , Migraine Disorders/complications , Registries , Risk Factors , Twins, Dizygotic , Twins, Monozygotic
20.
Aust N Z J Public Health ; 32(6): 529-34, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19076743

ABSTRACT

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.


Subject(s)
Adaptation, Psychological , Military Medicine/statistics & numerical data , Military Personnel/statistics & numerical data , Population Surveillance , Australia , Humans , Male , Military Personnel/psychology , Pilot Projects , Public Health
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