Relative weight at ages 10 and 16 years and risk of endometriosis: a case-control analysis.

BACKGROUND: Although previous epidemiological studies have shown that women with endometriosis are more likely to be thinner and underweight, it is currently not clear whether this is a true characteristic of women who develop endometriosis or a consequence of their disease and its symptoms. The aim of this study was to investigate the relationship between endometriosis and relative weight in childhood and adolescence, prior to diagnosis. METHODS: This case-control study included 268 Australian women with surgically confirmed moderate to severe endometriosis (cases) and 244 women without endometriosis (controls). Relative weight at ages 10 and 16 years, as recalled and classified ('underweight', 'average weight' and 'overweight') separately by the women themselves and their mothers, was analyzed. RESULTS: Women who reported being overweight at 10 years had an increased risk of endometriosis (OR 2.8; 95% CI 1.1-7.5). Mothers' reports and concordant responses among mother-daughter pairs were consistent with this association. There was no clear evidence of an association between relative weight at 16 years and risk of endometriosis. CONCLUSIONS: These data suggest that being overweight during late childhood is associated with the development of endometriosis; however, the results warrant confirmation in larger study populations.

A comparison of family functioning, temperament, and childhood conditions in monozygotic twin pairs discordant for lifetime bulimia nervosa.

OBJECTIVE: The authors investigated differences between twins in nine pairs of female monozygotic twins in the Australian Twin Registry who were discordant for lifetime bulimia nervosa. METHOD: The twins affected and unaffected by lifetime bulimia nervosa were compared on self-report measures, including a measure of parental bonding, four measures of temperament, and six early-childhood medical conditions. RESULTS: No twins had current bulimia nervosa, and there was no difference in weight or eating status between the affected and unaffected twins. The affected twins reported significantly lower self-esteem and less warmth but more overprotection by their mothers during childhood. CONCLUSIONS: Although limited by the small number of discordant twin pairs and the inability to detect causal relationships, these results suggest that environmental influences that promote low self-esteem may also increase the risk for bulimia nervosa. These temperamental differences may explain the discrepancies in parenting or perceived parenting.

Genetic influences on endometriosis in an Australian twin sample. sueT@qimr.edu.au.

OBJECTIVE: To investigate the prevalence of and twin pair concordance for endometriosis. DESIGN: A questionnaire survey incorporating validation. SETTING: An Australia-wide volunteer sample of female monozygotic (MZ) and dizygotic (DZ) twin pairs from the Australian National Health and Medical Research Council Twin Register. PATIENT(S): Twins were selected only on the basis of previous participation in twin research. INTERVENTION(S): Questionnaires were sent to 3,298 individuals. Information was requested from physicians named by consenting twins. MAIN OUTCOME MEASURE(S): Reported endometriosis, validated where possible by pathology or surgical report. RESULT(S): Three thousand ninety-six (94%) of the twins and 145 (82%) of the physicians responded to the survey. Two hundred fifteen twins reported endometriosis, for a prevalence rate of .07 among question respondents. Tetrachoric twin pair correlations for self-reported endometriosis (MZ: n = 854 and DZ: n = 493) were rMz = .46+/-.09 and rDz = .28 +/-.13. When available medical and pathology reports were included, they changed to rMz =.52 +/-.08 and rDZ = .19+/-.16, suggesting that 51% of the variance of the latent liability to endometriosis may be attributable to additive genetic influences. CONCLUSION(S): These findings support the hypothesis that genes influence liability to endometriosis.

Prevalence of premature ovarian failure in monozygotic and dizygotic twins.

BACKGROUND: Premature ovarian failure (POF) before 40 years of age from natural causes affects approximately 1% of adult women, with minor variations between ethnic groups. A recent case of ovarian transplantation between young monozygotic (MZ) twins in which one had undergone unexplained POF at 14 years has prompted a study of the prevalence of POF. METHODS: Menopausal ages of 832 Australian and UK female twin-pairs were extracted from volunteer national twin registry databases containing medical, reproductive and lifestyle data surveyed by mail questionnaire. Surgical menopause was an exclusion criterion. RESULTS: The prevalence of POF in both MZ and dizygotic (DZ) twins was similar in both registries and 3- to 5-fold greater than the general population at age thresholds 40 and 45 years. No specific factors were found to account for the higher risk of early menopause. Some twins of both zygosities were highly discordant for menopausal age (>or=10 years). Nevertheless, there was significant intra-twin dependence, especially for MZ twins, and the average age difference at last menses was greater in DZ twin-pairs. CONCLUSION: Both MZ and DZ twins are at higher risk of POF. Despite some striking differences within MZ twin-pairs, menopausal ages were more concordant than for DZ twin-pairs, confirming that the timing of menopause has a heritable component.

Age at menarche as a fitness trait: nonadditive genetic variance detected in a large twin sample.

The etiological role of genotype and environment in recalled age at menarche was examined using an unselected sample of 1,177 MZ and 711 DZ twin pairs aged 18 years and older. The correlation for onset of menarche between MZ twins was .65 +/- .03, and that for DZ pairs was .18 +/- .04, although these differed somewhat between four birth cohorts. Environmental factors were more important in the older cohorts (perhaps because of less reliable recall). Total genotypic variance (additive plus nonadditive) ranged from 61% in the oldest cohort to 68% in the youngest cohort. In the oldest birth cohort (born before 1939), there was evidence of greater influence of environmental factors on age at menarche in the second-born twin, although there was no other evidence in the data that birth trauma affected timing. The greater part of the genetic variance was nonadditive (dominance or epistasis), and this is typical of a fitness trait. It appears that genetic nonadditivity is in the decreasing direction, and this is consistent with selection for early menarche during human evolution. Breakdown of inbreeding depression as a possible explanation for the secular decline in age at menarche is discussed.

Genetic and environmental influences on premenstrual symptoms in an Australian twin sample.

BACKGROUND: We aimed to explore the prevalence and factor structure of premenstrual symptoms in a sample of Australian twins; to investigate phenotypic associations between reported premenstrual symptoms, personality and reproductive dimensions; and to identify the relative contributions of genes and environment to premenstrual symptoms and the extent of genetic and environmental covariation with the personality trait Neuroticism and lifetime major depression. METHOD: Seven hundred and twenty female twin pairs (454 monozygotic and 266 dizygotic) from the Australian National Health and Medical Research Council Twin Register reported on experience of 17 premenstrual symptoms during the previous 12 months. In the same questionnaire twins also responded to questions on symptom states, and personality dimensions including neuroticism. Interview data enabling diagnosis of lifetime history of DSM-IV major depression were also available. We fitted univariate and multivariate genetic models to the data. RESULTS: Most frequently reported symptoms were breast tenderness/pain and bloating/weight gain, followed by affective symptoms. Twelve-month prevalence was 24% for the combination of symptoms and functional interference meeting a very rough approximation of DSM-III-R criteria for late luteal dysphoric disorder. Principal factor analysis identified a single premenstrual (PMS) factor. Additive genetic influences (44% of total variance) were identified for PMS. Although we found genetic correlations of 0.62 between reported PMS and neuroticism, and 0 70 with lifetime major depression, 39 % of the genetic variance of PMS was not explained by these factors. CONCLUSIONS: Our findings support the existence of genetic influences on premenstrual symptoms, but we were unable to distinguish between liability to symptom experience and symptom reporting. Retrospective reporting may have contributed to our finding that PMS genes were shared in part with neuroticism and liability to lifetime major depression.

Longitudinal genetic analysis of menstrual flow, pain, and limitation in a sample of Australian twins.

Genetically informative longitudinal data about menstrual disorders allow us to address the extent to which the same genetic risk mechanisms are operating throughout the reproductive life cycle. We investigate the relative contributions of genes and environment to individual differences in menstrual symptomatology reported at two waves, 8 years apart, of a longitudinal Australian twin study. Twins were questioned in 1980-1982 and 1988-1990 about levels of menstrual pain, flow, and perceived limitation by menses. Longitudinal genetic analysis was based on 728 pairs (466 MZ and 262 DZ) who were regularly menstruating at both survey waves. A bivariate Cholesky model was fitted to the two-wave data separately for flow, pain, and limitation variables. The baseline model comprised common genetic and environmental factors influencing responses at both waves and specific effects influencing only the second-wave response. We also included age as a covariate in the model. Proportions of the longitudinally stable variance in menstrual flow, pain, and limitation attributable to genetic and individual environmental effects were calculated for the best-fitting models. Genetic factors accounted for 39% of the longitudinally stable variation in menstrual flow, 55% for pain, and 77% for limitation. The remaining stable variance was due to individual environmental factors (61, 45, and 23%, respectively). Therefore the stable variance over the 8-year interval was largely environmentally influenced for menstrual flow, was approximately equally determined by genetic and by nonshared environmental influences in the case of pain, and was due almost entirely to genetic influences for limitation by periods. We demonstrate for the first time that the same genetic influences are operative throughout the reproductive life span.

Genetics of early cancer detection behaviours in Australian female twins.

Early detection of cervical and breast cancers is an important component of women's health strategy. Screening programmes, health professional interventions and preventive behaviours such as breast self-examination provide the means to this end. Our twin study sought to identify the relative influence of environmental and genetic factors on liability to early cancer detection behaviours, including use of cervical smear tests, mammograms, and breast examination. Additive genetic and random environmental effects models gave the best, most parsimonious fit to the data for each early cancer detection behaviour. The heritability of liability to Pap smear use was 66%, mammogram use 50%, breast examination by a doctor or nurse 38% and breast self-examination 37%. Genetic influences were behaviour-specific; there was no evidence for a common genetic influence on the four behaviours. Potential covariates investigated included age, amount of contact between co-twins, educational level and personality traits such as harm avoidance, novelty seeking, reward dependence, neuroticism, anxiety, depression, self-esteem, perceived control, interpersonal dependency and ways of coping. None were significant. The study was carried out before the implementation of national screening programmes with media campaigns to increase participation rates. Hence follow-up investigation, including data on regularity of behaviours, would be informative.

Potential bias regarding birth weight in historical and contemporary twin data bases.

In this study we examine the hypothesis that monozygotic (MZ) twins in historical databases are less discordant for birth weight due to negative selection of severely discordant MZ twins. Furthermore, we test the hypothesis that MZ twins are less discordant for birth weight when comparing a volunteer based twin registry with a population based twin registry, due to selective registration. Data were available on 3927 twin pairs from the volunteer Australian Twin Registry born before 1964, 3059 volunteer twin pairs from the Netherlands Twin Register born 1987-1989 and 454 Belgian twin pairs from The East Flanders Prospective Twin Survey born 1987-1989. Intrapair relative birth weight differences (RBWD) were computed for MZ and dizygotic (DZ) twins from each twin registry. Comparing birth weight differences between MZ and DZ twins provides support for the hypothesis that MZ twins are subject to a negative selection in historical databases. Furthermore, Australian MZ twins have a lower RBWD compared to Dutch MZ twins when corrected for the RBWD of Australian and Dutch DZ twins, indicating circumstances which only affect MZ twins. Our hypothesis that MZ twins are less discordant for birth weight in a volunteer based twin registry compared to a population based twin registry had to be rejected. We suggest that investigators using historical databases to test the fetal origins hypothesis should be aware of this increased likelihood of selective exclusion of individuals with extreme morphometric parameters at time of birth.

Genetic and non-genetic factors affecting birth-weight and adult Body Mass Index.

Birthweight affects neonatal mortality and morbidity and has been used as a marker of foetal undernutrition in studies of prenatal effects on adult characteristics. It is potentially influenced by genetic and environmental influences on the mother, and effects of foetal genotype, which is partially derived from the maternal genotype. Interpretations of variation in birthweight and associated characteristics as being due to prenatal environment ignore other possible modes of materno-foetal transmission. Subjects were adult twins recruited through the Australian Twin Registry, aged 17 to 87 years, and the sample comprised 1820 men and 4048 women. Twins reported their own birthweight as part of a health questionnaire. Body Mass Index (BMI) was calculated from self-reports of height and weight. Correlations between co-twins' birthweights were high for both monozygotic (r = 0.77) and dizygotic (r = 0.67) pairs, leading to substantial estimates of shared environmental effects (56% of variance) with significant additive genetic (23%) and non-shared environmental (21%) components. Adult BMI was mainly influenced by genetic factors, both additive (36% of variance) and nonadditive (35%). The correlation between birthweight and BMI was positive, in that heavier babies became on average more obese adults. A bivariate model of birthweight and adult BMI showed significant positive genetic (r(g) = 0.16, p = 0.005) and environmental (r(e) = 0.08, p = 0.000011) correlations. Intra-uterine environmental or perinatal influences shared by cotwins exercise a strong influence on birthweight, but the factors which affect both birthweight and adult BMI are partly genetic and partly non-shared environmental.

Pathways to hysterectomy: insights from longitudinal twin research.

OBJECTIVE: We hypothesized that genetic influences act on "liability" to hysterectomy, that secular influences might differentially affect relative importance of genetic and environmental influences, and that the sources of genetic influences could be identified from reported risk factors. STUDY DESIGN: Hysterectomy data from an Australia-wide volunteer sample of female adult monozygotic and dizygotic twins are reported. In 1980 through 1982 a mailed questionnaire was completed by 1232 monozygotic female twin pairs and 751 dizygotic female twin pairs (3966 women) from the Australian Twin Register (wave 1). The same twins were surveyed by questionnaire 8 years later (wave 2). RESULTS: A total of 366 had undergone hysterectomy by wave 1 and a further 198 at wave 2. The twin-pair correlations for liability to hysterectomy at wave 1 (0.61 +/- 0.06 for monozygotic and 0.20 +/- 0.11 for dizygotic) and wave 2 (0.65 +/- 0.05 for monozygotic and 0.32 +/- 0.09 for monozygotic) indicated a substantial genetic contribution. Reported risk factors accounted for only 15% of total variance. CONCLUSION: Genetic influences on liability to hysterectomy were substantial and stable across birth cohorts, but the important sources of genetic influence on liability to hysterectomy are yet to be identified.

Birth weight and age at menopause in Australian female twin pairs: exploration of the fetal origin hypothesis.

In a twin sample where duration of gestation can be controlled, a specific example of the fetal origins hypothesis concerning association between low birth weight and early age at menopause is explored. The hypothesis is based on the physiologically plausible path from intrauterine growth retardation and reduced numbers of primary follicles to an earlier menopause. The sample comprised 323 Australian female twin pairs where both co-twins had reached menopause naturally and reported on their weight at birth. Regression analysis showed no linear association between the two variables (P = 0.371, r(2) = 0.0009). Intra-pair differences in age at menopause were investigated in the context of relative birth weight of co-twins. In 265 pairs an intra-pair birth weight difference was reported. In monozygotic (MZ) pairs (n = 168) this allowed for control of genetic effects as well as gestation duration. No significant differences dependent on birth weight relative to co-twin were found for age at natural menopause in either MZ or dizygotic (DZ) twin pairs, even in pairs whose birth weights differed markedly. There was some indication that twins with premature ovarian failure were heavier at birth than twins with normal or later menopausal age. We conclude that the hypothesis that lower birth weight is associated with earlier menopause is not supported by our data.

Genetic influences on premature parturition in an Australian twin sample.

We investigated possible genetic influences on women's liability to preterm birth, using data from a large sample of Australian female twin pairs. In a 1988-90 questionnaire survey, both members of 905 parous twin pairs (579 monozygotic and 326 dizygotic) reported on whether deliveries had been more than two weeks preterm. Tetrachoric twin pair correlations for first birth were rMZ = 0.20+/-0.11 and rDZ = -0.03+/-0.14, and for any birth were rMZ = 0.30+/-0.08 and rDZ = 0.03+/-0.11. Best-fitting models to data contained only additive genetic influences and individual environmental effects. Heritability was 17% for preterm delivery in first pregnancy, and 27% for preterm delivery in any pregnancy. In the former case, however, we could not reject a model without genetic influences. Although our data did not allow for differentiation of the varying aetiologies of premature parturition, results from this exploratory analysis suggest that further investigation of genetic influences on specific reasons for preterm birth is warranted.

Phenotypic and genetic analyses of a short measure of psychosis-proneness in a large-scale Australian twin study.

Previous genetic analyses of psychosis proneness have been limited by their small sample size. For the purposes of large-scale screening, a 12-item questionnaire was developed through a two-stage process of reduction from the full Chapman and Chapman scales. 3685 individuals (including 1438 complete twin pairs) aged 18-25 years and enrolled in the volunteer Australian Twin Registry returned a mail questionnaire which included this psychosis proneness scale and the Eysenck Personality Questionnaire. Despite the brevity of the questionnaire, item and factor analysis identified four unambiguous and essentially uncorrelated scales. There were (1) Perceptual Aberration--Magical Ideation; (2) Hypomania--Impulsivity/Nonconformity; (3) Social Anhedonia and (4) Physical Anhedonia. Model-fitting analyses showed additive genetic and specific environmental factors were sufficient for three of the four scales, with the Social Anhedonia scale requiring also a parameter for genetic dominance. There was no evidence for the previously hypothesised sex differences in the genetic determination of psychosis-proneness. The potential value of multivariate genetic analysis to examine the relationship between these four scales and dimensions of personality is discussed. The growing body of longitudinal evidence on psychosis-proneness suggests the value of incorporating this brief measure into developmental twin studies.

An Australian twin study of the genetic basis of preeclampsia and eclampsia.

OBJECTIVE: We investigated maternal versus fetal genetic causes of preeclampsia and eclampsia by assessing concordance between monozygotic and dizygotic female co-twins, between female partners of male monozygotic and dizygotic twin pairs, and between female twins and partners of their male co-twins in dizygotic opposite-sex pairs. STUDY DESIGN: Two large birth cohorts of volunteer Australian female twin pairs (N = 1504 pairs and N = 858 pairs) were screened and interviewed, and available medical and hospital records were obtained and reviewed where indicated, with diagnoses assigned according to predetermined criteria. RESULTS: With strict diagnostic criteria used for preeclampsia and eclampsia, no concordant female twin pairs were found. Collapsing diagnoses of definite, probable, or possible preeclampsia or eclampsia resulted in very low genetic recurrence risk estimates. CONCLUSION: Results from these two cohorts of female twin pairs do not support clear, solely maternal genetic influences on preeclampsia and eclampsia. Numbers of parous female partners of male twins were too low for conclusions to be drawn regarding paternal transmission.

Assessing the prevalence of eating disorders in an Australian twin population.

OBJECTIVE: This paper examines the prevalence of disordered eating in a female Australian twin population aged between 28 and 90 years in 1993. METHOD: In two waves of data collection, the eating behaviour of 3869 female twins was first assessed in 1988-1989 by self-report questionnaire and then in 1992-1993 with a telephone interview, using the Semi-Structured Assessment for the Genetics of Alcoholism interview. RESULTS: It was found that about 0.4% of the women have a lifetime prevalence of anorexia nervosa and 1.8% of the group have suffered from bulimia nervosa. The incidence of bulimia nervosa but not anorexia nervosa was markedly higher for those women under 45 (2.3% bulimia nervosa) than for those women 45 years or older. Furthermore, one in three women have at some stage in their life used some extreme method of weight control. CONCLUSIONS: The levels of bulimia nervosa and anorexia nervosa found are commensurate with those found in smaller studies in Australia and other parts of the world. The finding of widespread use of extreme weight control methods is of concern as this behaviour is a well-recognised precursor to more serious eating disorders.

Genetic influences on post-natal depressive symptoms: findings from an Australian twin sample.

BACKGROUND: Conflicting evidence exists on causes of vulnerability to post-natal depression. We investigated genetic and environmental influences on variation in post-natal depressive symptoms (PNDS) following first live birth, and sources of covariation with the personality trait Neuroticism and lifetime major depression occurring post-natally (DEP-PN) and at other times (DEP-XPN) to test for shared genetic influences. METHOD: Retrospective interview and questionnaire data from 838 parous female twin pairs (539 monozygotic, 299 dizygotic) from the Australian National Health and Medical Research Council volunteer adult twin register were used for multivariate genetic model-fitting. Data on PNDS were evaluated for consistency with diagnostic interview assessment. RESULTS: Genetic factors explained 38% of variance in PNDS (95% confidence interval 26-49%) and 25% of the variance in interview-assessed DEP-PN. The genetic correlation between PNDS and lifetime major depression (DEP-PN and DEP-XPN) was low (r(g) = 0.17, 95% confidence interval = 0.09-0.28), suggesting that the questionnaire was measuring a construct other than postnatally occurring major depression, possibly post-natal dysphoria. Associations between PNDS and obstetric factors were very modest. CONCLUSIONS: Findings suggest modest genetic influences on major depression occurring postnatally. Independent and stronger genetic influences identified for post-natal symptomatology or dysphoria (PNDS) justify further investigation.

Genetics of educational attainment in Australian twins: sex differences and secular changes.

The relative effects of genetic and environmental factors in producing individual differences in educational achievement are compared across women and men and over birth cohorts. In a large sample of Australian twin pairs, the heritability of self-reported educational attainment did not vary among women and men born before and after 1950. In a "psychometric" model of twin resemblance, based on separate self-reports in 1981 and 1989, genetic factors explained 57% of the stable variance in educational achievement, while environmental factors shared by twins accounted for 24% of the variance. Corrections for phenotypic assortative mating for educational level, however, suggested that estimated common-environmental effects could be entirely explained by the correlation between additive genetic values for mates. Taking this into account, heritability "true" educational attainment in Australia may be as high as 82% with the remaining variation being due to individual environments or experiences. Unlike previous studies in Scandinavian countries, results in Australia suggest that factors influencing educational success are comparable between women and men and for individuals born at different points during this century.

Structure of disordered eating in a twin community sample.

OBJECTIVE: To describe the types of eating problems experienced by women in an Australian twin population. METHOD: Questions assessing preoccupation with weight or shape, use of various methods of weight control, difficulties with weight control, disordered eating, or binging, were administered to a group of 3,869 female twins. Exploratory and confirmatory factor analyses were used to summarize and describe problematic eating behaviors. RESULTS: For those women experiencing problems with eating, five groups could be identified. These were overweight women who were dissatisfied with their weight and shape, underweight women struggling with anorexic behaviors, women who were having problems with binging, women who were using more extreme methods of weight control such as vomiting, laxatives, and starvation, and overweight women who were using slimming and fluid tablets for weight control. Confirmatory factor analysis suggested that this factor model is an acceptable fit to the data and that the factor structure generalizes well across two groups viz, the first-born and second-born twins. DISCUSSION: It was concluded that future studies aiming to develop a general description of eating problems in the community should specifically assess the purging behaviors used by women.

Genetic analysis of the age at menopause by using estimating equations and Bayesian random effects models.

Multi-wave self-report data on age at menopause in 2182 female twin pairs (1355 monozygotic and 827 dizygotic pairs), were analysed to estimate the genetic, common and unique environmental contribution to variation in age at menopause. Two complementary approaches for analysing correlated time-to-onset twin data are considered: the generalized estimating equations (GEE) method in which one can estimate zygosity-specific dependence simultaneously with regression coefficients that describe the average population response to changing covariates; and a subject-specific Bayesian mixed model in which heterogeneity in regression parameters is explicitly modelled and the different components of variation may be estimated directly. The proportional hazards and Weibull models were utilized, as both produce natural frameworks for estimating relative risks while adjusting for simultaneous effects of other covariates. A simple Markov chain Monte Carlo method for covariate imputation of missing data was used and the actual implementation of the Bayesian model was based on Gibbs sampling using the freeware package BUGS.