Determinants of hepato- and spleno-megaly in Hunan, China: cross-sectional survey data from areas endemic for schistosomiasis

In order to understand the determinants of schistosome-related hepato- and spleno-megaly better, 14 002 subjects aged 3-60 years (59% male; mean age =32 years) were randomly selected from 43 villages, all in Hunan province, China, where schistosomiasis caused by Schistosoma japonicum is endemic. The abdomen of each subject was examined along the mid-sternal (MSL) and mid-clavicular lines, for evidence of current hepato- and/or spleno-megaly, and a questionnaire was used to collect information on the medical history of each individual. Current infections with S. japonicum were detected by stool examination. Almost all (99.8%) of the subjects were ethnically Han by descent and most (77%) were engaged in farming. Although schistosomiasis appeared common (42% of the subjects claiming to have had the disease), only 45% of the subjects said they had received anti-schistosomiasis drugs. Overall, 1982 (14%) of the subjects had S. japonicum infections (as revealed by miracidium-hatching tests and/or Katon Katz smears) when examined and 22% had palpable hepatomegaly (i.e. enlargement of at least 3 cm along the MSL), although only 2.5% had any form of detectable splenomegaly (i.e. a Hackett's grade of at least 1). Multiple logistic regression revealed that male subjects, fishermen, farmers, subjects aged greater than or equal to 25 years, subjects with a history of schistosomiasis, and subjects who had had bloody stools in the previous 2 weeks were all at relatively high risk of hepato- and/or spleno-megaly. In areas moderately endemic for Schistosoma japonicum, occupational exposure and disease history appear to be good predictors of current disease status among older residents. These results reconfirm those reported earlier in the same region.

Fitting genetic models to twin data with binary and ordered categorical responses: A comparison of structural equation modelling and Bayesian hierarchical models

We compare Bayesian methodology utilizing free-ware BUGS (Bayesian Inference Using Gibbs Sampling) with the traditional structural equation modelling approach based on another free-ware package, Mx. Dichotomous and ordinal (three category) twin data were simulated according to different additive genetic and common environment models for phenotypic variation. Practical issues are discussed in using Gibbs sampling as implemented by BUGS to fit subject-specific Bayesian generalized linear models, where the components of variation may be estimated directly. The simulation study (based on 2000 twin pairs) indicated that there is a consistent advantage in using the Bayesian method to detect a correct model under certain specifications of additive genetics and common environmental effects. For binary data, both methods had difficulty in detecting the correct model when the additive genetic effect was low (between 10 and 20%) or of moderate range (between 20 and 40%). Furthermore, neither method could adequately detect a correct model that included a modest common environmental effect (20%) even when the additive genetic effect was large (50%). Power was significantly improved with ordinal data for most scenarios, except for the case of low heritability under a true ACE model. We illustrate and compare both methods using data from 1239 twin pairs over the age of 50 years, who were registered with the Australian National Health and Medical Research Council Twin Registry (ATR) and presented symptoms associated with osteoarthritis occurring in joints of the hand.

The implications of simultaneous smoking initiation for inferences about the genetics of smoking behavior from twin data

We examined early social influences across stages of smoking within the context of a twin study using an environmental exposure specific to smoking: whether twins started smoking at the same time (simultaneous smoking initiation: SSI). We expected that SSI would be a good index of shared social influences on smoking initiation. Rates of SSI were indeed significantly higher in MZ twins and in twins who shared peers and classes, as well as in male twins. With the exception of regular smoking in females, we found no significant difference in estimates of genetic and environmental parameters between SSI and non-SSI pairs for any of the smoking measures that we examined (DSM-IV and Fagerstrom HSI measures of nicotine dependence; DSM-IV nicotine withdrawal; heavy smoking; and in males, regular smoking). For regular smoking in females, allowing for additional shared environmental influences associated with SSI only modestly reduced our estimates of additive genetic variance (56% vs. 68%). These results indicate the important social influences that may occur for smoking initiation do not appear to seriously bias estimates of genetic effects on later stages of smoking.

Biometrical Genetics

Biometrical genetics is the science concerned with the inheritance of quantitative traits. In this review we discuss how the analytical methods of biometrical genetics are based upon simple Mendelian principles. We demonstrate how the phenotypic covariance between related individuals provides information on the relative importance of genetic and environmental factors influencing that trait, and how factors such as assortative mating, gene-environment correlation and genotype-environment interaction complicate such interpretations. Twin and adoption studies are discussed as well as their assumptions and limitations. Structural equation modeling (SEM) is introduced and we illustrate how this approach may be applied to genetic problems. In particular, we show how SEM can be used to address complicated issues such as analyzing the causes of correlation between traits or determining the direction of causation (DOC) between variables. (C) 2002 Elsevier Science B.V. All rights reserved.

Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions., recovery of simulated genetic and environmental correlations becomes possible, Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

Heritability of adult body height: A comparative study of twin cohorts in eight countries

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.

What is a healthy weight for middle aged women?

OBJECTIVE: To explore associations between body mass index (BMI) and selected indicators of health and well-being and to suggest a healthy weight range (based on BMI) for middle aged Australian women. DESIGN: population based longitudinal study (cross-sectional baseline data). SUBJECTS: 13431 women aged 45-49 y who participated in the baseline survey for the Australian Longitudinal Study on Women's Health. RESULTS: Forty-eight percent of women had a BMI>25kg/m(2). Prevalence of medical problems (for example, hypertension, diabetes), surgical procedures (cholescystectomy, hysterectomy) and symptoms (for example, back pain) increased monotonically with BMI, while indicators of health care use (for example, visits to doctors) showed a 'J' shaped relationship with BMI. Scores for several sub-scales of the MOS short form health survey (SF36) (for example, general health, role limitations due to emotional difficulties, social function, mental health and vitality) were optimal when BMI was around 19-24 kg/m(2). After adjustment for area of residence, education, smoking, exercise and menopausal status, low BMI was associated with fewer physical health problems than mid-level or higher BMI, and the nationally recommended BMI range of 20-25 was associated with optimum mental health, lower prevalence of tiredness and lowest use of health services. CONCLUSIONS: Acknowledging the limitations of the cross-sectional nature of these data, the results firmly support the benefits of leanness in terms of reducing the risk of cardiovascular disease, diabetes and gall bladder disease. The findings are moderated, however, by the observation that both low and high BMI are associated with decreased vitality and poorer mental health. The optimal range for BMI appears to be about 19-24 kg/m(2). From a public health perspective this study provides strong support for the recommended BMI range of 20-25 as an appropriate target for the promotion of healthy weight in middle aged Australian women.

Men's perceived health needs

Cross-sectional survey data describing health priorities and needs perceived by men and women living in Newcastle, Australia are compared and contrasted with national health policies. The highest prevalence of felt needs for men were stress (13 percent), cost of medical care (10 percent) and money problems (9 percent); while stress (16 percent), overweight (16 percent) and money problems (15 percent) were highest for women. These contrast with the 2000 National Health Priorities of cancer. mental health, injury, cardiovascular health, diabetes and asthma. We conclude that men's perceived unmet health needs are similar to those of women; while sharing some commonalities, they also differ from health professional priorities. Incorporating felt needs into health service planning and delivery is a critical unmet challenge for government planners.

Analysis of proximal femur DXA scans in growing children: Comparisons of different protocols for cross-sectional 8-month and 7-year longitudinal data

Dual-energy X-ray absorptiometry (DXA) is a widely used method for measuring bone mineral in the growing skeleton. Because scan analysis in children offers a number of challenges, we compared DXA results using six analysis methods at the total proximal femur (PF) and five methods at the femoral neck (FN), In total we assessed 50 scans (25 boys, 25 girls) from two separate studies for cross-sectional differences in bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) and for percentage change over the short term (8 months) and long term (7 years). At the proximal femur for the short-term longitudinal analysis, there was an approximate 3.5% greater change in bone area and BMC when the global region of interest (ROI) was allowed to increase in size between years as compared with when the global ROI was held constant. Trend analysis showed a significant (p < 0.05) difference between scan analysis methods for bone area and BMC across 7 years. At the femoral neck, cross-sectional analysis using a narrower (from default) ROI, without change in location, resulted in a 12.9 and 12.6% smaller bone area and BMC, respectively (both p < 0.001), Changes in FN area and BMC over 8 months were significantly greater (2.3 %, p < 0.05) using a narrower FN rather than the default ROI, Similarly, the 7-year longitudinal data revealed that differences between scan analysis methods were greatest when the narrower FN ROI was maintained across all years (p < 0.001), For aBMD there were no significant differences in group means between analysis methods at either the PF or FN, Our findings show the need to standardize the analysis of proximal femur DXA scans in growing children.

Subtypes of Illicit Drug Users: A Latent Class Analysis of Data From an Australian Twin Sample

This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a 'self-medicating' subgroup is needed.

Twin study of adolescent genetic susceptibility to mosquito bites using ordinal and comparative rating data

Ordinal and comparative rating measures of mosquito attraction and mosquito bite frequency and symptoms were administered in a self-report questionnaire format to a sample of 197 monozygotic and 326 dizygotic Australian adolescent twin pairs at age 12 between 1992 and 1999, in order to investigate the environmental and possibly genetic determinants of variation between individuals. Repeat measures were obtained from the twin pairs at age 14. Ordinal variable measures, although providing some support for genetic effects on mosquito susceptibility, were affected by low repeatability. However, analysis of a comparative rating variable compared with your twin, who is bitten by mosquitoes more often? indicated a strong genetic influence on frequency of being bitten by mosquitoes, with no significant differences observed between males and females. Comparative rating questionnaire items are a potentially valuable tool for complementing and improving the results obtained from more conventional absolute measures. (C) 2000 Wiley-Liss, Inc.

Boston naming test results for healthy older Australians: A longitudinal and cross-sectional study

This study reports on a sample of normal Australian elderly who were assessed for naming ability using the Boston Naming Test (BNT). The study aimed to examine and compare the changes in naming ability, using both longitudinal and cross-sectional analysis, and determine the relationships between naming ability and age, educational level, visual acuity and gender and cultural relevance. Contradictory findings were produced regarding age and were dependent on the research design. Longitudinal analysis showed no age-related change in naming ability in subjects over a four-period. In contrast, cross-sectional analysis showed a weak but significant correlation between age and naming ability. Educational level, visual acuity and gender were unrelated to changes in naming ability over time, and unrelated to naming ability across the cohort of elderly. The Australian elderly performed better on the modified Australian version of the BNT than on the original American version. Thus, clinicians need to be cautious when interpreting the results of the BNT for elderly and for populations outside North America. The results of this study also indicate a need for further longitudinal research of a greater duration to establish age-related decline in naming ability.

Effect of coinfection with STDs and of STD treatment on HIV shedding in genital-tract secretions - Systematic review and data synthesis

Objective: To determine whether coinfection with sexually transmitted diseases (STD) increases HIV shedding in genital-tract secretions, and whether STD treatment reduces this shedding. Design: Systematic review and data synthesis of cross-sectional and cohort studies meeting. predefined quality criteria. Main Outcome Measures: Proportion of patients with and without a STD who had detectable HIV in genital secretions, HIV toad in genital secretions, or change following STD treatment. Results: Of 48 identified studies, three cross-sectional and three cohort studies were included. HIV was detected significantly more frequently in participants infected with Neisseria gonorrhoeae (125 of 309 participants, 41%) than in those without N gonorrhoeae infection (311 of 988 participants, 32%; P = 0.004). HIV was not significantly more frequently detected in persons infected with Chlamydia trachomatis (28 of 67 participants, 42%) than in those without C trachomatis infection (375 of 1149 participants, 33%; P = 0.13). Median HIV load reported in only one study was greater in men with urethritis (12.4 x 10(4) versus 1.51 x 10(4) copies/ml; P = 0.04). In the only cohort study in which this could be fully assessed, treatment of women with any STD reduced the proportion of those with detectable HIV from 39% to 29% (P = 0.05), whereas this proportion remained stable among controls (15-17%), A second cohort study reported fully on HIV load; among men with urethritis, viral load fell from 12.4 to 4.12 x 10(4) copies/ml 2 weeks posttreatment, whereas viral load remained stable in those without urethritis. Conclusion: Few high-quality studies were found. HIV is detected moderately more frequently in genital secretions of men and women with a STD, and HIV load is substantially increased among men with urethritis, Successful STD treatment reduces both of these parameters, but not to control levels. More high-quality studies are needed to explore this important relationship further.

A twin study of psychometric intelligence and efficiency of information processing

Intelligence (IQ) can be seen as the efficiency of mental processes or cognition, as can basic information processing (IP) tasks like those used in our ongoing Memory, Attention and Problem Solving (MAPS) study. Measures of IQ and IP are correlated and both have a genetic component, so we are studying how the genetic variance in IQ is related to the genetic variance in IP. We measured intelligence with five subscales of the Multidimensional Aptitude Battery (MAB). The IP tasks included four variants of choice reaction time (CRT) and a visual inspection time (IT). The influence of genetic factors on the variances in each of the IQ, IP, and IT tasks was investigated in 250 identical and nonidentical twin pairs aged 16 years. For a subset of 50 pairs we have test–retest data that allow us to estimate the stability of the measures. MX was used for a multivariate genetic analysis that addresses whether the variance in IQ and IP measures is possibly mediated by common genetic factors. Analyses that show the modeled genetic and environmental influences on these measures of cognitive efficiency will be presented and their relevance to ideas on intelligence will be discussed.

Estimating HIV incidence rates from age prevalence data in epidemic situations

We present a method of estimating HIV incidence rates in epidemic situations from data on age-specific prevalence and changes in the overall prevalence over time. The method is applied to women attending antenatal clinics in Hlabisa, a rural district of KwaZulu/Natal, South Africa, where transmission of HIV is overwhelmingly through heterosexual contact. A model which gives age-specific prevalence rates in the presence of a progressing epidemic is fitted to prevalence data for 1998 using maximum likelihood methods and used to derive the age-specific incidence. Error estimates are obtained using a Monte Carlo procedure. Although the method is quite general some simplifying assumptions are made concerning the form of the risk function and sensitivity analyses are performed to explore the importance of these assumptions. The analysis shows that in 1998 the annual incidence of infection per susceptible woman increased from 5.4 per cent (3.3-8.5 per cent; here and elsewhere ranges give 95 per cent confidence limits) at age 15 years to 24.5 per cent (20.6-29.1 per cent) at age 22 years and declined to 1.3 per cent (0.5-2.9 per cent) at age 50 years; standardized to a uniform age distribution, the overall incidence per susceptible woman aged 15 to 59 was 11.4 per cent (10.0-13.1 per cent); per women in the population it was 8.4 per cent (7.3-9.5 per cent). Standardized to the age distribution of the female population the average incidence per woman was 9.6 per cent (8.4-11.0 per cent); standardized to the age distribution of women attending antenatal clinics, it was 11.3 per cent (9.8-13.3 per cent). The estimated incidence depends on the values used for the epidemic growth rate and the AIDS related mortality. To ensure that, for this population, errors in these two parameters change the age specific estimates of the annual incidence by less than the standard deviation of the estimates of the age specific incidence, the AIDS related mortality should be known to within +/-50 per cent and the epidemic growth rate to within +/-25 per cent, both of which conditions are met. In the absence of cohort studies to measure the incidence of HIV infection directly, useful estimates of the age-specific incidence can be obtained from cross-sectional, age-specific prevalence data and repeat cross-sectional data on the overall prevalence of HIV infection. Several assumptions were made because of the lack of data but sensitivity analyses show that they are unlikely to affect the overall estimates significantly. These estimates are important in assessing the magnitude of the public health problem, for designing vaccine trials and for evaluating the impact of interventions. Copyright (C) 2001 John Wiley & Sons, Ltd.