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J L Hopper

Publications and source records attributed to J L Hopper.

At least 19 recordsLinked to original sources
PubMed1992

Familial aggregation of a disease consequent upon correlation between relatives in a risk factor measured on a continuous scale.

Correlation between relatives in one or more risk factors for a disease will contribute to the risk in relatives of an affected individual, irrespective of the cause(s) of the correlation. In this paper, a model is proposed to quantify the relation between 1) the correlation (rho) between a random pair of relatives in a quantitative risk factor, 2) the dependence of the probability of being affected on a risk factor, assumed to be a logistic function and summarized by a risk ratio (RR) between upper and lower quartiles, and 3) the resultant disease association between relatives, represented as an odds ratio. For one risk factor, the odds ratio is almost independent of disease frequency across the range 0.001-0.1, and is approximately linearly related to rho on a logarithmic scale. An odds ratio between relatives of about 2 occurs if rho = 1 and RR = 9, if rho = 0.6 and RR = 20, or if rho = 0.3 and RR = 100. For two independent risk factors with the same risk ratio and rho, the resultant odds ratio exceeds unity by about twice as much as when there is one risk factor. That is, even moderate familial aggregation of a disease is consistent with there being one or more strong familial (genetic and/or environmental) risk factors. Illustrations of the model are discussed.

Breast Neoplasms↗
PubMed1992

Early seizures after acute stroke. Risk of late seizures.

The prognosis of early seizures after stroke is controversial. We assessed the incidence of late seizures in 31 patients with early seizures complicating acute stroke and compared this with the incidence of late seizures in 31 matched patients with stroke without early seizures. Ten (32%) of 31 patients with early seizures had late seizures during a mean follow-up period of 26 months. Only three (10%) of 31 patients without early seizures had late seizures during the follow-up period of 28 months, a significantly lower incidence than in patients with early seizures. The risk of seizure recurrence in patients with early seizures did not correlate with stroke type or lesion size as imaged on the computed tomographic scan. We conclude that early seizures are not benign and are associated with a significant risk of seizure recurrence.

Aged↗
PubMed1992

Pedigree analysis of blood pressure in subjects from rural Greece and relatives who migrated to Melbourne, Australia.

Diastolic blood pressure readings taken in 1983-1984 on 1,474 Greek individuals (628 living on the island of Levkada, 846 relatives having migrated to Melbourne, Australia) from 204 two generational pedigrees were analysed. Blood pressure was regressed as a quadratic in age by sex and migrant status, and on temperature. Variance increased with age and was greater in migrant males. The covariance between relatives in different countries was significant. Variation was modeled by a multivariate normal model for pedigree analysis in terms of genetic effects, a common environment effect, and effects particular to an individual. The genetic component was 25.9 mm Hg2, independent of sex and migrant status. Importantly, the common environment component was not significant. The third component was greatest in migrant males. Spouse correlation was -0.09 (SE = 0.03). Exclusion of 86 individuals who reported currently receiving medication for elevated blood pressure stabilised the variance and decreased the genetic component. The data suggest that familial aggregation of diastolic blood pressure is due to genetic factors which produce the same variation in males and females, living on Levkada or in Melbourne. Nongenetic factors explain the greater variation in blood pressure of migrant males living in Melbourne.

Adolescent↗
PubMed1992

The prevalence of glucose intolerance in aborigines and Europids of south-eastern Australia.

Based on oral glucose tolerance testing, the prevalence of diabetes in Australian adults has ranged from 2.3% in Europids in 1966 to 20% in small surveys of Aborigines. We have surveyed Aborigines and Europids simultaneously for further comparison of diabetes prevalence between these population groups. The samples were drawn from two adjacent country towns in south-eastern Australia, where Aborigines and Europids have been in contact for 150 years. By the 2-h (post-75 g oral glucose load) criterion (venous plasma glucose greater than or equal to 11.1 mmol/l), the crude prevalence of diabetes among 306 Aborigines was 7.8%, significantly higher than the 3.4% among 553 Europids (P less than 0.01). The prevalence of impaired glucose tolerance was similar in both groups (6.9% in Aborigines, 6.0% in Europids, no significant difference). Adjustment for the marked differences in age distribution between Aborigines and Europids by direct standardization to the 1980 world population increased the apparent differences, with the finding of a four-fold greater prevalence among Aborigines (8.1% compared with 1.9%). The greater frequency of glucose intolerance among Aborigines appears to persist despite the higher proportion of Europid genetic mix with these urbanized south-eastern groups than with Aborigines from remote settings.

Adult↗
PubMed1992

The epidemiology of genetic epidemiology.

Familial aggregation for disease is important; strong familial risk factors must exist even if the increased risk to a relative of an affected individual is modest. It is in practice difficult, however, to conduct studies in genetic epidemiology which conform to strict epidemiological principles. For twin studies there are two major questions: Are twins 'no different' from the population on which inference is to be made? Are study twins 'no different' to twins in the population? The importance of each question of bias depends on the scientific question, the trait(s) studied, and sampling issues. The strength of the twin design is its ability to refute the null hypothesis that genetic factors do not explain variation in a trait. Following the Popperian paradigm, alternate hypotheses should be considered in depth (both theoretically and empirically), with a design and sample size sufficient to exclude not just naive explanations. More sophisticated statistical techniques are now being applied, so the philosophy, assumptions, and limitations of statistical modelling must be appreciated. The concept of 'heritability' has, in the past, been misunderstood and misused. New advances in DNA technology promise to revolutionise epidemiological thinking, and so case-control-pedigree designs may well become standard tools. The strengths and limitations of studies based on related individuals as the sampling unit are discussed.

Adult↗
PubMed1992

Alcohol use, smoking habits and the Adult Eysenck Personality Questionnaire in adolescent Australian twins [corrected].

In 1988, questionnaires were received from 1,400 twin pairs (17% MZM, 23% MZF, 17% DZM, 19% DZF, 24% DZO) aged 11 to 18, registered with the Australian NHMRC Twin Registry. Twins reported independently on themselves and on the perceived behaviour of their parents, siblings and friends. For smoking and for drinking in the previous month, the prevalence was modelled as a logistic function of age, sex, perceived smoking or drinking behaviour of family and friends, and the Adult Eysenck Personality Questionnaire (AEPQ) scales. Strengths of association were: family behaviour, odds ratio (OR) < or = 2; Extraversion and Psychoticism, interquartile OR approximately 1.6; behaviour of friend, OR approximately 3 to 6. Twin associations were represented by odds ratios. For smoking they were 16 in MZ and 7 in DZ same-sex pairs, and 3 in DZO pairs. Although the former is consistent with genetic factors determining adolescent smoking behaviour, the reduced association in DZO pairs and strong association with smoking by friends argue to the contrary. For drinking, twin odds ratios were 11 in MZM, MZF and DZF pairs, and 4 in DZM and DZO pairs, consistent with genetic factors determining alcohol use in male but not female, adolescents. Twin odds ratios were not influenced by adjustment for the AEPQ scales; this does not support the hypothesis that genetic factors which determine personality also determine smoking or drinking behaviour during adolescence [corrected].

Adolescent↗
PubMed1992

Acute stroke outcome: effects of stroke type and risk factors.

We studied 925 consecutive patients hospitalised with acute stroke to determine how stroke type, age, gender and risk factors influence acute, in-hospital outcome. Stroke types included carotid territory cortical or large subcortical infarction (52%), vertebrobasilar infarction (12%), lacunar infarction (11%), intracerebral haemorrhage (16%), and subarachnoid haemorrhage (9%). Mean age (mean +/- 1 SD) was 66 +/- 15 years, but patients with cerebral infarction were older than those with cerebral haemorrhage. The prevalence of hypertension, diabetes mellitus and cardiac disease increased with age across all stroke types, while the prevalence of smoking decreased with age. Mortality was 19% overall, but varied significantly between stroke types, highest in intracerebral haemorrhage (34%), and lowest in lacunar infarction (1%). Age had a marked adverse effect on mortality, independent of stroke type, the probability of death increasing by 3 +/- 0.5% per year from 20-92 years, whereas gender had no effect. Cardiac disease and diabetes were independent adverse prognostic factors (Odds Ratios 1.6 and 1.5 respectively). Cerebral haemorrhage, age, cardiac disease and diabetes all independently worsen acute stroke outcome.

Acute Disease↗
PubMed1992

The effect of aging on intact PTH and bone density in women.

OBJECTIVE: To determine whether age-related bone loss is negatively associated with serum intact parathyroid hormone (PTH). DESIGN: Survey. SETTING: University hospital outpatient department. PARTICIPANTS: 100 community-dwelling women, age 18 to 80, recruited as a convenience sample. MEASUREMENTS: Dependent variables--bone density at the spine and femoral neck by dual-energy X-ray absorptiometry. Independent variables--age, menopausal status (binary) and intact serum PTH by Allegro immunometric assay. RESULTS: Post-menopausal women had higher serum PTH and lower bone density of spine and femoral neck than premenopausal women. Bone density at the spine decreased with age, but this effect was accounted for by menopausal state. Bone density at the femoral neck decreased with age even after adjusting for menopause. Log PTH was negatively associated with bone density at the femoral neck but not significantly at the spine. Multiple regression analysis adjusting for age and menopause showed no significant association between intact PTH and bone density at the spine or the femoral neck. CONCLUSION: Although this study confirmed the rise in intact PTH with age, there is no evidence that this is the mediator of age-related bone loss.

Absorptiometry, Photon↗
PubMed1991

Longitudinal analysis of lung function growth in healthy children and adolescents.

Lung function and height in 242 8-yr-old and 299 12-yr-old children without known or suspected predisposition to lung disease were measured annually over 6 and 8 yr, respectively. Growth of forced expiratory volume in 1 s (FEV1), vital capacity, and expiratory flow after expiring 50% of vital capacity were statistically modeled by age and height by use of a multivariate normal model for longitudinal data. This method has the flexibility to fit an appropriate (not necessarily linear) mathematical description of average lung function while concurrently modeling the covariance between measures on the same individual. Differences in lung function growth between girls and boys, pre- and post-puberty, showed that girls had a steadier though less pronounced increase in lung function with height. In boys, before puberty there was deficit in lung volume relative to height (not evident in girls), which was compensated for by rapid growth after puberty. The standard error of FEV1 predictions based on current height and age were more than halved when measurements of FEV1, age, and height taken 1 yr before were incorporated. We found evidence for dysanaptic growth in childhood. Fitted models have application to early detection of departures from healthy lung function.

Adolescent↗
PubMed1991

Genetic factors in bone turnover.

Genetic factors are major determinants of adult bone density, however, it is unknown how these effects may be mediated. Since bone mineral density is the net result of bone formation and bone resorption we studied biochemical indices of bone formation (serum osteocalcin) and resorption [fasting urinary calcium:creatinine (Ca/Crt) and hydroxyproline:creatinine (OH/Crt)] in adult female twins; 39 monozygotic (MZ) and 31 dizygotic (DZ) twin pairs (age, mean +/- SEM, MZ: 51.1 +/- 1.5 yrs; DZ: 46.5 +/- 1.5 yrs, P = NS). Of these subjects, 18 MZ twin pairs and 10 DZ twin pairs were postmenopausal. The MZ twin pair correlations (rMZ) for each index of bone turnover exceeded that between DZ pairs (rDZ), but this difference was only significant for osteocalcin (rMZ = 0.81, rDZ = 0.21, P less than 0.001). Similarly, in the postmenopausal group examined alone, the rMZ (r = 0.84) for serum osteocalcin was significantly greater than rDZ (r = -0.003, P less than 0.03). These osteocalcin data imply that 80% of the variance in serum osteocalcin could be explained by genetic factors. Although genetic effects on fasting urinary hydroxyproline:creatine and calcium:creatinine were not demonstrable, these indices may be less precise and specific. The data indicate that circulating osteocalcin, and therefore bone formation, is strongly genetically determined. These studies suggest at least one of the mechanisms of the genetic effect on bone mass relates to the regulation of bone turnover.

Adult↗
PubMed1991

Differences in drinking patterns associated with migration from a Greek island to Melbourne, Australia: a study of sibships.

Siblings (and their families) who have migrated from the Greek island of Levkada to Melbourne, Australia reported markedly lower alcohol consumption (n aged 25-74 = 846, reported consumption 16 g/d for men, 2 g/d for women) when compared with the siblings (and their family members) who stayed on the island (n = 498, 54 g/d for men, 16 g/d for women). Median time since migration exceeded 20 years. Of nonmigrants, 73% drank wine and 88% of these produced all they consumed. They drank wine regularly with the two main meals each day. Some migrants managed a kind of self-sufficiency by home-pressing bulk-purchased grapes, but commoner responses were to purchase beer or wine or to cease drinking alcohol. Migrants who drank wine consumed less than half as much as comparable nonmigrants. The prevalence of drinking on special occasions was not lower in migrants, nor were the amounts drunk. Drinking contexts continued to be those traditional within Greek culture. Among nonmigrant men self-rated health was positively associated with alcohol consumption. In this culture, which has traditionally made heavy use of alcohol and used it primarily as a food, the level and pattern of use changed markedly under changed circumstances--such as the loss of true self-sufficiency and an altered temporal pattern of daily life.

Acculturation↗
PubMed1990

Epileptic seizures in acute stroke.

We evaluated prospectively the incidence of early seizures in 1000 consecutive patients with stroke and transient ischemic attacks to determine whether seizure occurrence correlates with stroke type, pathogenesis, or outcome. Seizures occurred in 44 patients (4.4%; SE, 0.7%), including 10 (15.4%) of 65 (SE, 4.5%) with lobar or extensive hemorrhage, 6 (8.5%) of 71 (SE, 3.3%) with subarachnoid hemorrhage, 24 (6.5%) of 370 (SE, 1.3%) with cortical infarction, and 4 (3.7%) of 109 (SE, 1.8%) with hemispheric transient ischemic attacks. Lacunar infarcts and deep hemorrhages were not associated with seizures. Arteriovenous malformation was a common cause of lobar hemorrhage with early seizures, but in cortical infarcts there was no association between seizure occurrence and pathogenesis. Seizures generally occurred within 48 hours of stroke onset, were usually single, partial, and readily controlled. Seizures were not associated with a higher mortality or worse functional outcome.

Acute Disease↗
PubMed1990

A family study of panic disorder: reanalysis using a regressive logistic model that incorporates a sibship environment.

Previous analysis of affection status in parents and siblings of 117 probands with panic disorder by a log-linear model for binary pedigree data found a common concordance across biological first-degree relatives and no spouse association [Hopper JL, Judd FK, Derrick PL, Burrows GD: Genet Epidemiol 4:33-41, 1987]. In this paper the data were reanalyzed using a regressive logistic model that modelled both vertical transmission and a shared sibship environment. Ascertainment correction was made by a) an "ascertainment assumption-free" procedure, following Ewens and Shute [Theor Pop Biol 30:388-412, 1986] and compared with b) complete ascertainment and c) single ascertainment. Under every scheme there was evidence for vertical transmission from parents to offspring. Inclusion of a sibship environment gave an improved fit, suggesting that vertical transmission alone may not be sufficient to explain the familial aggregation observed in these families. The effects of an affected parent, of the postulated environmental factor (present for all siblings if it was present for one sibling), and of the prevalence of the rare environmental factor were estimated and found to be roughly similar under the different schemes. Model predictions of lifetime prevalence were consistent with other population-based studies. Under the same assumption-free method, standard errors approximately doubled and computation time increased compared with the other ascertainment schemes that made specific, although not necessarily correct, assumptions. The regressive logistic model used less computation time and gave greater insight into the pattern of familial aggregation than did the previous modelling.

Adult↗
PubMed1990

Twin concordance for a binary trait: III. A bivariate analysis of hay fever and asthma.

Self-reported histories of hay fever and asthma were obtained from 3,808 pairs of adult twins 18 years and over registered with the Australian National Health Medical Research Council Twin Registry (1232 MZF, 567 MZM, 751 DZF, 352 DZM, 906 DZO). The prevalence of hay fever and asthma was 0.32 and 0.13, respectively, with little variation with zygosity, sex, and age. The associations between twin pairs for these two traits were analysed, under the assumption of constant prevalences, as a special case of a log-linear model for binary traits in pedigrees using the statistical package GLIM. The model assumption that there are no second- or higher-order interactions was tested in the 2 X 2 X 2 X 2 table of twin by disease outcomes without revealing strong evidence of departure, even in this large data set. The log-linear modelling showed that only three first-order interactions, namely 1) between hay fever in a twin pair, 2) asthma in a twin pair, and 3) hay fever and asthma in the same twin, were necessary to describe the data. The first two interaction terms were significantly larger in identical pairs; the third was independent of zygosity. Under this parsimonious model, there was a significant difference between identical and fraternal pairs in marginal correlation, both in asthma and hay fever, and in the cross-correlation between hay fever in one twin and asthma in the other. This suggests that genetic factors are implicated in both hay fever and asthma and that some of these genetic factors are common (at least among a subgroup of individuals) to both traits.

Adolescent↗
PubMed1990

Incorporation of twins in the regressive logistic model for pedigree disease data.

Segregation and twin disease concordance analyses have assumed a theoretical underlying liability following a multivariate normal distribution. For reasons of computation, of incorporation of measured explanatory variables, and of testing of fit and assumptions, newer analytical methods are being developed. The regressive logistic model (RLM) relies on expressing the pedigree likelihood as a product of conditional probabilities, one for each individual. In addition to logistic regression modelling of measured epidemiological variables on disease prevalence, there is modelling of vertical transmission, of transmission of unmeasured genotypes and of sibship environment. This paper discusses methods for the analysis of binary traits in twins and in pedigrees. Some extensions to the RLM for pedigrees which include twins are proposed. These enable exploration of twin concordance in the context of the twins' common parenthood, the sibship similarities within the family, and the twins' similarity in age, sex, genes and environment.

Asthma↗
PubMed1990

Genetics of asthma and hay fever in Australian twins.

The occurrence of self-reported asthma/wheezing and hay fever among 3,808 pairs of twins from the Australian National Health and Medical Research Council Twin Registry was examined for evidence of genetic transmission by path analytic methods. The cumulative prevalence of asthma or wheezing was 13.2% and of hay fever, 32%. There were significant correlations in liability to reported disease among twins, and these were higher in monozygotic twins (MZ) (r = 0.65) than in dizygotic twins (DZ) (r = 0.25), and in male MZ twins (r = 0.75) compared with female MZ twins (r = 0.60). Analysis under the assumptions of the classic twin model suggested that there were genetic factors common to asthma and hay fever, with a correlation in genetic liability to the traits of 0.52 for men and 0.65 for women. These genes acted substantially in a nonadditive fashion in men but not in women. As the genetic correlation was significantly less than unity, this implied additional genetic factors influencing either or both diseases individually. The estimated heritability of these diseases was 60 to 70% in this population. Environmental causes of both diseases also were correlated (r = 0.53 for men and 0.33 for women). Cigarette smoking was only weakly associated with wheezing.

Adult↗