Biomedical subjects

N G Martin

Publications and source records attributed to N G Martin.

At least 55 records · Page 3Linked to original sources

PubMed2001

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.

Adult↗

PubMed2001

Towards a molecular epidemiology of alcohol dependence: analysing the interplay of genetic and environmental risk factors.

BACKGROUND: Progress in identifying genetic factors protective against alcohol dependence (AlcD) requires a paradigm shift in psychiatric epidemiology. AIMS: To integrate analysis of research into the genetics of alcoholism. METHOD: Data from prospective questionnaire and interview surveys of the Australian twin panel, and from a subsample who underwent alcohol challenge, were analysed. RESULTS: In men, effects of alcohol dehydrogenase ADH2*1/*2 genotype or high alcohol sensitivity (risk-decreasing), and of history of childhood conduct disorder, or having monozygotic co-twin or twin sister with AlcD (risk-increasing) were significant and comparable in magnitude. Religious affiliation (Anglican versus other) was associated with the ADH2 genotype, but did not explain the associations with AlcD symptoms. No protective effect of the ADH2*1/*2 genotype was observed in women. CONCLUSIONS: The early onset and strong familial aggregation of AlcD, and opportunity for within-family tests of genetic association to avoid confounding effects, make epidemiological family studies of adolescents and young adults and their families a priority.

Adult↗

PubMed2001

Height discordance in monozygotic females is not attributable to discordant inactivation of X-linked stature determining genes.

We tested the hypothesis that X-linked genes determining stature which are subject to skewed or non-random X-inactivation can account for discordance in height in monozygotic female twins. Height discordant female monozygotic adult twins (20 pairs) were identified from the Australian Twin Registry, employing the selection criteria of proven monozygosity and a measured height discordance of at least 5 cm. Differential X-inactivation was examined in genomic DNA extracted from peripheral lymphocytes by estimating differential methylation of alleles at the polymorphic CAG triplet repeat of the Androgen receptor gene (XAR). There were 17/20 MZ pairs heterozygous at this locus and informative for analysis. Of these, 10/17 both had random X-inactivation, 5/17 showed identical X-inactivation patterns of non random inactivation and 2/17 (12%) showed discordant X-inactivation. There was no relationship between inactivation patterns and self-report chorionicity. We conclude that non-random X-inactivation does not appear to be a major contributor to intra-pair height discordance in female MZ twins.

Adult↗

PubMed2001

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.

Adolescent↗

PubMed2001

Increasing the response rate to a mailed questionnaire by including more stamps on the return envelope: a cotwin control study.

Twins taking part in two unrelated studies were sent a questionnaire together with a self-addressed envelope that either carried one or multiple (up to 5) stamps to the same value. The unprompted proportion of questionnaires returned (before commencement of telephone reminder calls) was increased from 62% to 71% in one study, and from 43% to 52% in the other study (test for common odds ratio in studies, p = 0.04).

Humans↗

PubMed2001

Predictors of non-response to a questionnaire survey of a volunteer twin panel: findings from the Australian 1989 twin cohort.

Questionnaire surveys, while more economical, typically achieve poorer response rates than interview surveys. We used data from a national volunteer cohort of young adult twins, who were scheduled for assessment by questionnaire in 1989 and by interview in 1996-2000, to identify predictors of questionnaire non-response. Out of a total of 8536 twins, 5058 completed the questionnaire survey (59% response rate), and 6255 completed a telephone interview survey conducted a decade later (73% response rate). Multinomial logit models were fitted to the interview data to identify socioeconomic, psychiatric and health behavior correlates of non-response in the earlier questionnaire survey. Male gender, education below University level, and being a dizygotic rather than monozygotic twin, all predicted reduced likelihood of participating in the questionnaire survey. Associations between questionnaire response status and psychiatric history and health behavior variables were modest, with history of alcohol dependence and childhood conduct disorder predicting decreased probability of returning a questionnaire, and history of smoking and heavy drinking more weakly associated with non-response. Body-mass index showed no association with questionnaire non-response. Despite a poor response rate to the self-report questionnaire survey, we found only limited sampling biases for most variables. While not appropriate for studies where socioeconomic variables are critical, it appears that survey by questionnaire, with questionnaire administration by telephone to non-responders, will represent a viable strategy for gene-mapping studies requiring that large numbers of relatives be screened.

Adult↗

PubMed2001

A twin study of the etiology of prolonged fatigue and immune activation.

Risk factors to prolonged fatigue syndromes (PFS) are controversial. Pre-morbid and/or current psychiatric disturbance, and/or disturbed cell-mediated immunity (CMI), have been proposed as etiologic factors. Self-report measures of fatigue and psychologic distress and three in vitro measures of CMI were collected from 124 twin pairs. Crosstwin-crosstrait correlations were estimated for the complete monozygotic (MZ; 79 pairs) and dizygotic (DZ; 45 pairs) twin groups. Multivariate genetic and environmental models were fitted to explore the patterns of covariation between etiologic factors. For fatigue, the MZ correlation was more than double the DZ correlation (0.49 versus 0.16) indicating strong genetic control of familial aggregation. By contrast, for in vitro immune activation measures MZ and DZ correlations were similar (0.49-0.69 versus 0.42-0.53) indicating the etiologic role of shared environments. As small univariate associations were noted between prolonged fatigue and the in vitro immune measures (r = -0.07 to -0.12), multivariate models were fitted. Relevant etiologic factors included: a common genetic factor accounting for 48% of the variance in fatigue which also accounted for 4%, 6% and 8% reductions in immune activation; specific genetic factors for each of the in vitro immune measures; a shared environment factor influencing the three immune activation measures; and, most interestingly, unique environmental influences which increased fatigue but also increased markers of immune activation. PFS that are associated with in vitro measures of immune activation are most likely to be the consequence of current environmental rather than genetic factors. Such environmental factors could include physical agents such as infection and/or psychologic stress.

Age Factors↗

PubMed2001

An integrative approach for studying the etiology of alcoholism and other addictions.

Studies of alcoholism etiology often focus on genetic or psychosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions--behavioral undercontrol, pharmacologic vulnerability, negative affect regulation--addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

Alcoholism↗

PubMed2001

The influence of genetic and environmental factors in estimations of current body size, desired body size, and body dissatisfaction.

The objective was to investigate the genetic epidemiology of figural stimuli. Standard figural stimuli were available from 5,325 complete twin pairs: 1,751 (32.9%) were monozygotic females, 1,068 (20.1%) were dizygotic females, 752 (14.1%) were monozygotic males, 495 (9.3%) were dizygotic males, and 1,259 (23.6%) were dizygotic male-female pairs. Univariate twin analyses were used to examine the influences on the individual variation in current body size and ideal body size. These data were analysed separately for men and women in each of five age groups. A factorial analysis of variance, with polychoric correlations between twin pairs as the dependent variable, and age, sex, zygosity, and the three interaction terms (age x sex, age x zygosity, sex x zygosity) as independent variables, was used to examine trends across the whole data set. Results showed genetic influences had the largest impact on the individual variation in current body size measures, whereas non-shared environmental influences were associated with the majority of individual variation in ideal body size. There was a significant main effect of zygosity (heritability) in predicting polychoric correlations for current body size and body dissatisfaction. There was a significant main effect of gender and zygosity in predicting ideal body size, with a gender x zygosity interaction. In common with BMI, heritability is important in influencing the estimation of current body size. Selection of desired body size for both men and women is more strongly influenced by environmental factors.

Adolescent↗

PubMed2001

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.

Adolescent↗

PubMed2001

Effects of alcohol consumption on indices of iron stores and of iron stores on alcohol intake markers.

BACKGROUND: Alcohol increases body iron stores. Alcohol and iron may increase oxidative stress and the risk of alcohol-related liver disease. The relationship between low or "safe" levels of alcohol use and indices of body iron stores, and the factors that affect the alcohol-iron relationship, have not been fully characterized. Other aspects of the biological response to alcohol use have been reported to depend on iron status. METHODS: We have measured serum iron, transferrin, and ferritin as indices of iron stores in 3375 adult twin subjects recruited through the Australian Twin Registry. Information on alcohol use and dependence and smoking was obtained from questionnaires and interviews. RESULTS: Serum iron and ferritin increased progressively across classes of alcohol intake. The effects of beer consumption were greater than those of wine or spirits. Ferritin concentration was significantly higher in subjects who had ever been alcohol dependent. There was no evidence of interactions between HFE genotype or body mass index and alcohol. Alcohol intake-adjusted carbohydrate-deficient transferrin was increased in women in the lowest quartile of ferritin results, whereas adjusted gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase values were increased in subjects with high ferritin. CONCLUSIONS: Alcohol intake at low level increases ferritin and, by inference, body iron stores. This may be either beneficial or harmful, depending on circumstances. The response of biological markers of alcohol intake can be affected by body iron stores; this has implications for test sensitivity and specificity and for variation in biological responses to alcohol use.

Adult↗

PubMed2001

Variation in alcohol pharmacokinetics as a risk factor for alcohol dependence.

BACKGROUND: The significant association between alcohol dehydrogenase (ADH)-2 genotype and alcohol-dependence risk, demonstrated in both Asian and non-Asian populations, suggests a link between the metabolism of alcohol (ethanol) and individual differences in susceptibility to dependence. METHODS: We tested this hypothesis by following up on subjects who took part in the Alcohol Challenge Twin Study conducted in 1979-1981 and comparing the blood and breath alcohol results in that study between subjects who subsequently did or did not meet diagnostic criteria for lifetime alcohol dependence in 1992-1993. RESULTS: Subjects who met DSM-III-R criteria for lifetime alcohol dependence at follow-up had higher blood and breath alcohol values after alcohol challenge than never-dependent subjects. Multivariate analysis showed independent effects of susceptibility to alcohol dependence and smoking status on blood alcohol concentrations, whereas habitual alcohol intake at the time of the initial study had marginally significant effects. The risk of alcohol dependence was 2-fold higher in men and 3-fold higher in women with blood or breath alcohol concentrations in the highest quartile than in the lowest quartile. CONCLUSIONS: In view of this association and the known genetic influences on both alcohol pharmacokinetics and alcohol dependence, it is probable that part of the heritability of dependence is mediated by genes (other than the known ADH2 and ADH3 polymorphisms) affecting alcohol metabolism.

Adolescent↗

PubMed2000

Androgen receptor exon 1 CAG repeat length and risk of ovarian cancer.

Epidemiological studies indicate that ovarian cancer is an endocrine-related tumour. We conducted a case-control comparison to assess the androgen receptor (AR) exon 1 polymorphic CAG repeat length (CAG(n)) as a risk factor for epithelial ovarian cancer. AR CAG(n) was determined for 319 case subjects with ovarian adenocarcinoma and 853 unaffected control subjects (comprising 300 unrelated adult female monozygotic twins, and 553 adult females sampled randomly from the population using the electoral rolls). The CAG(n) distributions of case subjects and control subjects were compared as a continuum, and by dichotomising alleles according to different CAG(n) cut-points. Logistic regression was used to calculate age-adjusted odds ratio (OR) estimates. Analyzed as a continuous variable, there was no difference between case subjects and control subjects for the smaller, larger or average allele sizes of the CAG(n) genotype, before or after adjusting for age. The mean (95% CI) for the average CAG(n) was 22.0 (21.8-22.2) for case subjects and 22.0 (21.9-22.1) for control subjects (p>.9). Analysis of CAG(n) as a dichotomous variable showed no difference between case subjects and control subjects for the median cutpoint (>/= 22), or for another cut-point previously reported to act as a modifier of breast cancer risk (>/= 29). Our data provide no evidence for an association between ovarian cancer risk and the genotype defined by the AR exon 1 CAG(n) polymorphism, although we cannot exclude small effects, or threshold effects in a small subgroup.

Adenocarcinoma↗

PubMed2000

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.

Adult↗

PubMed2000

Effects of HFE C282Y and H63D polymorphisms and polygenic background on iron stores in a large community sample of twins.

The aim of this study was to assess and to compare the role of HFE polymorphisms and other genetic factors in variation in iron stores. Blood samples were obtained from 3,375 adult male and female twins (age range 29-82 years) recruited from the Australian Twin Registry. There were 1,233 complete pairs (562 monozygotic and 571 dizygotic twins). Serum iron, transferrin, transferrin saturation with iron, and ferritin were measured, and the HFE C282Y and H63D genotypes were determined. The frequency of the C282Y allele was.072, and that of the H63D allele was.141. Significant sources of variation in the indices of iron status included age, sex, age-sex interaction, body-mass index, and both the C282Y and H63D genotypes. The iron, transferrin, and saturation values of CC and CY subjects differed significantly, but the ferritin values did not. After correction for age and body-mass index, 23% and 31% of the variance in iron, 66% and 49% of the variance in transferrin, 33% and 47% of the variance in transferrin saturation, and 47% and 47% of the variance in ferritin could be explained by additive genetic factors, for men and women, respectively. HFE C282Y and H63D variation accounted for <5% of the corrected phenotypic variance, except for saturation (12% in women and 5% in men). We conclude that HFE CY and HD heterozygotes differ in iron status from the CC and HH homozygotes and that serum transferrin saturation is more affected than is serum ferritin. There are highly significant effects of other as-yet-unidentified genes on iron stores, in addition to HFE genotype.

Adult↗

PubMed2000

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.

Adolescent↗

PubMed2000

Early sexual abuse and lifetime psychopathology: a co-twin-control study.

BACKGROUND: This study was designed to determine lifetime prevalence of psychiatric disorders among twins who reported childhood sexual abuse (CSA), and to compare these rates with those among non-abused co-twins. The contribution of familial and individual-specific factors to reported sexual abuse was also examined. METHOD: Information about lifetime psychopathology and substance use was obtained by structured telephone interviews with 5995 Australian twins. Twins who reported a history of childhood sexual abuse (CSA) were contrasted on lifetime psychopathology with subjects without such a history; in addition, comparisons were made between same-sex twin pairs discordant for CSA. RESULTS: A history of CSA was reported by 5.9% of the women and 2.5% of the men. In the sample as a whole, those reporting CSA were more likely to receive lifetime diagnoses of major depression, conduct disorder, panic disorder and alcoholism, and were more likely to report suicidal ideation and a history of suicide attempt. Abused women, but not men, were also more likely to report social phobia. When comparisons were restricted to non-abused co-twins, no differences in psychopathology were seen. However, rates of major depression, conduct disorder and suicidal ideation were higher if both co-twins were abused than if the respondent alone reported CSA. Model-fitting indicated that shared environmental factors influenced risk for reported CSA in women, but not in men. CONCLUSION: The association between CSA and psychopathology arises at least in part through the influence of shared familial factors on both risk of victimization and risk of psychopathology.

Adult↗

PubMed2000

Monoamine oxidase: associations with alcohol dependence, smoking and other measures of psychopathology.

BACKGROUND: Many reports have appeared on associations between platelet monoamine oxidase (MAO) activity and susceptibility to psychiatric conditions; principally alcohol dependence but also conduct disorder, other drug use and depression. Recently, it has become apparent that MAO activity is inhibited by some component of cigarette smoke, and smokers have low platelet MAO activity. Since the prevalence of smoking is higher in many of the conditions in which MAO has been implicated, the MAO susceptibility associations may be partly, or entirely, false. METHODS: We have measured platelet MAO in 1551 subjects, recruited from the Australian NHMRC Twin Registry, who have provided information on alcohol use and dependence, smoking, conduct disorder, depression, attempted suicide, panic disorder and social phobia. RESULTS: Current smoking reduced platelet MAO activity in a significant and dose-related manner, with no evidence of lower MAO in ex-smokers or in non-smoking subjects with co-twins who smoked. Alcohol use and lifetime DSM-III-R alcohol dependence history were not associated with MAO activity when smoking was taken into account. Depression, panic disorder and social phobia showed no significant associations with platelet MAO activity. Subjects with a history of serious attempts at suicide had low platelet MAO activity; but although the difference from controls was as great as the reduction associated with smoking it was not significant after correction for smoking effects. CONCLUSIONS: Although synaptic MAO activity undoubtedly plays a role in psychopathology, the concept that platelet MAO activity is a direct genetic marker of vulnerability to alcohol dependence cannot be sustained.

Adult↗