Biomedical subjects

N G Martin

Publications and source records attributed to N G Martin.

At least 91 records · Page 5Linked to original sources

PubMed1999

Major depressive disorder in a community-based twin sample: are there different genetic and environmental contributions for men and women?

BACKGROUND: Depression affects more women than men and often aggregates in families. Using a community-based sample of twins, we examined the contributions of genetic and environmental factors to the risk of developing major depressive disorder and the effect of sex and different definitions of depression on the relative contributions of genetic and environmental effects. Sex differences in genetic effects were also studied. METHODS: A volunteer sample of Australian twins (2662 pairs) was interviewed using an abbreviated version of the Semi-Structured Assessment for the Genetics of Alcoholism, a semi-structured lay interview designed to assess psychiatric disorders. Depression was defined using 3 different criteria sets: DSM-III-R major depressive disorder, DSM-IV major depressive disorder, and severe DSM-IV major depressive disorder. Genetic and environmental contributions to the liability to develop depression were estimated using genetic model fitting. RESULTS: Lifetime prevalences were 31% in women and 24% in men for DSM-III-R major depressive disorder, 22% in women and 16% in men for DSM-IV major depressive disorder, and 9% in women and 3% in men for severe DSM-IV major depressive disorder. In women, the simplest model to fit the data implicated genetic factors and environmental factors unique to the individual in the development of depression, with heritability estimates ranging from 36% to 44%. In men, depression was only modestly familial, and thus individual environmental factors played a larger role in the development of depression. For DSM-III-R major depressive disorder, there were statistically different estimates for heritability for men vs. women. For both sexes, the relative contributions of genetic and environmental factors were stable using different definitions of depression. CONCLUSIONS: There was moderate familial aggregation of depression in women and this primarily was attributable to genetic factors. In men, there was only modest familial aggregation of depression. For both men and women, individual environmental experiences played a large role in the development of depression. Major depressive disorder as defined by DSM-III-R was more heritable in women as compared with men. The relative contributions of genetic and environmental factors in the development of depression were similar for varying definitions of depression, from a broad definition to a narrow definition.

Adult↗

PubMed1999

Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins.

The presence of melanocytic naevi is the strongest known risk factor for malignant melanoma. We have developed a computer imaging system with which it is possible to make quantitative measures of the size, color, and shape of pigmented lesions. The objective of this study was to examine the genetic and environmental contributions to these characteristics of naevi as measured by computer image analysis in a sample of adolescent twins. We captured video images of the 5 most atypical pigmented skin lesions (i.e., the largest, darkest, or most irregularly shaped) on each individual from 322 Australian adolescent twin pairs. Features extracted by computer image analysis for each lesion included color, size, symmetry, elongation, boundary irregularity, and edge distinctness. We found major genetic influences on the color and size of lesions accounting for between 40 and 80% of total variance. There were significant components of shared environmental influence (22-45% of total variance) for the color variables, with sun exposure the most obvious explanation. Differences between individuals in naevus color and size are largely genetic in origin although there are significant environmental contributions to color as well.

Adolescent↗

PubMed1999

Fatigue as related to anxiety and depression in a community-based sample of twins aged over 50.

Measures of fatigue, anxiety and depression were administered in self-report questionnaire format to a community-based sample of 2703 Australian twins aged over 50. Factor analysis indicated that a two-factor solution was appropriate and demonstrated a clear separation between fatigue-related items and questionnaire items relating to anxiety and depression. Highly congruent factor structures were derived for male and female subjects.

Anxiety Disorders↗

PubMed1999

Somatic distress as a distinct psychological dimension.

BACKGROUND: Somatoform disorders such as neurasthenia and chronic fatigue are characterized by a combination of prolonged fatigue and disabling neuropsychological and neuromuscular symptoms. However, the debate concerning the theoretical underpinnings of somatic disorders resembles the perennial dispute over the taxonomy of anxiety and depression. The objective of this study is to analyse the dimensional structure of items measuring anxiety, depression, phobic anxiety, somatic distress, and insomnia. It is anticipated that somatic distress should emerge as empirically distinct from measures of anxiety and depression, thereby lending support to proponents of the construct as independent of both anxiety and depression symptomatology. METHODS: A 33-item self-report symptom inventory derived from the SCL-90 and DSSI/sAD scales was used to measure recently experienced psychiatric distress in the form of depression, anxiety, phobic anxiety, somatic distress, and insomnia. SCL and DSSI/sAD items were measured on a four-point distress scale from 1 'not-at-all' to 4 'unbearably'. The inventory was administered to a community-based sample of 3468 Australian twins between the ages of 18 and 28. RESULTS: Factor analysis using Polychoric correlations and a Promax rotation criterion produced four factors: depression, phobic anxiety, somatic distress, and sleep disturbance. CONCLUSION: Results from the current factor analysis, together with the documented prevalence of somatic disorders, including evidence regarding the genetic and biological independence of somatic symptomatology, lend support to the argument that somatic symptoms, although correlated, are independent of anxiety and depression.

Adult↗

PubMed1999

Predictors of hysterectomy: an Australian study.

OBJECTIVE: We evaluated the relative importance of predictors of hysterectomy. STUDY DESIGN: A questionnaire survey of an Australia-wide sample of adult female twins was conducted; self-report data were validated against reports from treating physicians. RESULTS: A total of 3096 women (94%) and 366 physicians (87%) responded. The sensitivity of patient report of hysterectomy was 98.2%. Best predictors of hysterectomy were endometriosis (odds ratio 4.85, 95% confidence interval 3.17-7.43), medical consultation for menorrhagia (odds ratio 3.55, 95% confidence interval 2.47-5.12), joint effects of fibroids with medical consultation for chronic or persisting pelvic pain (odds ratio 3.34, 95% confidence interval 1. 42 to 7.87), having smoked >40 cigarettes per day (odds ratio 3.24, 95% confidence interval 1.10-9.55), joint effects of fibroids with consultation for menstrual problems (odds ratio 2.61, 95% confidence interval 1.36-5.01), and tubal ligation (odds ratio 1.77, 95% confidence interval 1.31-2.39). Less-important predictors were age and higher education level (protective). CONCLUSION: Consulting a physician about pelvic pain and menstrual problems, especially heavy bleeding, are recognized steps toward hysterectomy. Of particular interest for future genetic analyses are the high odds of hysterectomy for women with endometriosis, fibroids, or menorrhagia.

Adult↗

PubMed1999

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.

Adolescent↗

PubMed1999

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.

Adult↗

PubMed1999

The structure of genetic and environmental risk factors for three measures of disordered eating.

BACKGROUND: The study explored the genetic and environmental risk factors for both the behaviours and attitudes characteristic of disordered eating. METHODS: In three waves of data collection, information was collected from female twins regarding their eating and attitudes towards eating, weight and shape. The first assessment consisted of a self-report questionnaire (1988-9) with 1682 women. The second assessment consisted of a semi-structured psychiatric interview schedule (1992-3), completed by 1852 women, many of whom had completed Wave 1 assessment. The third assessment, with 325 women chosen from Waves 1 and 2 (1995-6), consisted of a semi-structured interview (the Eating Disorder Examination). RESULTS: As only one twin pair was concordant for lifetime bulimia nervosa at Wave 3 assessment, ordinal measures of all assessments were used in a multivariate genetic analysis. Results indicated that additive genetic and non-shared environmental influences best explained variance in liability to disordered eating, with about 60% (95% CI 50-68) of the variance explained by genetic factors. Comparison with a model allowing for the effects of shared environment indicated genetic factors accounted for a similar degree of variance (59%, 95% CI 36-68). CONCLUSION: Liability to the development of the behaviours and attitudes characteristic of eating disorders is best explained by both environmental and genetic factors, with covariation between the three measures best explained by a single latent phenotype of disordered eating which has a heritability of 60%.

Adult↗

PubMed1999

Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk.

BACKGROUND: Substantial evidence exists for an important genetic contribution to alcohol dependence risk in women and men. It has been suggested that genetically determined differences in alcohol sensitivity may represent one pathway by which an increase in alcohol dependence risk occurs. METHODS: Telephone interview follow-up data were obtained on twins from male, female and unlike-sex twin pairs who had participated in an alcohol challenge study in 1979-81, as well as other pairs from the same Australian twin panel surveyed by mail in 1980-82. RESULTS: At follow-up, alcohol challenge men did not differ from other male twins from the same age cohort on measures of lifetime psychopathology or drinking habits; but alcohol challenge omen were on average heavier drinkers than other women. A composite alcohol sensitivity measure, combining subjective intoxication and increase in body-sway after alcohol challenge in 1979-81, exhibited high heritability (60 %). Parental alcoholism history was weakly associated with decreased alcohol sensitivity in women, but not after adjustment for baseline drinking history, or in men. High alcohol sensitivity in men was associated with substantially reduced alcohol dependence risk (OR = 0.05, 95% CI 0.01-0.39). Furthermore, significantly decreased (i.e. low) alcohol sensitivity was observed in non-alcoholic males whose MZ co-twin had a history of alcohol dependence, compared to other non-alcoholics. These associations remained significant in conservative analyses that controlled for respondents' alcohol consumption levels and alcohol problems in 1979-81. CONCLUSIONS: Men (but not women) at increased genetic risk of alcohol dependence (assessed by MZ co-twin's history of alcohol dependence) exhibited reduced alcohol sensitivity. Associations with parental alcoholism were inconsistent.

Adult↗

PubMed1999

How accurate is the family history method for assessing siblings' sexual orientation?

Previous studies investigating the familial nature of sexual orientation have often relied on the reports of siblings. They have generally obtained extremely high accuracy rates for proband rating of the sexual orientation of siblings. However, participants in these studies have probably been unusually open about their sexual orientation, and thus it is uncertain if more representative participants would have as accurate knowledge about their families. An unselected sample of twins from the Australian Twin Registry rated their own, their cotwins', and their siblings' sexual orientations. We examined accuracy of heterosexual and homosexual probands' assessments of their twins' sexual orientations, as well as cotwins' agreement about other siblings' orientations. Concordance between twins' ratings of their cotwins' orientations with the cotwins' self-rated orientations was considerably lower than that found in previous studies, as was the level of agreement between members of a twin pair in the assessment of other siblings' sexual orientations. Marital history as a proxy variable for determining the sexual orientation of older subjects did not support its use with women, though its use for older men received some weak support.

Adult↗

PubMed1999

A genetic analysis of the eating and attitudes associated with bulimia nervosa: dealing with the problem of ascertainment in twin studies.

Little is known about the etiology of bulimia nervosa and the attitudes associated with it. We have undertaken a study of selected (45 pairs) and unselected (106 pairs) female twins to elucidate the broad causes of individual differences in these behaviours and attitudes. The selected sample was chosen on the basis of at least one of the twin pair having a lifetime incidence of bulimia nervosa. Biometrical model fitting, which corrected for the biased twin correlations of the ascertained group, was used to investigate the genetic and environmental risk factors contributing to the development of bulimia nervosa. The best-fitting model showed that individual variation was best explained by additive genetic influences (62%) and nonshared environmental influences (38%). The proportion of genetic variance affecting individual variation in the ascertained group and the random group was not found to be significantly different. In summary, it is suggested that it may not be necessary to supplement a randomly selected sample with an ascertained sample when investigating the liability to a low-prevalence psychiatric disorder if a continuous measure of that disorder is available.

Adult↗

PubMed1999

Genetic and social determinants of initiation and age at onset of smoking in Australian twins.

Retrospective data on age at onset of smoking, reported by 3810 adult Australian twin pairs, were analyzed to determine the role of genetic and environmental factors in the onset of smoking. Results of nonmetric multidimensional scaling supported a two-process model in which different etiologic factors determined which individuals were at risk of becoming smokers and the age at onset of smoking in those who were at risk. Parametric model-fitting confirmed this difference. For female twins and younger male twins (aged 30 years or less), the onset of smoking was strongly influenced by genetic factors, with shared and nonshared environmental effects having a more modest impact. For older male twins, shared environmental influences on onset of smoking were very important, and the influence of genetic predisposition was slight. The age at which smoking onset occurred, however, was influenced by both genetic and nonshared environmental effects, but not by shared environmental effects, in both sexes and both cohorts.

Adolescent↗

PubMed1999

The genetics of smoking persistence in men and women: a multicultural study.

Using a correlated liability dimensions model, we examined the extent to which the same genetic and environmental factors influence both initiation of regular cigarette smoking and maintenance of the smoking habit in men and women. We analyzed questionnaire survey data obtained from large samples of male and female like-sexed twins from three countries, Australia (N = 1535 pairs), Sweden (N = 5916 pairs), and Finland (N = 4438 pairs), subdivided into three age bands (18-25, 26-35, and 36-46 years of age). We found that familial influences on risk for persistence in smoking cannot be entirely explained by the same factors responsible for risk of smoking initiation. Total genetic variance for smoking persistence varied little by age band and sex (range, 39-49% in women and 42-45% in men); however, even among twins in the youngest group (18-25 years of age), who on average have the fewest years of cigarette use, less than 40% of the total genetic variance in smoking persistence was accounted for by the same genetic factors that increased risk of smoking initiation, and this percentage decreased to less than 10% in the 36-46 year olds.

Adolescent↗

PubMed1999

An assessment of the genetic relationship between alcohol metabolism and alcoholism risk in Australian twins of European ancestry.

The present analyses examined genetic influences on alcohol metabolism and their possible relationship to risk of alcohol dependence. Subjects were 206 Australian twin pairs who participated in an alcohol challenge protocol in 1979-1981, in which they were given a 0.75 g/kg dose of alcohol; blood alcohol concentrations (BACs) measured at five times over a 3-hr period after alcohol ingestion were examined. Structural equation modeling, fitting a combined autoregressive and common factor model, indicated significant heritabilities for both men and women (h2 range = 0.19-0.71), with significant parameter heterogeneity as a function of gender. In 1992-1993, both twins from 159 of the alcohol challenge pairs completed a telephone-administered psychiatric diagnostic interview. Repeated-measures MANOVAs were used to examine whether respondent's or cotwin's DSM-III-R alcohol dependence status, or parental history of alcohol problems, was associated with variation in alcohol metabolism. There was some evidence that individuals at increased genetic risk of alcohol dependence [with either a paternal history of alcohol problems (women) or an MZ male cotwin who reported a history of alcohol dependence by 1992-1993] showed lower initial BACs than other groups. However, this effect was not seen in those who themselves had a history of alcohol dependence by interview follow-up, perhaps because this relationship was already masked by a history of excessive drinking at baseline.

Adult↗

PubMed1999

A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs.

Important risk factors for melanoma are densely clustered melanocytic nevi (common moles) and mutations in the p16 (CDKN2A) gene. Nevi may be subclassified as raised or flat. In our sample, raised nevi were 27% of the total, and the two kinds had a correlation of.33. Correlations for total-nevus count (TNC) in 153 MZ and 199 DZ twin pairs were.94 and.60, respectively, which are compatible with a very-high degree of genetic determination. We hypothesized that some of the genetic variance might be due to variation in the p16 gene. Analysis of linkage to a highly polymorphic marker (D9S942), located close to p16, detected quantitative-trait-loci (QTL) effects accounting for 27% of variance in TNC, rising to 33% if flat but not raised moles were considered. Total heritability was higher for raised (.69) than for flat (.42) moles, but QTL linkage was 0 for raised moles, whereas it accounted for 80% of the heritability of flat moles; additionally, family environment accounted for only 15% of variance in raised versus 46% in flat moles. These findings suggest that raised and flat nevi have very different etiologies. Longer alleles at D9S942 were associated with higher flat-mole counts, and a novel modification to a within-sibship association test showed that this association is genuine and not due to population stratification, although it accounts for only 1% of total variance. Since germline mutations in the exons of CDKN2A are rare, it is likely that variants in the noncoding regions of this gene, or in another gene nearby, are responsible for this major determinant of moliness and, hence, of melanoma risk.

Child↗

PubMed1999

Genetic and environmental causes of variation in basal levels of blood cells.

The genetic and environmental determinants of variation in blood cell size and number were investigated in 392 pairs of 12-year-old twins. The following blood cell indices were measured: haemoglobin, red blood cell count, haematocrit, mean corpuscular volume, platelet number, total white cell count, level of neutrophils, monocytes, eosinophils, total lymphocytes, CD3+ lymphocytes, CD4+ lymphocytes, CD8+ lymphocytes, CD19+ lymphocytes, CD56+ lymphocytes and CD4+/CD8+ ratio. Genetic factors contributed significantly to all blood cell measures accounting for between 61 and 96% of variance. Heritability estimates did not differ significantly between males and females, although the sample size of the present study was not large enough to exclude the possibility of sex-limited gene expression. Common environmental factors were important in determining red blood cell count and haematocrit, but were not important in determining basal levels of any white blood cell type.

Antigens, CD↗

PubMed1999

Self-transcendence as a measure of spirituality in a sample of older Australian twins.

Measures of self-transcendence, physical health and psychological well-being were included in a self-report Health and Lifestyle questionnaire administered to Australian twins aged over 50 between 1993 and 1995. Self-transcendence appears to be higher among older Australian women than men, and was significantly associated with religious affiliation, marital status (in women) and age (in men). No strong correlations were observed between self-transcendence and any measure of psychological or physical health. Additive genetic effects were found to be important in influencing self-transcendence, with heritability estimates of 0.37 and 0.41 for men and women respectively, whilst shared environment effects were not found to be significant. Multivariate modelling of self-transcendence scores and self-reported church attendance behavior indicated substantially different etiologies for these variables, with implications for methods of investigation of religiosity and spirituality.

Age Factors↗

PubMed1999

Frequency of church attendance in Australia and the United States: models of family resemblance.

Data on frequency of church attendance have been obtained from separate cohorts of twins and their families from the USA and Australia (29,063 and 20,714 individuals from 5670 and 5615 families, respectively). The United States sample displayed considerably higher frequency of attendance at church services. Sources of family resemblance for this trait also differed between the Australian and US data, but both indicated significant additive genetic and shared environment effects on church attendance, with minor contributions from twin environment, assortative mating and parent-offspring environmental transmission. Principal differences between the populations were in greater maternal environmental effects in the US sample, as opposed to paternal effects in the Australian sample, and smaller shared environment effects observed for both women and men in the US cohort.

Adult↗