Genetic analyses of DSM-IV nicotine withdrawal in adult twins

Background. We examined whether there are genetic influences on nicotine withdrawal. and whether there are genetic factors specific to nicotine withdrawal, after controlling for factors responsible for risk of progression beyond experimentation with cigarettes and for quantity smoked (average number of cigarettes per day at peak lifetime use). Method. Epidemiologic and genetic analyses were conducted using telephone diagnostic interview data from Young adult Australian twins reporting any cigarette use (3026 women. 2553 men: mean age 30 years). Results. Genetic analysis of the eight symptoms of DSM-IV nicotine withdrawal suggests heritability is intermediate for most symptoms (26-43%). and Similar in men and women. The exceptions were depressed mood upon withdrawal. which had stronger additive genetic influences in men (53%) compared to worrien (29%). and decreased heart rate. which had low heritability (9%). Although prevalence rates were substantlally lower for DSM-IV nicotine withdrawal syndrome (15-9%), which requires impairment. than for the DSM-IV nicotine dependence withdrawal criterion (43.6%), heritability was similar for both measures: as high as 47%. Genetic modeling of smoking more than 1 or 2 cigarettes lifetime ('progression'). qualtity smoked and nicotine withdrawal found significant genetic overlap across all three components of nicotine use/dependence (genetic correlations = 0.53-0.76). Controlling for factors associated with risk of cigarette smoking beyond experimentation and quantity smoked, evidence for genetic influences specific to nicotine withdrawal (up to 23% of total variance) remained. Conclusions. Our results suggest that at least some individuals become 'hooked' or progress in the smoking habit, in part, because of it vulnerability to nicotine withdrawal.

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society UHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2) =0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine. (C) 2004 Wiley-Liss, Inc.

Defining nicotine dependence for genetic research: evidence from Australian twins

Background. Whether current criteria used to define nicotine dependence are informative for genetic research is an important empirical question. The authors used items of the DSM-IV and of the Heaviness of Smoking Index to characterize the nicotine dependence phenotype and to identify salient symptoms in a genetically informative community sample of Australian young adult female and mate twins. Method. Phenotypic and genetic factor analyses were performed on nine dependence symptoms (the seven DSM-IV substance dependence criteria and the two Heaviness of Smoking Index (HSI) items derived from the Fagerstrom Tolerance Questionnaire, time to first cigarette in the morning and number of cigarettes smoked per day). Phenotypic and genetic analyses were restricted to ever smokers. Results. Phenotypic nicotine dependence symptom covariation was best captured by two factors with a similar pattern of factor loadings for women and men. In genetic factor analysis item covariation was best captured by two genetic but one shared environmental factor for both women and men; however, item factor loadings differed by gender. All nicotine dependence symptoms were substantially heritable, except for the DSM-IV criterion of 'giving up or reducing important activities in order to smoke', which was weakly familial. Conclusions. The salient behavioral indices of nicotine dependence are similar for women and men. DSM-IV criteria of tolerance, withdrawal, and experiencing difficulty quitting and HSI items time to first cigarette in the morning and number of cigarettes smoked per day may represent the most highly heritable symptoms of nicotine dependence for both women and men.

Genetic and environmental influences on extreme personality dispositions in adolescent female twins

Background: The objective was to determine whether the pattern of environmental and genetic influences on deviant personality scores differs from that observed for the normative range of personality, comparing results in adolescent and adult female twins. Methods: A sample of 2,796 female adolescent twins ascertained from birth records provided Junior Eysenck Personality Questionnaire data. The average age of the sample was 17.0 years ( S. D. 2.3). Genetic analyses of continuous and extreme personality scores were conducted. Results were compared for 3,178 adult female twins. Results: Genetic analysis of continuous traits in adolescent female twins were similar to findings in adult female twins, with genetic influences accounting for between 37% and 44% of the variance in Extraversion (Ex), Neuroticism (N), and Social Non-Conformity (SNC), with significant evidence of shared environmental influences (19%) found only for SNC in the adult female twins. Analyses of extreme personality characteristics, defined categorically, in the adolescent data and replicated in the adult female data, yielded estimates for high N and high SNC that deviated substantially (p < .05) from those obtained in the continuous trait analyses, and provided suggestive evidence that shared family environment may play a more important role in determining personality deviance than has been previously found when personality is viewed continuously. However, multiple-threshold models that assumed the same genetic and environmental determinants of both normative range variation and extreme scores gave acceptable fits for each personality dimension. Conclusions: The hypothesis of differences in genetic or environmental factors responsible for N and SNC among female twins with scores in the extreme versus normative ranges was partially supported, but not for Ex.

A possible smoking susceptibility locus on chromosome 11p12: Evidence from sex-limitation linkage analyses in a sample of Australian twin families

Many twin studies have identified sex differences in the influence of genetic and environmental factors on smoking behaviors. We explore the evidence for sex differences for smoking initiation and cigarette consumption in a sample of Australian twin families, and extend these models to incorporate sex differences in linkage analyses for these traits. We further examine the impact of including or excluding non-smokers in genetic analyses of tobacco consumption. Accounting for sex differences improved linkage results in some instances. We identified one region suggestive of linkage on chromosome 11p12. This locus, as well as another region identified on chromosome 6p12, replicates regions identified in previous studies.

Dissecting the complex genetic basis of mate choice

The genetic analysis of mate choice is fraught with difficulties. Males produce complex signals and displays that can consist of a combination of acoustic, visual, chemical and behavioural phenotypes. Furthermore, female preferences for these male traits are notoriously difficult to quantify. During mate choice, genes not only affect the phenotypes of the individual they are in, but can influence the expression of traits in other individuals. How can genetic analyses be conducted to encompass this complexity? Tighter integration of classical quantitative genetic approaches with modern genomic technologies promises to advance our understanding of the complex genetic basis of mate choice.

Empirical Evaluation of the Genetic Similarity of Samples From Twin Registries in Australia and the Netherlands Using 359 STRP Markers

One way to achieve the large sample sizes required for genetic studies of complex traits is to combine samples collected by different groups. It is not often clear, however, whether this practice is reasonable from a genetic perspective. To assess the comparability of samples from the Australian and the Netherlands twin studies, we estimated F,, (the proportion of total genetic variability attributable to genetic differences between cohorts) based on 359 short tandem repeat polymorphisms in 1068 individuals. IF,, was estimated to be 0.30% between the Australian and the Netherlands cohorts, a smaller value than between many European groups. We conclude that it is reasonable to combine the Australian and the Netherlands samples for joint genetic analyses.

Phylogeography of an east Australian wet-forest bird, the satin bowerbird (Ptilonorhynchus violaceus), derived from mtDNA, and its relationship to morphology

Australian wet forests have undergone a contraction in range since the mid-Tertiary, resulting in a fragmented distribution along the east Australian coast incorporating several biogeographical barriers. Variation in mitochondrial DNA and morphology within the satin bowerbird was used to examine biogeographical structure throughout almost the entire geographical extent of these wet forest fragments. We used several genetic analysis techniques, nested clade and barrier analyses, that use patterns inherent in the data to describe the spatial structuring. We also examined the validity of the two previously described satin bowerbird subspecies that are separated by well-defined biogeographical barriers and tested existing hypotheses that propose divergence occurs within each subspecies across two other barriers, the Black Mountain corridor and the Hunter Valley. Our data showed that the two subspecies were genetically and morphologically divergent. The northern subspecies, found in the Wet Tropics region of Queensland, showed little divergence across the Black Mountain corridor, a barrier found to be significant in other Wet Tropics species. Biogeographical structure was found through southeastern Australia; three geographically isolated populations showed genetic differentiation, although minimal divergence was found across the proposed Hunter Valley barrier. A novel barrier was found separating inland and coastal populations in southern New South Wales. Little morphological divergence was observed within subspecies, bar a trend for birds to be larger in the more southerly parts of the species' range. The results from both novel and well-established genetic analyses were similar, providing greater confidence in the conclusions about spatial divergence and supporting the validity of these new techniques.

Duration of cannabis use - a novel phenotype?

Although cannabis is the most commonly used illicit drug, duration of cannabis use is typically short, with many of those who initiate cannabis use ceasing use by their late twenties. In this paper we analyze data from a volunteer Australian cohort of 6265 male and female twins to examine whether the duration of cannabis use is an informative phenotype for future genetic analyses. Genetic modeling indicated: (a) moderate genetic influences on duration of cannabis use in both males (41%; 95% CI = 31–51) and females (55%; 95% CI = 46–63); (b) strong genetic influences on cannabis dependence in both males (72%, 95% CI = 61–81) and females (62%, 95% CI = 48–74); (c) no evidence of shared environmental influences on duration of cannabis use or on cannabis dependence in either males or females. Importantly, this model fitting indicated that a substantial component of genetic influences (rg = .90, 95% CI = .77–.99 (males); .70, 95% CI = .57–.83 (females)) on duration of cannabis use was shared with those influencing liability to cannabis dependence. While there were high genetic correlations in both women and men, lifetime duration of cannabis may be uniquely informative in assessing components of liability to cannabis use.

Fine-scale spatial genetic correlation analyses reveal strong female philopatry within a brush-tailed rock-wallaby colony in southeast Queensland

We combine spatial data on home ranges of individuals and microsatellite markers to examine patterns of fine-scale spatial genetic structure and dispersal within a brush-tailed rock-wallaby (Petrogale penicillata) colony at Hurdle Creek Valley, Queensland. Brush-tailed rock-wallabies were once abundant and widespread throughout the rocky terrain of southeastern Australia; however, populations are nearly extinct in the south of their range and in decline elsewhere. We use pairwise relatedness measures and a recent multilocus spatial autocorrelation analysis to test the hypotheses that in this species, within-colony dispersal is male-biased and that female philopatry results in spatial clusters of related females within the colony. We provide clear evidence for strong female philopatry and male-biased dispersal within this rock-wallaby colony. There was a strong, significant negative correlation between pairwise relatedness and geographical distance of individual females along only 800 m of cliff line. Spatial genetic autocorrelation analyses showed significant positive correlation for females in close proximity to each other and revealed a genetic neighbourhood size of only 600 m for females. Our study is the first to report on the fine-scale spatial genetic structure within a rock-wallaby colony and we provide the first robust evidence for strong female philopatry and spatial clustering of related females within this taxon. We discuss the ecological and conservation implications of our findings for rock-wallabies, as well as the importance of fine-scale spatial genetic patterns in studies of dispersal behaviour.

Why are there so few genetic markers available for coral population analyses?

Coral reefs are in serious decline, and research in support of reef management objectives is urgently needed. Reef connectivity analyses have been highlighted as one of the major future research avenues necessary for implementing effective management initiatives for coral reefs. Despite the number of new molecular genetic tools and the wealth of information that is now available for population-level processes in many marine disciplines, scleractinian coral population genetic information remains surprisingly limited. Here we examine the technical problems and approaches used, address the reasons contributing to this delay in understanding, and discuss the future of coral population marker development. Considerable resources are needed to target the immediate development of an array of relevant genetic markers coupled with the rapid production of management focused data in order to help conserve our globally threatened coral reef resources.

Genetic variation of the scleractinian coral Stylophora pistillata, from western Pacific reefs

Most scleractinian coral species are widely distributed across the tropical and subtropical Indo-Pacific. However, the genetic connectivity between populations of corals separated by large distances (thousands of kilometers) is not well known. We analyzed variability in the nucleotide sequence of the internal transcribed spacer-1 (ITS-1) of the nuclear ribosomal gene unit in the ubiquitous coral Stylophora pistillata, across the western Pacific Ocean. Eight populations from Japan, Malaysia, and the northern and southern Great Barrier Reef (GBR) were studied. Phylogenetic analyses and analysis of molecular variance (AMOVA) clearly revealed that there is panmixia among these coral populations. AMOVA showed that ITS-1 sequence variability was greater within populations (78.37%) than among populations (12.06%). These patterns strongly suggest high levels of connectivity across the species' latitudinal distribution range in the western Pacific, as is seen in many marine invertebrates.

Genetic covariation of pelvic organ and elbow mobility in twins and their sisters

A range of environmental risk factors, with childbirth the most notable, have been associated with the development of pelvic organ prolapse and urinary incontinence. However, indications of genetic influence (positive family histories, ethnic differences) have prompted research into the heritability of measures of pelvic organ descent and joint mobility, which have also been associated with prolapse and incontinence. Genes appear to influence about half of the variation in these measures and, furthermore, the pelvic organ measures are associated with elbow hyperextension at a phenotypic level (r approximate to .2). We examined these measures in young, nulligravid women to determine if their association is due to a common genetic source. Data were collected from 178 Caucasian female co-twins and non-twin sisters, 50 of whom returned to be retested, which allowed reliability to be estimated and unreliable variance to be isolated in the multivariate analyses. Structural equation modeling was used to estimate genetic associations between latent elbow and bladder mobility factors for which heritabilities were estimated to be 0.80 and 0.64 respectively. The association between these factors appeared to be mediated by common genes (genetic r = .48, non-shared environmental r = -.06), with genes influencing latent elbow mobility accounting for 14% of the variation in latent bladder mobility. We speculate that genes influencing connective tissue structure may underlie this association.

Genetic Epidemiology of Alcohol-Induced Blackouts

Background: Alcohol-induced blackouts (ie, periods of anterograde amnesia) have received limited recent research attention. Objective: To examine the genetic epidemiology of lifetime blackouts and having had 3 or more blackouts in a year, including analyses controlling for the frequency of intoxication. Design, Setting, and Participants: Members of the young adult Australian Twin Register, a volunteer twin panel born between January 1, 1964, and December 3 1, 1971, were initially registered with the panel as children by their parents between 1980 and 1982. They underwent structured psychiatric telephone inter-views from February 1996 through September 2000. The current sample contains 2324 monozygotic and dizygotic twin pairs (mean [SDI age 29.9 [2.5] years) for whom both twins' responses were coded for blackout questions and for frequency of intoxication. Main Outcome Measure: Data on lifetime blackouts and having had 3 or more blackouts in a year were collected within an examination of the genetic epidemiology of alcoholism. Results: A lifetime history of blackouts was reported by 39.3% of women and 52.4% of men; 11.4% of women and 20.9% of men reported having had 3 or more blackouts in a year. The heritability of lifetime blackouts was 52.5% and that of having had 3 or more blackouts in a year was 57.8%. Models that controlled for frequency of intoxication found evidence of substantial genetic contribution unique to risk for the blackouts and a significant component of genetic risk shared with frequency of intoxication. Conclusions: The finding of a substantial genetic contribution to liability for alcohol-induced blackouts including a component of genetic loading shared with frequency of intoxication may offer important additional avenues to investigate susceptibility to alcohol-related problems.

Genetic diversity and population structure of Tasmanian devils, the largest marsupial carnivore

Genetic diversity and population structure were investigated across the core range of Tasmanian devils (Sarcophilus laniarius; Dasyuridae), a wide-ranging marsupial carnivore restricted to the island of Tasmania. Heterozygosity (0.386-0.467) and allelic diversity (2.7-3.3) were low in all subpopulations and allelic size ranges were small and almost continuous, consistent with a founder effect. Island effects and repeated periods of low population density may also have contributed to the low variation. Within continuous habitat, gene flow appears extensive up to 50 km (high assignment rates to source or close neighbour populations; nonsignificant values of pairwise F-ST), in agreement with movement data. At larger scales (150-250 km), gene flow is reduced (significant pairwise F-ST) but there is no evidence for isolation by distance. The most substantial genetic structuring was observed for comparisons spanning unsuitable habitat, implying limited dispersal of devils between the well-connected, eastern populations and a smaller northwestern population. The genetic distinctiveness of the northwestern population was reflected in all analyses: unique alleles; multivariate analyses of gene frequency (multidimensional scaling, minimum spanning tree, nearest neighbour); high self-assignment (95%); two distinct populations for Tasmania were detected in isolation by distance and in Bayesian model-based clustering analyses. Marsupial carnivores appear to have stronger population subdivisions than their placental counterparts.