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.

A Transdiagnostic Approach to Understanding Eating Disorders

Categorical models dominate the eating disorder field, but the tandem use of categorical and dimensional models has been proposed. A transdiagnostic dimensional model, number of lifetime eating disorder behaviors (LEDB), was examined with respect to (1) its relationship to a variety of indicators of the individual's functioning, (2) the degree to which it was influenced by genetic and environmental risk factors, and (3) exposure to specific environmental risk factors. Data from self-report and interview from 1002 female twins (mean age = 34.91 years, SD = 2.09) were examined. While 15.4% women met criteria for a lifetime eating disorder, 29% had at least one LEDB. The dimensional measure provided an indicator of associated functioning, and was influenced primarily by the nonshared environment. The number of LEDB was associated with the degree of impaired functioning. This impairment was associated with conflict between parents and criticism from parents when growing up.

GPNN: Power studies and applications of a neural network method for detecting gene-gene interactions in studies of human disease

Background The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease. Results We show that GPNN has high power to detect even relatively small genetic effects (2–3% heritability) in simulated data models involving two and three locus interactions. The limits of detection were reached under conditions with very small heritability (

Familial aggregation of human infection with Schistosoma japonicum in the Poyang Lake region, China

Despite the success of extensive control measures that have been implemented in China for over 50 years, the number of individuals infected with Schistosoma japonicum remains high in the existing endemic areas. A variance components analysis was undertaken to estimate the heritable and environmental components that contribute to S. japonicum infection in the Poyang Lake region of Jiangxi Province, PR China. The total target population was 3148 from four separate administrative villages. Two thousand seven hundred and five of these comprised 400 families ranging in size from 3 to 188. After adjustments were made for gender, water contact and past history of having had schistosomiasis, the heritable component was estimated to account for as much as 58% of the phenotype variation under the polygenic model. Household was not shown to be an important environmental factor. Incorporating village effects indicated that the results were valid for the total population. We conclude that genetic heritability in this region is high and plays an important role in determining risk of infection with S. japonicum. (c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

GPNN: Power studies and applications of a neural network method for detecting gene-gene interactions in studies of human disease

Background: The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease. Results: We show that GPNN has high power to detect even relatively small genetic effects (2-3% heritability) in simulated data models involving two and three locus interactions. The limits of detection were reached under conditions with very small heritability (

The epidemiology and genetics of smoking initiation and persistence: Crosscultural comparisons of twin study results

We examined whether there are crosscultural differences in the magnitude of genetic and environmental contributions to risk of becoming a regular smoker and of persistence in smoking in men and women. Standard methods of epidemiologic and genetic analysis were applied to questionnaire data on history of cigarette use obtained from large samples of male and female like-sex twins from three different countries: Australia (N = 2284 pairs), Sweden (N = 8651 pairs), and Finland (N = 10,948 pairs). Samples were subdivided into three age groups (AG), 18-25 years, 26-35 years, and 36-46 years of age. The magnitude of genetic influence for lifetime smoking was found to be consistent across country and AG for women (46%) and men (57%), and estimates of the contribution from environmental influences shared by twin and co-twin could be equated across all countries by AG for the women (from youngest to oldest AG: 45%, 35%, and 26%), but not for men, with separate estimates obtained for the Scandinavian (33%, 29%, and 19%) and the Australian men (26%, 9%, and 11 %). There was no evidence for an important role for shared environmental influences on persistent smoking, and the genetic contribution was found to be consistent in magnitude in men and women, and the same across country and AG (52%). There are strong genetic influences on smoking behavior, and that risk of becoming a smoker (but not persistence in smoking) may be modified by experiences shared by twins that differ by AG and, at least for men, cultural background.

Genetic diversity among community methicillin-resistant Staphylococcus aureus strains causing outpatient infections in Australia

Increasing reports of the appearance of novel nonmultiresistant methicillin-resistant Staphylococcus aureus MRSA (MRSA) strains in the community and of the spread of hospital MRSA strains into the community are cause for public health concern. We conducted two national surveys of unique isolates of S. aureus from clinical specimens collected from nonhospitalized patients commencing in 2000 and 2002, respectively. A total of 11.7% of 2,498 isolates from 2000 and 15.4% of 2,486 isolates from 2002 were MRSA. Approximately 54% of the MRSA isolates were nonmultiresistant (resistant to less than three of nine antibiotics) in both surveys. The majority of multiresistant MRSA isolates in both surveys belonged to two strains (strains AUS-2 and AUS-3), as determined by pulsed-field gel electrophoresis (PFGE) and resistogram typing. The 3 AUS-2 isolates and 10 of the 11 AUS-3 isolates selected for multilocus sequence typing (MLST) and staphylococcal chromosomal cassette mec (SCCmec) analysis were ST239-MRSA-III (where ST is the sequence type) and thus belonged to the same clone as the eastern Australian MRSA strain of the 1980s, which spread internationally. Four predominant clones of novel nonmultiresistant MRSA were identified by PFGE, MLST, and SCCmec analysis: ST22-MRSA-IV (strain EMRSA-15), ST1-MRSA-IV (strain WA-1), ST30-MRSA-IV (strain SWP), and ST93-MRSA-IV (strain Queensland). The last three clones are associated with community acquisition. A total of 14 STs were identified in the surveys, including six unique clones of novel nonmultiresistant MRSA, namely, STs 73, 93, 129, 75, and 80sIv and a new ST. SCCmec types IV and V were present in diverse genetic backgrounds. These findings provide support for the acquisition of SCCmec by multiple lineages of S. aureus. They also confirm that both hospital and community strains of MRSA are now common in nonhospitalized patients throughout Australia.

Challenges to environmental toxicology and epidemiology: where do we stand and which way do we go?

Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today's settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene-environment interactions. For a best conduct of studies, modem toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Genetic diversity of Australian Fusarium graminearum and F-pseudograminearum

Genotypic diversity in Fusarium pseudograminearum and F. graminearum from Australia and the relationship between diversity and pathogen aggressiveness for head blight and/or crown rot of wheat were examined. Amplified fragment length polymorphism (AFLP) analysis revealed a high level of genotypic diversity within each species. Sixty-three of the 149 AFLP loci were significantly different between the two species and 70 of 72 F. pseudograminearum and 56 of 59 F. graminearum isolates had distinct haplotypes. When head blight and crown rot severity data from a recently published work on isolates representing the entire range of aggressiveness were used, only the genotypic diversity of F. pseudograminearum was significantly associated with its aggressiveness for the two diseases. Cluster analyses clearly demonstrated the polyphyletic structures that exist in both pathogen populations. The spatial diversity within F. graminearum was high within a single field, while frequent gene flow (N-m similar to 14) and a low fixation index (G(st) = 0.03) were recorded among F. pseudograminearum isolates from the adjacent states of New South Wales and Queensland. The differences in population structure between the heterothallic F. pseudograminearum (teleomorph G. coronicola) and the homothallic F. graminearum (teleomorph G. zeae) were not as pronounced as expected given their contrasting mating systems. Neither species was panmictic or strictly clonal. This points to sexual recombination in F. pseudograminearum, suggesting that ascospores of G. coronicola may also play a role in its biology and epidemiology.

Genetic uniformity of international isolates of Leifsonia xyli subsp xyli, causal agent of ratoon stunting disease of sugarcane

An international collection of the sugarcane ratoon stunting disease pathogen, Leifsonia xyli subsp. xyli, was analysed to assess genetic diversity. DNA fingerprinting using BOX primers was performed on 105 isolates, comprising 65 Australian isolates and an additional 40 isolates from Indonesia (n = 8), Japan (n = 1), USA (n = 3), Brazil (n = 2), Mali (n = 2), Zimbabwe (n = 13), South Africa (n = 9) and Reunion (n = 2). Sixty-two of these isolates were also screened using ERIC primers. No variation was found among any of the isolates. The intergenic spacer (IGS) region of the ribosomal RNA genes from 54 isolates was screened for sequence variation using single-stranded conformational polymorphism (SSCP), but none was observed. Direct sequencing of the IGS from a subset of nine isolates, representing all of the countries sampled in this study, confirmed the results of the SSCP analysis. Likewise, no sequence variation was found in the 16S ribosomal RNA genes of the same subset. Four Colombian isolates from sugarcane, morphologically similar to L. xyli subsp. xyli, were putatively shown to be an undescribed Agrococcus species of unknown pathogenicity. The lack of genetic variation among L. xyli subsp. xyli isolates, independent of time of sampling, cultivar of isolation, or country of origin, suggests the worldwide spread of a single pathogenic clone, and further suggests that sugarcane cultivars resistant to ratoon stunting disease in one area should retain this property in other regions.