Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Identification of seven loci affecting mean telomere length and their association with disease

Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 x 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10−61) than father–offspring correlation (r=0.33; P-value=7.01 × 10−5), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10−5). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10−30) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10−23) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10−10). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.

A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications

BACKGROUND Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. METHODS Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. RESULTS No findings reached genome-wide significance (p = 8.4 x 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 x 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. CONCLUSIONS We conclude that: - 1) meta-analyses of consumption data may contribute usefully to gene discovery; - 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging, and; - 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies).

Using wheat flour in the production of organic banana prawns

Banana prawn (Fenneropenaeus merguiensis) juveniles (1-2 g) were compared for survival, growth and condition after feeding in tanks over one month with several simple diets based on organically certified whole wheat flour. All feeds were applied once per day at 6% of the starting body weight, and produced high survival (>94%). A commercial Australian prawn feed used as the control diet produced the highest (P<0.05) growth (101% weight gain) and condition measured as the length of antennae (13.2 cm). The unfed control had significantly (P<0.05) lower survival (56%), and resulted in a weight loss (3.1%) and the shortest antennae (9.4 cm). Adding free flour to tanks produced lower (P<0.05) growth (6.9%) and shorter (P<0.05) antennae (10.3 cm) than adding pelletised flour with low levels (dry weight) of additional nutritional substances and feed attractants (chicken’s whole egg: 1.5%, polychaete slurry: 1.1% and 6.8%, molasses: 4.2%). Rolling the flour into a dough ball also appeared to marginally improve its direct utilisation by the prawns. These results are considered within the context of appropriate nutrition for Penaeids and successfully producing certified organic prawns in Australia.

Wet season resting - economic insights from scenario modelling

Pasture degradation, particularly that attributable to overgrazing, is a significant problem across the northern Australian rangelands. Although grazing studies have identified the scope for wet season resting strategies to be used to rehabilitate degraded pastures, the economic outcome of these strategies has not been extensively demonstrated. An exploratory study of the prospective economic value of wet season resting is presented using an economic simulation model of a 28000 ha beef enterprise located in the Charters Towers region of north-eastern Australia to explore seven hypothetical scenarios centred on the projected performance of a wet season resting strategy. A series of 20-year simulations for a range of pasture recovery profiles, stocking capacity, animal productivity responses, beef prices and agistment options are compared with a baseline scenario of taking no action. Estimates of the net present value of the 20-year difference in total enterprise gross margins between the various resting options and the 'do nothing' option identify that wet season resting can offer a positive economic return for the range of scenarios examined, although this is contingent on the assumptions that are made concerning the trajectories of change in carrying capacity and animal productivity. Some implications for management and policy making to support the practical implementation of wet season resting strategies are discussed.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

The discovery of genetic factors that contribute to schizophrenia susceptibility is a key challenge in understanding the etiology of this disease. Here, we report the identification of a novel schizophrenia candidate gene on chromosome 1q32, plexin A2 (PLXNA2), in a genome-wide association study using 320 patients with schizophrenia of European descent and 325 matched controls. Over 25,000 single-nucleotide polymorphisms (SNPs) located within approximately 14,000 genes were tested. Out of 62 markers found to be associated with disease status, the most consistent finding was observed for a candidate locus on chromosome 1q32. The marker SNP rs752016 showed suggestive association with schizophrenia (odds ratio (OR) = 1.49, P = 0.006). This result was confirmed in an independent case-control sample of European Americans (combined OR = 1.38, P = 0.035) and similar genetic effects were observed in smaller subsets of Latin Americans (OR = 1.26) and Asian Americans (OR = 1.37). Supporting evidence was also obtained from two family-based collections, one of which reached statistical significance (OR = 2.2, P = 0.02). High-density SNP mapping showed that the region of association spans approximately 60 kb of the PLXNA2 gene. Eight out of 14 SNPs genotyped showed statistically significant differences between cases and controls. These results are in accordance with previous genetic findings that identified chromosome 1q32 as a candidate region for schizophrenia. PLXNA2 is a member of the transmembrane semaphorin receptor family that is involved in axonal guidance during development and may modulate neuronal plasticity and regeneration. The PLXNA2 ligand semaphorin 3A has been shown to be upregulated in the cerebellum of individuals with schizophrenia. These observations, together with the genetic results, make PLXNA2 a likely candidate for the 1q32 schizophrenia susceptibility locus.

Zygosity diagnosis in the absence of genotypic data: An approach using latent class analysis

For zygosity diagnosis in the absence of genotypic data, or in the recruitment phase of a twin study where only single twins from same-sex pairs are being screened, or to provide a test for sample duplication leading to the false identification of a dizygotic pair as monozygotic, the appropriate analysis of respondents' answers to questions about zygosity is critical. Using data from a young adult Australian twin cohort (N = 2094 complete pairs and 519 singleton twins from same-sex pairs with complete responses to all zygosity items), we show that application of latent class analysis (LCA), fitting a 2-class model, yields results that show good concordance with traditional methods of zygosity diagnosis, but with certain important advantages. These include the ability, in many cases, to assign zygosity with specified probability on the basis of responses of a single informant (advantageous when one zygosity type is being oversampled); and the ability to quantify the probability of misassignment of zygosity, allowing prioritization of cases for genotyping as well as identification of cases of probable laboratory error. Out of 242 twins (from 121 like-sex pairs) where genotypic data were available for zygosity confirmation, only a single case was identified of incorrect zygosity assignment by the latent class algorithm. Zygosity assignment for that single case was identified by the LCA as uncertain (probability of being a monozygotic twin only 76%), and the co-twin's responses clearly identified the pair as dizygotic (probability of being dizygotic 100%). In the absence of genotypic data, or as a safeguard against sample duplication, application of LCA for zygosity assignment or confirmation is strongly recommended.

Nitrogen leaching from the root zone of sugarcane and bananas in the humid tropics of Australia

Loss of nitrogen in deep drainage from agriculture is an important issue for environmental and economic reasons, but limited field data is available for tropical crops. In this study, nitrogen (N) loads leaving the root zone of two major humid tropical crops in Australia, sugarcane and bananas, were measured. The two field sites, 57 km apart, had a similar soil type (a well drained Dermosol) and rainfall (∼2700 mm year -1) but contrasting crops and management. A sugarcane crop in a commercial field received 136-148 kg N ha -1 year -1 applied in one application each year and was monitored for 3 years (first to third ratoon crops). N treatments of 0-600 kg ha -1 year -1 were applied to a plant and following ratoon crop of bananas. N was applied as urea throughout the growing season in irrigation water through mini-sprinklers. Low-suction lysimeters were installed at a depth of 1 m under both crops to monitor loads of N in deep drainage. Drainage at 1 m depth in the sugarcane crops was 22-37% of rainfall. Under bananas, drainage in the row was 65% of rainfall plus irrigation for the plant crop, and 37% for the ratoon. Nitrogen leaching loads were low under sugarcane (<1-9 kg ha -1 year -1) possibly reflecting the N fertiliser applications being reasonably matched to crop requirements and at least 26 days between fertiliser application and deep drainage. Under bananas, there were large loads of N in deep drainage when N application rates were in excess of plant demand, even when applied fortnightly. The deep drainage loss of N attributable to N fertiliser, calculated by subtracting the loss from unfertilised plots, was 246 and 641 kg ha -1 over 2 crop cycles, which was equivalent to 37 and 63% of the fertiliser application for treatments receiving 710 and 1065 kg ha -1, respectively. Those rates of fertiliser application resulted in soil acidification to a depth of 0.6 m by as much as 0.6 of a unit at 0.1-0.2 m depth. The higher leaching losses from bananas indicated that they should be a priority for improved N management. Crown Copyright © 2012.

Integrating organic matter into banana plantation in North Queensland: the effects on soil properties

The major banana production areas in Australia are particularly sensitive to environments due to their close proximity to areas of World Heritage rainforest and the Great Barrier Reef catchment. Management of soil quality, nutrients and pesticides are vital to maintaining the integrity of these sensitive areas. Studies on cropping systems have suggested that integrating organic matter into ground cover management would improve the quality of soil under banana cultivation. In this study, an alternative management practice for bananas, which addresses the management of organic matter and fertiliser application, was assessed and compared to the conventional practice currently employed in the banana industry. Several chemical, physical and biological soil parameters were measured including: pH, electrical conductivity, water stable aggregates, bulk density, water filled pore space, porosity, water content, fluorescein diacetate hydrolyis (FDA) and beta-glucosidase activity. The alternative management practice did not have a significant impact of the production and growth of bananas but overall improved the quality of the soil. Although some differences were observed, the chemical and physical soil characteristics did not differ dramatically between the two management systems. The addition of organic matter resulted in the soil under alternative practice having higher FDA and beta-glucosidase levels, indicating higher microbial activity. The integration of organic matter into the management of bananas resulted in positive benefits on soil properties under bananas, however, methods of maintaining organic matter in the soil need to be further researched.

On-farm Campylobacter and Escherichia coli in commercial broiler chickens: Re-used bedding does not influence Campylobacter emergence and levels across sequential farming cycles

Limitations in quality bedding material have resulted in the growing need to re-use litter during broiler farming in some countries, which can be of concern from a food-safety perspective. The aim of this study was to compare the Campylobacter levels in ceca and litter across three litter treatments under commercial farming conditions. The litter treatments were (a) the use of new litter after each farming cycle; (b) an Australian partial litter re-use practice; and (c) a full litter re-use practice. The study was carried out on two farms over two years (Farm 1, from 2009–2010 and Farm 2, from 2010–2011), across three sheds (35,000 to 40,000 chickens/shed) on each farm, adopting three different litter treatments across six commercial cycles. A random sampling design was adopted to test litter and ceca for Campylobacter and Escherichia coli, prior to commercial first thin-out and final pick-up. Campylobacter levels varied little across litter practices and farming cycles on each farm and were in the range of log 8.0–9.0 CFU/g in ceca and log 4.0–6.0 MPN/g for litter. Similarly the E. coli in ceca were ∼log 7.0 CFU/g. At first thin-out and final pick-up, the statistical analysis for both litter and ceca showed that the three-way interaction (treatments by farms by times) was highly significant (P < 0.01), indicating that the patterns of Campylobacter emergence/presence across time vary between the farms, cycles and pickups. The emergence and levels of both organisms were not influenced by litter treatments across the six farming cycles on both farms. Either C. jejuni or C. coli could be the dominant species across litter and ceca, and this phenomenon could not be attributed to specific litter treatments. Irrespective of the litter treatments in place, cycle 2 on Farm 2 remained campylobacter-free. These outcomes suggest that litter treatments did not directly influence the time of emergence and levels of Campylobacter and E. coli during commercial farming.

The Wieruszowski ancestry : from the mid 1700’s to the late 1900’s /

Family trees of the descendants of the Wieruszowski and of the Apt families from the mid 1700’s to the late 1900’s, from family sources and from other places.

Literacy, security, governmentality: Defining spaces, managing populations – How has education become part of whole of government security strategy?

In this paper I conduct a Foucauldian discourse analysis of a political speech given by Brendon Nelson in 2006 when the Australian Minister for Defence in the Howard Coalition Government. The speech connects conceptualisations of terror, globalization, education and literacy as part of a whole of government security strategy. The analysis examines this speech as an example of a liberal way of governing the conduct of diverse and unpredictable populations. My analysis suggests that the apparatus of government has been strategically used in order to biopolitically contain the rise of complex social forces and protect a set of homogenous cultural values. The purposes of education and uses of literacy are seen as instruments for the inscription of a coded set of values understood to be synonymous with civil society.