Male eating disorders and related traits : Genetic epidemiological study in Finnish twins

The aim of this study was to deepen the understanding of eating disorders, body image dissatisfaction and related traits in males by examining the epidemiology and genetic epidemiology of these conditions in representative population-based twin samples. The sample of Study I included adolescent twins from FinnTwin12 cohorts born 1983 87 and assessed by a questionnaire at ages 14 y (N=2070 boys, N=2062 girls) and 17 y (N=1857 boys, N=1984 girls). Samples of Studies II-V consisted of young adult twins born 1974-79 from FinnTwin16 cohorts (Study II N=1245 men, Study III N=724 men, Study IV N=2122 men, Study V N=2426 women and N=1962 men), who were assessed by a questionnaire at the age 22-28 y. In addition, 49 men and 526 women were assessed by a diagnostic interview. The overall response rates for both twin cohorts in all studies were 80-90%. In boys, mainly genetic factors (82%, 95% confidence interval [CI] 72-92) explained the covariation of self-esteem between the ages 14 y and 17 y, whereas in girls, environmental factors (69%, 95% CI 43-93) were the largest contributors. Of young men, 30% experienced high muscle dissatisfaction, while 12% used or had used muscle building supplements and/or anabolic steroids on a regular basis. Muscle dissatisfaction exhibited a robust association with the indicators of mental distress and a genetic component (42%, 95% CI 23-59) for its liability in this population was found. The variation of muscle-building substance use was primarily explained by the environmental factors. The incidence rate of anorexia nervosa in males for the age of 10-24 y was 15.7 (95% CI 6.6-37.8) per 100 000 person-years, and its lifetime prevalence by the young adulthood was 0.24% (95% CI 0.03-0.44). All detected probands with anorexia nervosa had recovered from eating disorders, but suffered from substantial psychiatric comorbidity, which manifested also in their co-twins. Additionally, male co-twins of the probands displayed significant dissatisfaction with body musculature, a male-specific feature of body dysmorphic disorder. All probands were from twin pairs discordant for eating disorders. Of the five male probands with anorexia nervosa, only one was from an opposite-sex twin pair. Among women from the opposite-sex pairs, the prevalence of DSM-IV or broad anorexia nervosa was no significantly different compared to that of the women from monozygotic pairs or from dizygotic same-sex pairs. The prevalence of DSM-IV or broad bulimia nervosa did not differ in opposite- versus same-sex female twin individuals either. In both sexes, the overall profile of indicators on eating disorders was rather similar between individuals from opposite-sex and same-sex pairs. In adolescence, development of self-esteem was differently regulated in boys compared to girls: this finding may have far-reaching implications on the etiology of sex discrepancy of internalizing and externalizing disorders. In young men, muscle dissatisfaction and muscle building supplement/steroid use were relatively common. Muscle dissatisfaction was associated with marked psychological distress such as symptoms of depression and disordered eating. Both genetic and environmental factors explained muscle dissatisfaction in the population, but environmental factors appeared to best explain the use of muscle-building substances. In this study, anorexia nervosa in boys and young men from the general population was more common, transient and accompanied by more substantial co-morbidity than previously thought. Co-twins of the probands with anorexia nervosa displayed significant psychopathology such as male specific symptoms of body dysmorphic disorder, but none of them had had an eating disorder: taken together, these traits are suggestive for an endophenotype of anorexia nervosa in males. Little evidence was found on that the risk for anorexia nervosa, bulimia nervosa, disordered eating or body dissatisfaction were associated with twin zygosity. Thus, it is unlikely that in utero femininization, masculinization or postnatal socialization according to the sex of the co-twin have a major influence on the later development of eating disorders or related traits.

Examination of Genetic Components Affecting Human Obesity-Related Quantitative Traits

Obesity increases the risk for several conditions, including type 2 diabetes mellitus, cardiovascular disease, hypertension, osteoarthirits and certain types of cancer. Twin- and family studies have shown that there is a major genetic component in the determination of body mass. In recent years several technological and scientific advance have been made in obesity research. For instance, novel replicated loci have been revealed by a number of genome wide association studies. This thesis aimed to investigate the association of genetic factors and obesity-related quantitative traits. The first study investigated the role of the lactase gene in anthropometric traits. We genetically defined lactose persistence by genotyping 31 720 individuals of European descent. We found that lactase persistence was significantly correlated with weight and body mass index but not with height. In the second study we performed the largest whole genome linkage scan for body mass index to date. The sample consisted of 4401 twin families and 10 535 individuals from six European countries. We found supporting evidence for two loci (3q29 and 7q36). We observed that the heritability estimate increased substantially when additional family members were removed from the analyses, which suggests reduced environmental variance in the twin sample. In the third study we assessed metabonomic, transcriptomic and genomic variation in a Finnish population cohort of 518 individuals. We formed gene expression networks to portray pathways and showed that a set of highly correlated genes of an inflammatory pathway associated with 80 serum metabolites (of 134 quantified measures). Strong association was found, for example, with several lipoprotein subclasses. We inferred causality by using genetic variation as anchors. The expression of the network genes was found to be dependent on the circulatory metabolite concentrations.

Influence of plant traits on production costs and profitability of strawberry in southeast Queensland.

In Queensland the subtropical strawberry ( Fragaria * ananassa) breeding program aims to combine traits into novel genotypes that increase production efficiency. The contribution of individual plant traits to cost and income under subtropical Queensland conditions was investigated, with the overall goal of improving the profitability of the industry through the release of new strawberry cultivars. The study involved specifying the production and marketing system using three cultivars of strawberry that are currently widely grown annually in southeast Queensland, developing methods to assess the economic impact of changes to the system, and identifying plant traits that influence outcomes from the system. From May through September P (price; $ punnet -1), V (monthly mass; tonne of fruit on the market) and M (calendar month; i.e. May=5) were found to be related ( r2=0.92) by the function (SE) P=4.741(0.469)-0.001630(0.0005) V-0.226(0.102) M using data from 2006 to 2010 for the Brisbane central market. Both income and cost elements in the gross margin were subject to sensitivity analysis. 'Harvesting' and 'Handling/Packing' 'Groups' of 'Activities' were the major contributors to variable costs (each >20%) in the gross margin analysis. Within the 'Harvesting Group', the 'Picking Activity' contributed most (>80%) with the trait 'display of fruit' having the greatest (33%) influence on the cost of the 'Picking Activity'. Within the 'Handling/Packing Group', the 'Packing Activity' contributed 50% of costs with the traits 'fruit shape', 'fruit size variation' and 'resistance to bruising' having the greatest (12-62%) influence on the cost of the 'Packing Activity'. Non-plant items (e.g. carton purchases) made up the other 50% of the costs within the 'Handling/Packing Group'. When any of the individual traits in the 'Harvesting' and 'Handling/Packing' groups were changed by one unit (on a 1-9 scale) the gross margin changed by up to 1%. Increasing yield increased the gross margin to a maximum (15% above present) at 1320 g plant -1 (94% above present). A 10% redistribution of total yield from September to May increased the gross margin by 23%. Increasing fruit size increased gross margin: a 75% increase in fruit size (to ~30 g) produced a 22% increase in the gross margin. The modified gross margin analysis developed in this study allowed simultaneous estimation of the gross margin for the producer and gross value of the industry. These parameters sometimes move in opposite directions.

QTL for nodal root angle in sorghum (Sorghum bicolor L. Moench) co-locate with QTL for traits associated with drought adaptation.

Nodal root angle in sorghum influences vertical and horizontal root distribution in the soil profile and is thus relevant to drought adaptation. In this study, we report for the first time on the mapping of four QTL for nodal root angle (qRA) in sorghum, in addition to three QTL for root dry weight, two for shoot dry weight, and three for plant leaf area. Phenotyping was done at the six leaf stage for a mapping population (n = 141) developed by crossing two inbred sorghum lines with contrasting root angle. Nodal root angle QTL explained 58.2% of the phenotypic variance and were validated across a range of diverse inbred lines. Three of the four nodal root angle QTL showed homology to previously identified root angle QTL in rice and maize, whereas all four QTL co-located with previously identified QTL for stay-green in sorghum. A putative association between nodal root angle QTL and grain yield was identified through single marker analysis on field testing data from a subset of the mapping population grown in hybrid combination with three different tester lines. Furthermore, a putative association between nodal root angle QTL and stay-green was identified using data sets from selected sorghum nested association mapping populations segregating for root angle. The identification of nodal root angle QTL presents new opportunities for improving drought adaptation mechanisms via molecular breeding to manipulate a trait for which selection has previously been very difficult.

Finding genes for economically important traits: Brahman cattle puberty.

Age at puberty is an important component of reproductive performance in beef cattle production systems. Brahman cattle are typically late-pubertal relative to Bos taurus cattle and so it is of economic relevance to select for early age at puberty. To assist selection and elucidate the genes underlying puberty, we performed a genome-wide association study (GWAS) using the BovineSNP50 chip (similar to 54 000 polymorphisms) in Brahman bulls (n = 1105) and heifers (n = 843) and where the heifers were previously analysed in a different study. In a new attempt to generate unbiased estimates of single-nucleotide polymorphism (SNP) effects and proportion of variance explained by each SNP, the available data were halved on the basis of year and month of birth into a calibration and validation set. The traits that defined age at puberty were, in heifers, the age at which the first corpus luteum was detected (AGECL, h(2) = 0.56 +/- 0.11) and in bulls, the age at a scrotal circumference of 26 cm (AGE26, h(2) = 0.78 +/- 0.10). At puberty, heifers were on average older (751 +/- 142 days) than bulls (555 +/- 101 days), but AGECL and AGE26 were genetically correlated (r = 0.20 +/- 0.10). There were 134 SNPs associated with AGECL and 146 SNPs associated with AGE26 (P < 0.0001). From these SNPs, 32 (similar to 22%) were associated (P < 0.0001) with both traits. These top 32 SNPs were all located on Chromosome BTA 14, between 21.95 Mb and 28.4 Mb. These results suggest that the genes located in that region of BTA 14 play a role in pubertal development in Brahman cattle. There are many annotated genes underlying this region of BTA 14 and these are the subject of current research. Further, we identified a region on Chromosome X where markers were associated (P < 1.00E-8) with AGE26, but not with AGECL. Information about specific genes and markers add value to our understanding of puberty and potentially contribute to genomic selection. Therefore, identifying these genes contributing to genetic variation in AGECL and AGE26 can assist with the selection for early onset of puberty.

Genome-wide association studies of quantitative traits with related individuals: Little (power) lost but much to be gained

For complex disease genetics research in human populations, remarkable progress has been made in recent times with the publication of a number of genome-wide association scans (GWAS) and subsequent statistical replications. These studies have identified new genes and pathways implicated in disease, many of which were not known before. Given these early successes, more GWAS are being conducted and planned, both for disease and quantitative phenotypes. Many researchers and clinicians have DNA samples available on collections of families, including both cases and controls. Twin registries around the world have facilitated the collection of large numbers of families, with DNA and multiple quantitative phenotypes collected on twin pairs and their relatives. In the design of a new GWAS with a fixed budget for the number of chips, the question arises whether to include or exclude related individuals. It is commonly believed to be preferable to use unrelated individuals in the first stage of a GWAS because relatives are 'over-matched' for genotypes. In this study, we quantify that for GWAS of a quantitative phenotype, relative to a sample of unrelated individuals surprisingly little power is lost when using relatives. The advantages of using relatives are manifold, including the ability to perform more quality control, the choice to perform within-family tests of association that are robust to population stratification, and the ability to perform joint linkage and association analysis. Therefore, the advantages of using relatives in GWAS for quantitative traits may well outweigh the small disadvantage in terms of statistical power.

Male traits and herd reproductive capability in tropical beef cattle. 1. Experimental design and animal measures

Research into the genetics of whole herd profitability has been a focus of the Beef Cooperative Research Centre for Beef Genetic Technologies over the past decade and it has been identified that measures of male reproduction may offer a potential indirect means of selecting for improved female reproduction. This paper describes the experimental design and provides a descriptive analysis of an array of male traits in Brahman and Tropical Composite genotypes managed under the medium to high stress, semi-extensive to extensive production systems of northern Australia. A total of 1639 Brahman and 2424 Tropical Composite bulls with known pedigrees, bred and raised in northern Australia, were evaluated for a comprehensive range of productive and reproductive traits. These included blood hormonal traits (luteinising hormone, inhibin and insulin-like growth factor-I); growth and carcass traits (liveweight, body condition score, ultrasound scanned 12-13th rib fat, rump P8 fat, eye muscle area and hip height); adaptation traits (flight time and rectal temperature); and a bull breeding soundness evaluation (leg and hoof conformation, sheath score, length of everted prepuce, penile anatomy, scrotal circumference, semen mass activity, sperm motility and sperm morphology). Large phenotypic variation was evident for most traits, with complete overlap between genotypes, indicating that there is likely to be a significant opportunity to improve bull fertility traits through management and bull selection.

Male traits and herd reproductive capability in tropical beef cattle. 2. Genetic parameters of bull traits

A total of 4063 young bulls of two tropical genotypes (1639 Brahman and 2424 Tropical Composite) raised in northern Australia were evaluated for a comprehensive range of production and reproduction traits up to 24 months of age. Prior to weaning, peripheral blood concentrations of luteinising hormone (LH) and inhibin were measured at 4 months of age. At weaning (6 months) blood insulin-like growth factor-1 (IGF-I) and flight time were recorded. Body composition traits of fat depth and eye-muscle area were determined by ultrasonography at 15 months of age when additional measurements of liveweight, hip height and body condition score were recorded. Bull breeding soundness was evaluated at similar to 12, 18 and 24 months of age when measurements of scrotal circumference, sheath score, semen mass activity, progressive motility of individual sperm and percent morphologically normal sperm were recorded. Magnitude of heritability and genetic correlations changed across time for some traits. Heritability of LH, inhibin, IGF-I and of 18-month scrotal circumference, mass activity, progressive motility and percent normal sperm was 0.31, 0.74, 0.44, 0.75, 0.24, 0.15 and 0.25, respectively, for Brahmans and 0.48, 0.72, 0.36, 0.43, 0.13, 0.15 and 0.20, respectively, for Tropical Composites. Inhibin and IGF-I had moderate genetic association with percent normal sperm at 24 months in Brahmans but low to negligible associations in Tropical Composites. Body condition score in Brahmans and sperm motility (mass and individual) traits in both genotypes had moderate to strong genetic correlation with percent normal sperm and may prove useful candidates for indirect selection. There is scope to increase scrotal circumference by selection and this will be associated with favourable correlated responses of improved semen quality in both genotypes. The lack of genetic antagonism among bull traits indicates that selection for improved semen quality will not adversely affect other production traits.

Predicting Additive and Non-additive Genetic Effects from Trials Where Traits Are Affected by Interplot Competition

There are two key types of selection in a plant breeding program, namely selection of hybrids for potential commercial use and the selection of parents for use in future breeding. Oakey et al. (in Theoretical and Applied Genetics 113, 809-819, 2006) showed how both of these aims could be achieved using pedigree information in a mixed model analysis in order to partition genetic effects into additive and non-additive effects. Their approach was developed for field trial data subject to spatial variation. In this paper we extend the approach for data from trials subject to interplot competition. We show how the approach may be used to obtain predictions of pure stand additive and non-additive effects. We develop the methodology in the context of a single field trial using an example from an Australian sorghum breeding program.

Biochemical and structural properties of Potato virus A VPg

The potato virus A (PVA) genome linked protein (VPg) is a multifunctional protein that takes part in vital infection cycle events such as replication and movement of the virus from cell to cell. VPg is attached to the 5´ end of the genome and is carried in the tip structure of the filamentous virus particle. VPg is also the last protein to be cleaved from the polyprotein. VPg interacts with several viral and host proteins and is phosphorylated at several positions. These features indicate a central role in virus epidemiology and a requirement for an efficient but flexible mechanism for switching between different functions. -- This study examines some of the key VPg functions in more detail. Mutations in the positively charged region from Ala38 to Lys44 affected the NTP binding, uridylylation, and in vitro translation inhibition activities of VPg, whereas in vivo translation inhibition was not affected. Some of the data generated in this study implicated the structural flexibility of the protein in functional activities. VPg lacks a rigid structure, which could allow it to adapt conformationally to different functions as needed. A major finding of this study is that PVA VPg belongs to the class of ´intrinsically disordered proteins´ (IDPs). IDPs are a novel protein class that has helped to explain the observed lack of structure. The existence of IDPs clearly shows that proteins can be functional and adapt a native fold without a rigid structure. Evidence for the intrinsic disorder of VPg was provided by CD spectroscopy, NMR, fluorescence spectroscopy, bioinformatic analysis, and limited proteolytic digestion. The structure of VPg resembles that of a molten globule-type protein and has a hydrophobic core domain. Approximately 50% of the protein is disordered and an α-helical stabilization of these regions has been hypothesized. Surprisingly, VPg structure was stabilized in the presence of anionic lipid vesicles. The stabilization was accompanied by a change in VPg structure and major morphological modifications of the vesicles, including a pronounced increase in the size and appearance of pore or plaque like formations on the vesicle surface. The most likely scenario seems to be an α-helical stabilization of VPg which induces formation of a pore or channel-like structure on the vesicle surface. The size increase is probably due to fusion or swelling of the vesicles. The latter hypothesis is supported by the evident disruption of the vesicles after prolonged incubation with VPg. A model describing the results is presented and discussed in relation to other known properties of the protein.

Specificity of protein - Nucleic acid interaction and the biochemical evolution

The water soluble carbodiimide mediated condensation of dipeptides of the general form Gly-X was carried out in the presence of mono- and poly-nucleotides. The observed yield of the tetrapeptide was found to be higher for peptide-nucleotide system of higher interaction specificity following mainly the anticodon-amino acid relationship (Basu, H.S. & Podder, S.K., 1981, Ind. J. Biochem. Biophys.,19, 251-253). The yield of the condensation product of L-peptide was more because of its higher interaction specificity. The extent of the racemization during the condensation of Gly-L-Phe, Gly-L-Tyr and Gly-D-Phe was found to be dependent on the specificity of the interaction -the higher the specificity, the lesser the racemization. The product formed was shown to have a catalytic effect on the condensation reaction. These data thus provide a mechanism showing how the specific interaction between amino acids/dipeptides and nucleic acids could lead to the formation of the lsquoprimitiversquo translation machinery.

The use of genetic correlations to evaluate associations between SNP markers and quantitative traits

Open-pollinated progeny of Corymbia citriodora established in replicated field trials were assessed for stem diameter, wood density, and pulp yield prior to genotyping single nucleotide polymorphisms (SNP) and testing the significance of associations between markers and assessment traits. Multiple individuals within each family were genotyped and phenotyped, which facilitated a comparison of standard association testing methods and an alternative method developed to relate markers to additive genetic effects. Narrow-sense heritability estimates indicated there was significant additive genetic variance within this population for assessment traits ( h ˆ 2 =0.28to0.44 ) and genetic correlations between the three traits were negligible to moderate (r G = 0.08 to 0.50). The significance of association tests (p values) were compared for four different analyses based on two different approaches: (1) two software packages were used to fit standard univariate mixed models that include SNP-fixed effects, (2) bivariate and multivariate mixed models including each SNP as an additional selection trait were used. Within either the univariate or multivariate approach, correlations between the tests of significance approached +1; however, correspondence between the two approaches was less strong, although between-approach correlations remained significantly positive. Similar SNP markers would be selected using multivariate analyses and standard marker-trait association methods, where the former facilitates integration into the existing genetic analysis systems of applied breeding programs and may be used with either single markers or indices of markers created with genomic selection processes.

Career adaptability predicts subjective career success above and beyond personality traits and core self-evaluations

The Career Adapt-Abilities Scale (CAAS) measures career adaptability as a higher-order construct that integrates four psychosocial resources of employees for managing their career development: concern, control, curiosity, and confidence. The goal of the present study was to investigate the validity of the CAAS with regard to its effects on two indicators of subjective career success (career satisfaction and self-rated career performance) above and beyond the effects of employees' Big Five personality traits and core self-evaluations. Data came from a large and heterogeneous sample of employees in Australia (N=1723). Results showed that overall career adaptability positively predicted career satisfaction and self-rated career performance above and beyond the Big Five personality traits and core self-evaluations. In addition, concern and confidence positively predicted the two indicators of subjective career success. The findings provide further support for the incremental validity of the CAAS.

QTL associated with barley (Hordeum vulgare) feed quality traits measured through in situ digestion

Barley (Hordeum vulgare) is a major feed source for the intensive livestock industry. Competitiveness against other cereal grains depends largely on the price per unit of expressed feed quality. The traits which contribute to feed quality in barley are largely quantitative in nature but little is known about their genetic control. A study to identify the quantitative trait loci (QTLs) associated with feed quality was performed using a F6-derived recombinant inbred barley population. Samples from each line were incubated in the rumen of fistulated cattle, recovered, washed and dried for determination of in situ dry matter digestibility. Additionally, both pre- and post-digestion samples were analysed to quantify the content of key quality components relating to acid detergent fibre, total starch and protein. The data was used to identify trait-associated QTLs. Genetic analysis identified significant QTLs on chromosomes 2H, 5H and 7H. Genetic markers linked to these QTL should provide an effective tool for the selection and improvement of feed barley in the future.