Genome-wide association study identifies common and low-frequency variants at the AMHgene locus that strongly predict serum AMH levels in males

Anti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the foetus and is an emerging biomarker of postnatal reproductive function in females. Due to a paucity of adequately sized studies, the genetic determinants of circulating AMH levels are poorly characterized. In samples from 2815 adolescents aged 15 from the ALSPAC study, we performed the first genome-wide association study of serum AMH levels across a set of ∼9 M ‘1000 Genomes Reference Panel’ imputed genetic variants. Genetic variants at the AMH protein-coding gene showed considerable allelic heterogeneity, with both common variants [rs4807216 (PMale = 2 × 10−49, Beta: ∼0.9 SDs per allele), rs8112524 (PMale = 3 × 10−8, Beta: ∼0.25)] and low-frequency variants [rs2385821 (PMale = 6 × 10−31, Beta: ∼1.2, frequency 3.6%)] independently associated with apparently large effect sizes in males, but not females. For all three SNPs, we highlight mechanistic links to AMH gene function and demonstrate highly significant sex interactions (PHet 0.0003–6.3 × 10−12), culminating in contrasting estimates of trait variance explained (24.5% in males versus 0.8% in females). Using these SNPs as a genetic proxy for AMH levels, we found no evidence in additional datasets to support a biological role for AMH in complex traits and diseases in men

A study of protein and amino nutrition of growing pigs.

End of Project ReportProtein nutrition of the pig is concerned primarily with supplying the amino acid requirements for fast, efficient growth and development of a lean carcass. In addition, surplus protein contributes to a high level of nitrogen excretion in manure which is a problem in complying with the Nitrates Directive. Metabolism of the excess protein / nitrogen in the pig involves creation of urea and this process depresses the efficiency of energy utilisation. As the pig grows, its requirement for individual amino acids falls but the optimum ratio changes. Providing a diet with the correct levels and balance of the principal amino acids is expected to improve performance. Improvements in genetics and changes in management such as slaughter weight require that the amino acid requirements be reassessed periodically. The objective of this study was to examine response of pigs to variation in dietary lysine in several weight ranges with the concentrations of the other principal amino acids held constant. Entire males had superior FCR to females in all trials except 15 to 30kg, but differences in dietary lysine requirements did not occur until the finishing stage. At heavier weights, response of male and female pigs began to diverge at lysine concentrations greater than 10.7 g/kg (ADG) and 9.7 g/kg (FCR). There appeared to be a need to increase the threonine to lysine ratio in the diet from 0.60 to 0.70 when lysine concentration was reduced from 12.0 to 9.5 g/kg as weight of the pig increased. Providing the same mean lysine content (11.1 g/kg) to pigs from 38 to 97 kg in a series of five diets declining in lysine concentration compared with a single diet did not affect performance, or reduce N excretion. However, lowering the overall mean lysine concentration from 11g/kg to 10.0 g/kg reduced overall N excretion by 13 %, without a negative effect on pig performance. Pigs which were offered a low lysine diet in the early stage of growth exhibited a compensatory response during realimentation on a high lysine diet but it was not sufficient to equal the overall performance of pigs previously offered a lysine-adequate diet. Nitrogen excretion was reduced by 23 % while the low lysine diet was fed in the initial period but there was no residual effect on N excretion during realimentation.Teagasc Walsh Fellowship ProgrammeNational Development Programme Funds (NDP

Effect of water-to-feed ratio on feed disappearance, growth rate, feed efficiency, and carcass traits in growing-finishing pigs

peer-reviewedThe optimum proportion of water for preparing liquid feed to maximize growth and optimize feed efficiency (FE) in growing-finishing pigs is not known. The aim of the current study was, using an automatic short-trough sensor liquid feeding system, to identify the water-to-feed ratio at which growth was maximized and feed was most efficiently converted to live-weight. Two experiments were conducted in which four commercially used water-to-feed ratios were fed: 2.4:1, 3.0:1, 3.5:1, and 4.1:1 on a dry matter (DM) basis (the equivalent of 2:1, 2.5:1, 3.0:1, and 3.5:1 on a fresh matter basis). Each experiment comprised 216 pigs, penned in groups of 6 same sex (entire male and female) pigs/pen with a total of 9 pen replicates per treatment. The first experiment lasted 62 days (from 40.6 to 102.2 kg at slaughter) and the second experiment was for 76 days (from 31.8 to 119.6 kg at slaughter). Overall, in Exp. 1, FE was 0.421, 0.420, 0.453, and 0.448 (s.e. 0.0081 g/g; P < 0.01) for pigs fed at 2.4:1, 3.0:1, 3.5:1, and 4.1:1, respectively. Overall, in Exp. 2, average daily gain was 1,233, 1,206, 1,211, and 1,177 (s.e. 12.7 g/day; P < 0.05) for pigs fed at 2.4:1, 3.0:1, 3.5:1, and 4.1:1, respectively. At slaughter, in Exp. 1, dressing percentage was 76.7, 76.6, 76.7, and 75.8 (s.e. 0.17%; P < 0.01) for 2.4:1, 3.0:1, 3.5:1, and 4.1:1, respectively. There were no differences between treatment groups for DM, organic matter, nitrogen, gross energy, or ash digestibilities. These findings indicate that liquid feeding a diet prepared at a water-to-feed ratio of 3.5:1 maximizes FE of growing-finishing pigs without negatively affecting dressing percentage. Therefore, preparing liquid feed for growing-finishing pigs at a water-to-feed ratio of 3.5:1 DM is our recommendation for a short-trough liquid feeding system

Effect of Raw and Extruded Propionic Acid-Treated Field Beans on Energy and Crude Protein Digestibility (In-Vitro and In-Vivo), Growth and Carcass Quality in Grow-Finisher Pigs

The in-vitro ileal digestibility of dry matter (DM), organic matter (OM), and crude protein (CP) of field beans treated with propionic acid (trFB) and extruded trFB (exFB) was determined in experiment 1. The DE and dCP values of trFB and exFB were determined using the difference method in experiment 2. The effect of replacing SBM with trFB and exFB in grow-finisher diets on growth, carcass quality, apparent ileal digestibility (AiD), and total tract digestibility (ATTD) of DM, OM, gross energy (GE), and CP were investigated in experiment 3. In exp. 1, in-vitro digestibility of exFB compared to trFB was unchanged for DM (p = 0.12), increased for OM (p 0.05).info:eu-repo/semantics/publishedVersio

The Avon Longitudinal Study of Parents and Children:Generation 2 questionnaire data capture May-July 2020 [version 2; peer review: 3 approved]

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 from the Bristol area (UK). ALSPAC has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. From 2012, ALSPAC has identified G1 participants who were pregnant (or their partner was) or had become parents, and enrolled them, their partners, and children in the ALSPAC-Generation 2 (ALSPAC-G2) study, providing a unique multigenerational cohort. At present, approximately 1,100 G2 children (excluding those in utero) from 810 G1 participants have been enrolled. In response to the COVID-19 pandemic, ALSPAC rapidly deployed two online questionnaires; one during the initial lockdown phase in 2020 (9th April-15th May), and another when national lockdown restrictions were eased (26th May-5th July). As part of this second questionnaire, G1 parents completed a questionnaire about each of their G2 children. This covered: parental reports of children’s feelings and behaviour since lockdown, school attendance, contact patterns, and health. A total of 289 G1 participants completed this questionnaire on behalf of 411 G2 children. This COVID-19 G2 questionnaire data can be combined with prepandemic ALSPAC-G2 data, plus ALSPAC-G1 and -G0 data, to understand how children’s health and behaviour has been affected by the pandemic and its management. Data from this questionnaire will be complemented with linkage to health records and results of biological testing as they become available. Prospective studies are necessary to understand the impact of this pandemic on children’s health and development, yet few relevant studies exist; this resource will aid these efforts. Data has been released as: 1) a freely-available dataset containing participant responses with key sociodemographic variables; and 2) an ALSPAC-held dataset which can be combined with existing ALSPAC data, enabling bespoke research across all areas supported by the study

Physical activity as a treatment for depression: the TREAD randomised trial protocol

Published version. Copyright © 2010 BioMed CentralBackground: Depression is one of the most common reasons for consulting a General Practitioner (GP) within the UK. Whilst antidepressants have been shown to be clinically effective, many patients and healthcare professionals would like to access other forms of treatment as an alternative or adjunct to drug therapy for depression. A recent systematic review presented some evidence that physical activity could offer one such option, although further investigation is needed to test its effectiveness within the context of the National Health Service. The aim of this paper is to describe the protocol for a randomised, controlled trial (RCT) designed to evaluate an intervention developed to increase physical activity as a treatment for depression within primary care. Methods/design: The TREAD study is a pragmatic, multi-centre, two-arm RCT which targets patients presenting with a new episode of depression. Patients were approached if they were aged 18-69, had recently consulted their GP for depression and, where appropriate, had been taking antidepressants for less than one month. Only those patients with a confirmed diagnosis of a depressive episode as assessed by the Clinical Interview Schedule-Revised (CIS-R), a Beck Depression Inventory (BDI) score of at least 14 and informed written consent were included in the study. Eligible patients were individually randomised to one of two treatment groups; usual GP care or usual GP care plus facilitated physical activity. The primary outcome of the trial is clinical symptoms of depression assessed using the BDI four months after randomisation. A number of secondary outcomes are also measured at the 4-, 8- and 12-month follow-up points including quality of life, attitude to and involvement in physical activity and antidepressant use/adherence. Outcomes will be analysed on an intention-to-treat (ITT) basis and will use linear and logistic regression models to compare treatments. Discussion: The results of the trial will provide information about the effectiveness of physical activity as a treatment for depression. Given the current prevalence of depression and its associated economic burden, it is hoped that TREAD will provide a timely contribution to the evidence on treatment options for patients, clinicians and policy-makers

Is Height2.7 Appropriate for Indexation of Left Ventricular Mass in Healthy Adolescents?:The Importance of Sex Differences

BACKGROUND:Left ventricular mass (LVM) is an important predictor of cardiovascular risk. In adolescence, LVM is commonly indexed to height2.7, although some evidence suggests that this may not fully account for sex differences.METHODS:We investigated appropriate allometric scaling of LVM to height, total lean mass, and body surface area, in a UK birth cohort of 2039 healthy adolescents (17±1 years). Allometric relationships were determined by linear regression stratified by sex, following log transformation of x and y variables [log(y)=a+b×log(x)], b is the allometric exponent.RESULTS:Log (LVM) showed linear relationships with log(height) and log(lean mass). Biased estimates of slope resulted when the sexes were pooled. The exponents were lower than the conventional estimate of 2.7 for males (mean [95% CI]=1.66 [1.30–2.03]) and females (1.58 [1.27–1.90]). When LVM was indexed to lean mass, the exponent was 1.16 (1.05–1.26) for males and 1.07 (0.97–1.16) for females. When LVM was indexed to estimated body surface area, the exponent was 1.53 (1.40–1.66) for males and 1.34 (1.24–1.45) for females.CONCLUSIONS:Allometric exponents derived from pooled data, including men and women without adjustment for sex were biased, possibly due to sex differences in body composition. We suggest that when assessing LVM, clinicians should consider body size, body composition, sex, and age. Our observations may also have implications for the identification of young individuals with cardiac hypertrophy