A genome-wide association study of early menopause and the combined impact of identified variants

Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smokin

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

The Influence of Rotational Length, along with Pre- and Post-Grazing Measures on Nutritional Composition of Pasture during Winter and Spring on New Zealand Dairy Farms

The quality of ryegrass&ndash;clover pasture was investigated between August (winter: start of calving) and November (spring: end of breeding) on pasture-based dairy farms (&gt;85% of total feed from pasture) that had short (n = 2, Farms A and B; winter ~30 days, spring ~20&ndash;25 days) or long (n = 2, Farms C and D; winter ~35 days, spring ~25&ndash;30 days) grazing rotations to determine whether quality was affected by grazing rotation length (RT). Weekly assessments of pasture growth and herbage quality were made using a standardised electronic rising plate meter, and near-infrared spectroscopy, respectively. Data were subjected to repeated measure mixed model analysis, in which herbage quality was the outcome variable. The highest pre-grazing dry matter (PGDM) and height, post-grazing dry matter (DM) and height, and number of live leaves per tiller (leaf regrowth stage, LS) were present in late spring. Neutral detergent fibre (NDF), acid detergent fibre (ADF), metabolisable energy (ME), and organic matter digestibility (OMD) were positively correlated to each other (r2 &ge; 0.8) whilst ADF and lipid, and ADF and OMD were negatively correlated (r2 &ge; &minus;0.8; p &lt; 0.01). Metabolisable energy content was negatively correlated with ADF and NDF (r2 = &minus;0.7, &minus;0.8, respectively), and was inversely related to PGDM. Metabolisable energy was higher (p &lt; 0.05) in farms with shorter (overall mean: 11.2 MJ/kg DM) than longer (10.9 MJ/kg DM) RT. Crude protein was also inversely related to PGDM and was higher with shorter (23.2% DM) than longer (18.3% DM; p &lt; 0.05) RT. Pre-grazing DM affected the amount of pasture that was grazed and, hence, the amount of DM remaining after grazing (post-grazing DM or residual), so that PGDM was correlated with post-grazing height and residual DM (r2 = 0.88 and 0.51, respectively; both p &lt; 0.001). In conclusion, RT, LS, and PGDM during winter and spring influenced the herbage quality, therefore, better management of pastures may enhance the productivity of dairy cows

From Partnerships to Networks: New Approaches for Measuring U.S. National Heritage Area Effectiveness

National Heritage Areas (NHAs) are an alternative and increasingly popular form of protected area management in the United States. NHAs seek to integrate environmental objectives with community and economic objectives at regional or landscape scales. NHA designations have increased rapidly in the last 20 years, generating a substantial need for evaluative information about (a) how NHAs work; (b) outcomes associated with the NHA process; and (c) the costs and benefits of investing public moneys into the NHA approach. Qualitative evaluation studies recently conducted at three NHAs have identified the importance of understanding network structure and function in the context of evaluating NHA management effectiveness. This article extends these case studies by examining quantitative network data from each of the sites. The authors analyze these data using both a descriptive approach and a statistically more robust approach known as exponential random graph modeling. Study findings indicate the presence of transitive structures and the absence of three-cycle structures in each of these networks. This suggests that these networks are relatively ‘‘open,’’ which may be desirable, given the uncertainty of the environments in which they operate. These findings also suggest, at least at the sites reported here, that the NHA approach may be an effective way to activate and develop networks of intersectoral organizational partners. Finally, this study demonstrates the utility of using quantitative network analysis to better understand the effectiveness of protected area management models that rely on partnership networks to achieve their intended outcomes.national heritage areas; protected area management; landscape-scale conservation; evaluation; social network analysis

A Nutritional Investigation of Major Feed Types and Feed Rations Used in Medium-Scale Dairy Production Systems in Sri Lanka

In this paper, the nutritional quality, digestibility, and chemical composition of major feed types as well as the use of those feeds in rations by medium-scale dairy farmers in the Kurunegala district of Sri Lanka were studied. Nine dairy farms were visited fortnightly over a five-month period to identify the feeds that were commonly used. All farms operated under a stall-feeding system in which a manually mixed ration (MMR) was fed 2&ndash;3 times daily. Four forages were identified: Guinea grass ecotype A (Panicum maximum), called Guinea grass; Hybrid Napier CO-3 (Pennisetum purpureum &times; Pennisetum americanum), called CO-3 grass; Gliricidia (Gliricidia sepium); and maize stover (Zea mays L.), along with three other supplementary feeds (maize silage, barley distillers&rsquo; by-products, and commercially formulated cattle feed). These feeds were subjected to proximate analysis and in vitro digestibility analysis. The metabolisable energy (ME) of the forages ranged from 7.5&ndash;10.0 MJ/kg dry matter (DM), with the ME of Guinea grass and CO-3 grass (7.5 and 8.0 MJ/kg DM, respectively) being lower than that of Gliricidia (10.0 MJ/kg DM). The neutral detergent fibre (NDF) concentration of both Guinea grass and CO-3 grass (both 72% DM) was much higher than that of Gliricidia (47% DM). Crude protein (CP) was higher in Gliricidia (17.5% DM) than in either Guinea grass or CO-3 grass (8.0 and 8.8% DM, respectively). The ME of the supplementary feeds varied between 11.0 and 12.8 MJ/kg DM, while CP varied between 15.0 and 24.0% DM. The daily ME intake of cows was consistently 10% lower than their calculated daily energy requirement; for dry cows, the mean intake was 90 MJ/cow/day supplied vs. 101 MJ required, while for cows in early lactation the mean intake was 126 MJ/cow/day supplied vs. 140 MJ required. The average CP intake of lactating cows (13.5% DM) was inadequate (requirements: 16 to 17.5% DM), while the average CP intake of dry cows (11.8% DM) was satisfactory (requirements: 11 to 12% DM). The current study shows that the majority of the feed types used in these medium-scale dairy farms provide insufficient ME or CP to meet the nutritional requirements of either lactating or dry cows irrespective of the quantity of feed provided