Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4 (62.3 (55.1�70.8) million) to 6.4 (58.3 (47.6�70.7) million), but is predicted to remain above the World Health Organization�s Global Nutrition Target of <5 in over half of LMICs by 2025. Prevalence of overweight increased from 5.2 (30 (22.8�38.5) million) in 2000 to 6.0 (55.5 (44.8�67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic. © 2020, The Author(s)

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

Progress in larviculture of the Atlantic halibut <i>Hippoglossus hippoglossus</i>

The main goal of the project is to develop intensive industrial scale production systems for halibut fry. Halibut eggs were obtained from three brood stocks both by stripping and by natural spawning. Photoperiod manipulation is used to increase the spawning period, and spawning now takes place in the period February to June/July. The eggs are disinfected and incubated in up-stream conical tanks (8°C, darkness) and transferred to larval incubators after hatching. Two incubator-types are used; small glass bowls (3 liter), run stagnant or semi-stagnant, or large conical silos (0.7-15m³) run with continuous water flow (4-8°C, darkness). These different systems can be used to bring the yolk sac larvae of halibut up to the stage of first feeding. The yolk sac phase lasts for 35-50 days dependent of the temperature, and the larvae are very sensitive to physical conditions (light, temperature, water currents) and the environmental microbial community during this development stage. The survival averages 80% (for adequate groups) in small bowls and 50-70% in large flow-through silo incubators.Adjustment of the light conditions is presently among the main challenges in halibut first feeding. The larvae are positively attracted by all light qualities and dense schooling in the surface of the tank is a frequent observation. Such behaviour will result in extensive mortality in a matter of a week, and must in all events be avoided. Use of submerged light or strong sublight, which has been reduced to 30% intensity by appropriate filters, combined with algal addition to the fish tanks have yielded adequate behavioural response and in turn positive feeding results, but the mechanisms are not adequately understood so far.The rotifer Brachionus plicatilis and Artemia enriched by long chain omega3 fatty acids by use of emulsified lipid diets (Selco-type, Artemia Systems SA, Belgium) have been used as live feed for the halibut larvae. The rotifers are normally used during the first 10-15 days, but attempts have been made to use small Artemia instead of the rotifer. Larger on-grown Artemia has been used after 3-4 weeks of feeding. Addition of microalgae to the fish tanks enhance both growth rate and survival through the phase of the first feeding. The larvae increase their body weight by approximately 10% per day in the initial phase (13°C), provided that adequate diets are used. Weaning may be started beyond day 50 after the start of first feeding, and metamorphosis will occur at the same time. Survival up to 20% has been obtained so far