Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Sequence variants in three loci influence monocyte counts and erythrocyte volume

Blood cells participate in vital physiological processes, and their numbers are tightly regulated so that homeostasis is maintained. Disruption of key regulatory mechanisms underlies many blood-related Mendelian diseases but also contributes to more common disorders, including atherosclerosis. We searched for quantitative trait loci (QTL) for hematology traits through a whole-genome association study, because these could provide new insights into both hemopoeitic and disease mechanisms. We tested 1.8 million variants for association with 13 hematology traits measured in 6015 individuals from the Australian and Dutch populations. These traits included hemoglobin composition, platelet counts, and red blood cell and white blood cell indices. We identified three regions of strong association that, to our knowledge, have not been previously reported in the literature. The first was located in an intergenic region of chromosome 9q31 near LPAR1, explaining 1.5% of the variation in monocyte counts (best SNP rs7023923, p=8.9x10(-14)). The second locus was located on chromosome 6p21 and associated with mean cell erythrocyte volume (rs12661667, p=1.2x10(-9), 0.7% variance explained) in a region that spanned five genes, including CCND3, a member of the D-cyclin gene family that is involved in hematopoietic stem cell expansion. The third region was also associated with erythrocyte volume and was located in an intergenic region on chromosome 6q24 (rs592423, p=5.3x10(-9), 0.6% variance explained). All three loci replicated in an independent panel of 1543 individuals (p values=0.001, 9.9x10(-5), and 7x10(-5), respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate.

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.

Organic diet development for black tiger prawns

The survival and growth of black tiger prawn (Penaeus monodon) juveniles (~3.3 g) were compared after feeding in tanks over one month with several prepared diets based on organically certified ingredients. The extrusion process in the manufacture of pelletised experimental diets was similar to processes used in commercial plants and was closely documented. The daily feeding rate (6% of starting mean body weight) was split equally into two feeds, one in the morning and one in the afternoon. All diets tested produced high survival (97-100%). A widely-used commercial Australian prawn feed was used as a control diet. It contained 41.2% protein with 29.5 g kg-1 lysine, and produced the highest (P<0.05) growth (117% weight gain). Three of the experimental organic diets tested (namely, 1. wheat + soy, 2. pig weaner diet + soy, and 3. pig weaner diet + dried fish waste) produced moderate growth (73–77% weight gain). These contained 33%, 36% or 31% protein, respectively, and produced better (P<0.05) growth than diets utilising a range of other prospective ingredients (eg: wheat + dried scallop gut, wheat + fish waste, wheat + chickpea, or wheat + macadamia meal, containing 23%, 25%, 29% or 24% protein, respectively). An unfed control-treatment produced the lowest (P<0.05) growth (4% weight gain). The water stability of the experimental diets that produced the best growth was poorer than the commercial diet, suggesting that improvements in this aspect of these organic feed’s manufacture could result in additional performance benefits and possibly reduced feed wastage. Analyses revealed a linear relationship between diet performance (in terms of weight gains) and the protein and lysine contents of diets. About 70% of diet performance was explained by these factors. The superior performance of the commercial diet could be attributed primarily to its formulation using mainly marine proteins, as well as a range of other unknown factors (commercial in confidence). These other factors range from use of feed attractants, better knowledge of ingredient nutrient availability, different extrusion conditions and the use of other unspecified micro-nutrients not present in the experimental diets. The organic diets studied still require a degree of fine-tuning before structured commercial uptake. This would sensibly include further detailed investigations of the composition and nutrient availabilities of these and other organic dietary ingredients, and refinement of the extrusion process for formulated diets.

A novel breeding programme for improved growth in barramundi Lates calcarifer (Bloch) using foundation stock from progeny-tested parents

Rapid genetic gains for growth in barramundi ( Lates calcarifer) appear achievable by starting a breeding programme using foundation stock from progeny tested broodstock. The potential gains of this novel breeding design were investigated using biologically feasible scenarios tested with computer simulation models. The design involves the production of a large number of full-sib families using artificial mating which are compared in common growout conditions. The estimated breeding values of their paternal parents are calculated using a binomial probit analysis to assess their suitability as foundation broodstock. The programme can theoretically yield faster rates of genetic gain compared to other breeding programmes for aquaculture species. Assuming a heritability of 0.25 for growth, foundation broodstock evaluated in two years had breeding values for faster growth ranging from 21% to 51% depending on the genetic diversity of stock under evaluation. As a comparison it will take between nine and twenty-two years to identify broodstock with similar breeding values in a contemporary barramundi breeding programme.

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.

Growing organic prawns - in inland saline waters

This report details the results of research into organic production of prawns in Australia. This has involved activities and experiments over two years at several sites and using a multidisciplinary approach. This includes farm trials at an inland demonstration prawn farm which solely utilises saline bore water, sample collection from two commercial prawn farms in coastal regions of south-eastern Queensland, replicated feed trials at one of DPI&F’s aquaculture research stations, specified feed manufacture at the laboratories of University of Queensland, and packaging and product storage trials and food analyses at two of DPI&F’s food technology laboratories. This work was designed to investigate and assist in the possible adoption of organic procedures by the Australian prawn farming industry. The import from Asia of cheaply produced prawns has forced all Australian prawn farmers to review their marketing procedures. Additionally investors are becoming increasingly concerned at the prospects for the expansion of this industry in Australia. Since the competition of seafood products in the marketplace is increasing on a global basis, alternate products are being investigated by those wishing to maintain and/or grow their market share. The premium paid for organic food products would hopefully provide an economic incentive for farmers to convert to organic production systems, with an added advantage that the standards that apply have beneficial implications also for the social and environmental practices of industry.