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Background Alcohol and nicotine codependence can be considered as a more severe subtype of alcohol dependence. A portion of its risk may be attributable to genetic factors. Methods We searched for significant risk genomic regions specific for this disorder using a genome-wide association study. A total of 8,847 subjects underwent gene-disease association analysis, including (i) a discovery cohort of 818 European American cases with alcohol and nicotine codependence and 1,396 European American controls, (ii) a replication cohort of 5,704 Australian family subjects with 907 affected offspring, and (iii) a replication cohort of 449 African American cases and 480 African American controls. Additionally, a total of 38,714 subjects of European or African descent in 18 independent cohorts with 10 other nonalcoholism neuropsychiatric disorders were analyzed as contrast. Furthermore, 90 unrelated Hap Map CEU individuals, 93 European brain tissue samples, and 80 European peripheral blood mononuclear cell samples underwent cis-acting expression quantitative locus ( cis-e QTL) analysis. Results We identified a significant risk region for alcohol and nicotine codependence between IPO11 and HTR1 A on chromosome 5q that was reported to be suggestively associated with alcohol dependence previously. In the European American discovery cohort, 381 single nucleotide polymorphisms (SNPs) in this region were nominally associated with alcohol and nicotine codependence ( p < 0.05); 57 associations of them survived region- and cohort-wide correction (α = 3.6 × 10−6); and the top SNP (rs7445832) was significantly associated with alcohol and nicotine codependence at the genome-wide significance level ( p = 6.2 × 10−9). Furthermore, associations for 34 and 11 SNPs were replicated in the Australian and African American replication cohorts, respectively. Among these replicable associations, 4 reached genome-wide significance level in the meta-analysis of European Americans and European Australians: rs7445832 ( p = 9.6 × 10−10), rs13361996 ( p = 8.2 × 10−9), rs62380518 ( p = 2.3 × 10−8), and rs7714850 ( p = 3.4 × 10−8). Cis-e QTL analysis showed that many risk SNPs in this region had nominally significant cis-acting regulatory effects on HTR1 A or IPO11 m RNA expression. Finally, no markers were significantly associated with any other neuropsychiatric disorder examined. Conclusions We speculate that this IPO11- HTR1 A region might harbor a causal variant for alcohol and nicotine codependence. [ABSTRACT FROM AUTHOR]

Abstract: The harvest index (HI) of wheat in the high rainfall zones (HRZ) of Australia is low compared with values in similar rainfall environments in Europe. From 2005 to 2007, we examined dry matter (DM) partitioning, yield formation, post-anthesis dry matter accumulation, and remobilization of water soluble carbohydrates (WSC) of a number of wheat genotypes (5 spring wheat and 1 winter wheat) to determine the factors influencing the HI in the HRZ of south-western Australia. Grain yield was strongly correlated with grain number (GN) in all three years and with the sum of post-anthesis DM accumulation and WSC in stems at anthesis when the amount of assimilates available to fill grains was less than 600gm−2. However, when the amount of assimilates exceeded 600gm−2, grain yield reached a plateau and did not increase with the increased availability of assimilates because of sink limitations. Genotypes with more GN tended to extract more WSC to fill grains than ones with fewer GN in 2005 and 2007. GN increased with increased spike DM at anthesis, the number of grainsg−1 of spike DM, and the duration of spike growth, but was not correlated to the fraction of DM partitioned to the spike at anthesis for individual genotypes and across the 3 years. Compared to winter wheat in the UK, Australian spring and winter wheat had a lower number of grainsg−1 spike DM and g−1 chaff DM. HI was positively related to WSC at anthesis and post-anthesis DM accumulation in the drought year of 2006, but not in average (2007) and above-average rainfall (2005) years. HI was negatively related to the proportion of stem DM to above-ground dry matter (AGDM), but positively related to the proportion of spike DM to AGDM. Dry matter partitioning indicated that the proportion of stem DM to AGDM and chaff DM to AGDM was 20% and 50% higher than that of winter wheat grown in the UK, respectively. This was related to a lack of remobilization of WSC and a net increase between spike DM at anthesis and chaff DM at maturity. Therefore, we suggest that increasing the number of grainsm−2 by breeding for more grainsg−1 spike DM, reducing dry matter partitioning into stem and chaff, and remobilizing WSC can lead to an improved HI. We conclude that the yield of wheat can be increased without increasing AGDM and the potential HI can reach 0.50 in the HRZ of south-western Australia if the number of grainsm−2 can be increased. [Copyright &y& Elsevier]

• Multiple-environment trials were used to understand yield and associated traits. • Genotype × environment interaction reveals two environment and four genotype clusters. • Flowering time, biomass and harvest index were the main factors determining yield. • Both specific and broad adaption were identified. Understanding genotype and environment interaction (G × E) and the association between yield and phenological, architectural and physiological traits plays a crucial role in successful canola breeding and agronomic management. We investigated yield performance of 20 open-pollinated and hybrid canola across multiple environments over five years and its association with these traits. Heterogenic genetic variance and genetic correlation among the environments demonstrated significant G × E interactions in yield, biomass, but not in harvest index (HI). Flowering time, biomass at maturity and HI are the three most important traits underlying the G × E interaction. Principal component analysis (PCA) based on the yield across the environments identified two mega-environments (the low/medium rainfall zone (LMRZ) and the high rainfall zone (HRZ)) and four genotype clusters (early-flowering, late-flowering, average performing, and broadly adapted varieties). Early flowering genotypes were better adapted to the LMRZ mega-environment and late-flowering ones to the HRZ mega-environment. Despite the G × E interaction, a group of hybrid varieties were identified as broadly adapted, producing either the highest or similar yield to specifically adapted varieties. The genotype by trait PCA revealed that yield was positively associated with biomass and HI but negatively with flowering time in the LMRZ mega-environment. In contrast, yield was positively associated with increased biomass, late-flowering but negatively with HI in the HRZ mega-environment. In both mega-environments, HI was negatively correlated with delay in flowering and increased plant height and biomass. Reducing plant height in late flowering hybrid varieties offers a solution to the trade-off between biomass and HI. It can have the potential to increase yield by increasing HI while maintaining biomass in the HRZ mega-environment. [ABSTRACT FROM AUTHOR]

• Grain number (GN) is modelled by spike growth rate (SGR), fruiting efficiency (FE) and the duration of spike growth (D s). • The ranking of their relative contribution to GN is SGR > FE > D s. • The yield benefit of increasing grain number depends on the availability of source. Grain number (GN) is determined by spike growth rate (SGR), fruiting efficiency (FE) and the duration of spike growth period (D s). However, these three traits are not independent of each other and therefore quantifying their relative contribution to GN is important for improving yield potential. This study aimed to model GN as a function of SGR, FE and D s in bread wheat and investigate the relative importance of these three traits in determining GN. A large number of commercial varieties, elite wheat breeding lines, and a Multiparent Advanced Generation InterCross population were evaluated for GN, SGR, D s , and FE in six Australian environments in 2014 and 2015. The model explained 43–98% of the variation in GN in individual environments and 88% of the variation in GN across the six environments. The percentage of GN variance explained by the model was significantly higher than those explained by correlating GN to individual traits. The relative importance of the contribution of the three traits to GN was different and ranked as SGR > FE > D s. The negative correlation between FE and spike dry weight at anthesis (SDW a) appears to be spurious, suggesting that there was no causality between high FE and low SDWa and vice versa. Thus, FE can be used as an independent trait to increase GN in addition to SGR and D s. We also investigated if the wheat crop had enough source to fill the increased sink size in the southern Australian high rainfall environment. The source-sink balance analysis indicates that the available source, consisting of concurrent photosynthetic assimilate and stored water-soluble carbohydrate at anthesis, was sufficient to fill the established sink but no surplus assimilates were available to fill a larger sink in southwestern Australia. However, the opportunity to increase yield potential by further increasing grain number might exist in south-eastern Australia environments. [ABSTRACT FROM AUTHOR]

• Increased vernalisation requirement of canola proposed as mechanism to improve yield. • Spatial modelling shows yield advantage in 3.7 Mha from increased vernalisation. • New winter × spring crosses could lift canola production by 10% in Southern Australia. • Winter × spring canola lines provide intermediate maturity between spring and winter types. • Longer season canola will provide opportunities for earlier sowing of crops. Long season, winter-type canola cultivars have the potential for significantly higher yields than short-season, spring-type canola, yet until recently, breeding of new canola cultivars in Australia has focussed on spring-type canola. This has been to accommodate the typically drier, warmer conditions across the Australian cropping belt where long-season varieties do not perform well due to delayed flowering and risk of water-stress during grain fill. However, as cropping continues to expand into the Australian High Rainfall Zone (500–900 mm, HRZ), breeders have become increasingly interested in developing winter-spring crosses (not yet commercially available) which have an intermediate phenology between that of a spring and winter-type canola. As the vernalisation requirement for these crosses is lower than winter-type canola, the areas where such cultivars can be grown profitably in Australia is potentially much wider than for winter-type canola. Field experimentation and crop simulation studies across the potential cropping region of southern Australia were used to determine the yield potential of these winter-spring canola crosses compared with currently available spring-type and winter-type cultivars. Our analysis showed that the four winter-spring crosses evaluated had a range of vernalisation requirements which were between the small requirements of spring-types and the large requirement of winter-types. In this study the Catchment Analysis Tool (CAT) spatial modelling framework was used to determine the expected canola yields of four cultivars across the entire cropping region of southern Australia. These cultivars were the spring-type 45Y88CL, winter-type Hyola® 970CL and two winter-spring crosses K50057 and K50058 with vernalisation requirements at the higher end and the lower end of the range of winter-spring crosses, respectively. The potential benefit of some increase in the vernalisation requirement, based on the area currently sown to canola, was an additional 381 M tonnes per year (based on 50-year average) of canola, if K50058 was sown in areas where it proved superior to 45Y88CL. At the 5-year average canola price of $486 t−1, this would provide an additional AUD 185 Mil/annum for the industry. In general, the modelled yield advantage from canola cultivars with increased vernalisation requirement was greater in the areas of southern Australia that had milder climates and higher rainfall. The value to the Australian canola industry of substituting spring cultivars (e.g. 45Y88CL) with winter x spring (K50057) or winter (Hyola970CL) cultivars where they had a yield advantage, was AUD 82.8 M and AUD 29.2 M, respectively. [ABSTRACT FROM AUTHOR]

• Photo-period corrected thermal time integrated with wheat allelic information has advanced phenology prediction. • Allelic based phenological models define allelic combinations which maximized yield stability in specific environments. • Allelic based phenological models can accelerate the release of better adapted germplasm to new and changing environments. We developed a photoperiod-corrected thermal model that can predict wheat phenology based solely on the combination of photoperiod (Ppd) and vernalisation (Vrn) alleles to identify the phenological suitability of germplasm across the cropping region in southern Australia. More than 200 wheat genotypes that vary in combinations of Ppd and Vrn alleles were grown at 17 locations spanning 11° Latitude, thus providing a wide range in temperature and daylength gradients. The phenological sensitivities of a genotype to varying basic temperature, photoperiod and vernalisation requirement was adjusted via optimisation to minimise the least square difference between the measured and predicted dates of both terminal spike (TS) and flowering (AN). The model predicted dates of TS and AN to within 5 days of the field values. Information was used to identify the alleles required to achieve a wheat ideotype defined in a previous study. The optimum allelic combinations required to target the optimum flowering period for different locations when sown on different dates were also identified. The use of allelic based phenological models has the potential to reduce the costs to breeding programs and accelerate the release of better adapted germplasm to new and changing environments. [ABSTRACT FROM AUTHOR]

Objectives: We have previously reported a top-ranked risk gene [i.e., serine incorporator 2 gene (SERINC2)] for alcohol dependence in individuals of European descent by analyzing the common variants in a genome-wide association study. In the present study, we comprehensively examined the rare variants [minor allele frequency (MAF)<0.05] in the NKAIN1-SERINC2 region to confirm our previous finding., Materials and Methods: A discovery sample (1409 European-American patients with alcohol dependence and 1518 European-American controls) and a replication sample (6438 European-Australian family participants with 1645 alcohol-dependent probands) were subjected to an association analysis. A total of 39,903 individuals from 19 other cohorts with 11 different neuropsychiatric and neurological disorders served as contrast groups. The entire NKAIN1-SERINC2 region was imputed in all cohorts using the same reference panels of genotypes that included rare variants from the whole-genome sequencing data. We stringently cleaned the phenotype and genotype data, and obtained a total of about 220 single-nucleotide polymorphisms in individuals of European descent and about 450 single-nucleotide polymorphisms in the individuals of African descent with 0

Aims: Some of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference., Methods: A total of 49,358 subjects in 22 independent cohorts with 11 different neuropsychiatric and neurological disorders were analyzed, including 3 cohorts with alcohol dependence. The entire ADH gene cluster (ADH7-ADH1C-ADH1B-ADH1A-ADH6-ADH4-ADH5 at Chr4) was imputed in all samples using the same reference panels that included whole-genome sequencing data. We stringently cleaned the phenotype and genotype data to obtain a total of 870 single nucleotide polymorphisms with 0< MAF <0.05 for association analysis., Results: We found that a rare variant constellation across the entire ADH gene cluster was significantly associated with alcohol dependence in European-Americans (Fp1: simulated global P = 0.045), European-Australians (Fp5: global P = 0.027; collapsing: P = 0.038) and African-Americans (Fp5: global P = 0.050; collapsing: P = 0.038), but not with any other neuropsychiatric disease. Association signals in this region came principally from ADH6, ADH7, ADH1B and ADH1C. In particular, a rare ADH6 variant constellation showed a replicable association with alcohol dependence across these three independent cohorts. No individual rare variants were statistically significantly associated with any disease examined after group- and region-wide correction for multiple comparisons., Conclusion: We conclude that rare ADH variants are specific for alcohol dependence. The ADH gene cluster may harbor a causal variant(s) for alcohol dependence.