Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor

Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia

Amyotrophic Lateral Sclerosis (ALS) is recognised to be a complex neurodegenerative disease involving both genetic and non-genetic risk factors. The underlying causes and risk factors for the majority of cases remain unknown; however, ever-larger genetic data studies and methodologies promise an enhanced understanding. Recent analyses using published summary statistics from the largest ALS genome-wide association study (GWAS) (20,806 ALS cases and 59,804 healthy controls) identified that schizophrenia (SCZ), cognitive performance (CP) and educational attainment (EA) related traits were genetically correlated with ALS. To provide additional evidence for these correlations, we built single and multi-trait genetic predictors using GWAS summary statistics for ALS and these traits, (SCZ, CP, EA) in an independent Australian cohort (846 ALS cases and 665 healthy controls). We compared methods for generating the risk predictors and found that the combination of traits improved the prediction (Nagelkerke-R2) of the case–control logistic regression. The combination of ALS, SCZ, CP, and EA, using the SBayesR predictor method gave the highest prediction (Nagelkerke-R2) of 0.027 (P value = 4.6 × 10−8), with the odds-ratio for estimated disease risk between the highest and lowest deciles of individuals being 3.15 (95% CI 1.96–5.05). These results support the genetic correlation between ALS, SCZ, CP and EA providing a better understanding of the complexity of ALS

Relationships between grain yield and accumulation of biomass, nitrogen and phosphorus in common bean cultivars Relações entre o rendimento de grãos e a acumulação de biomassa, nitrogênio e fósforo em cultivares de feijoeiro

Shoot biomass is considered a relevant component for crop yield, but relationships between biological productivity and grain yield in legume crops are usually difficult to establish. Two field experiments were carried out to investigate the relationships between grain yield, biomass production and N and P accumulation at reproductive stages of common bean (Phaseolus vulgaris) cultivars. Nine and 18 cultivars were grown on 16 m² plots in 1998 and 1999, respectively, with four replications. Crop biomass was sampled at four growth stages (flowering R6, pod setting R7, beginning of pod filling R8, and mid-pod filling R8.5), grain yield was measured at maturity, and N and P concentrations were determined in plant tissues. In both years, bean cultivars differed in grain yield, in root mass at R6 and R7 stages, and in shoot mass at R6 and R8.5, whereas at R7 and R8 differences in shoot mass were significant in 1998 only. In both years, grain yield did not correlate with shoot mass at R6 and R7 and with root mass at R6. Grain yield correlated with shoot mass at R8 in 1999 but not in 1998, with shoot mass at R8.5 and with root mass at R7 in both years. Path coefficient analysis indicated that shoot mass at R8.5 had a direct effect on grain yield in both years, that root mass at R7 had a direct effect on grain yield in 1998, and that in 1999 the amounts of N and P in shoots at R8.5 had indirect effects on grain yield via shoot mass at R8.5. A combined analysis of both experiments revealed that biomass accumulation, N and P in shoots at R6 and R7 as well as root mass at R6 were similar in both years. In 1998 however bean accumulated more root mass at R7 and more biomass and N and P in shoots at R8 and R8.5, resulting in a 57 % higher grain yield in 1998. This indicates that grain yield of different common bean cultivars is not intrinsically associated with vegetative vigor at flowering and that mechanisms during pod filling can strongly influence the final crop yield. The establishment of a profuse root system during pod setting, associated with the continuous N and P acquisition during early pod filling, seems to be relevant for higher grain yields of common bean.<br>A biomassa de parte aérea é considerada um componente relevante para o rendimento dos cultivos, mas é usualmente difícil estabelecer relações entre produção biológica e rendimento de grãos em leguminosas. Foram realizados dois experimentos de campo com o objetivo de investigar as relações entre o rendimento de grãos, a produção de biomassa e a acumulação de N e P em estádios reprodutivos de cultivares de feijoeiro (Phaseolus vulgaris). Nove e 18 cultivares foram cultivadas em 1998 e 1999, respectivamente, em parcelas de 16 m² com quatro repetições. A biomassa foi amostrada em quatro estádios (floração R6, emissão de vagens R7, início de enchimento de vagens R8 e meio de enchimento de vagens R8,5), o rendimento de grãos mensurado na maturação, e foram medidas as concentrações de N e P nos tecidos vegetais. Nos dois anos, as cultivares de feijoeiro diferiram no rendimento de grãos, na massa de raízes nos estádios R6 e R7 e na massa de parte aérea em R6 e R8,5, porém em R7 e R8 apenas em 1998 houve diferenças na massa de parte aérea. Nos dois anos, o rendimento de grãos não se correlacionou com a massa de parte aérea em R6 e R7 e com a massa de raízes em R6. O rendimento de grãos correlacionou-se com a massa de parte aérea em R8 em 1999, com a massa de parte aérea em R8,5 e com a massa de raízes em R7 nos dois anos. Análises de trilha indicaram que a massa de parte aérea em R8,5 exerceu efeito direto no rendimento de grãos nos dois anos, que a massa de raízes em R7 teve efeito direto no rendimento em 1998 e que em 1999 a acumulação de N e P na parte aérea em R8,5 teve efeito indireto no rendimento via massa de parte aérea em R8,5. A análise conjunta dos dois experimentos revelou que a acumulação de massa, N e P na parte aérea em R6 e R7, assim como a massa de raízes em R6, foram similares nos dois anos, mas em 1998 o cultivo acumulou mais massa de raízes em R7 e mais massa, N e P na parte aérea em R8 e R8,5, o que resultou em produção de grãos 57 % superior em 1998. Isso indica que o rendimento de grãos de cultivares de feijoeiro não está intrinsecamente associado com o vigor vegetativo na floração e que mecanismos operantes durante o enchimento das vagens podem influenciar acentuadamente a produção de grãos. O estabelecimento de um profuso sistema radicular durante a emissão de vagens, associado com a contínua aquisição de N e P durante o início de enchimento de vagens, pode assumir relevância para obtenção de maiores rendimentos de grãos na cultura do feijão

Morphological analysis of the corneal endothelium in eyes of dogs using specular microscopy Análise morfológica com microscopia especular do endotélio corneal em olhos de cães

Both healthy eyes of 10 six-year-old male and female mongrel dogs were studied. With a contact specular microscope the corneal endothelium was examined. Endothelial cells were analyzed in the central and peripheral cornea. Morphological analysis with regard to polymegathism and pleomorphism was performed. Three images of each region with at least 100 cells were obtained. The analysis showed that polygonal cells formed a mosaic-like pattern uniform in size and shape. The predominant number of cells was hexagonal. The polymegathism index was 0.22. The study demonstrates that the morphology of the normal corneal endothelial cells of dogs is similar to that found in the human cornea.<br>Foram estudados 20 olhos de 10 cães sem raça definida, machos e fêmeas com 6 anos de idade. A morfologia das células do endotélio da córnea foi analisada utilizando-se microscópio especular de contato. Foram estudadas as regiões central e periférica da córnea. De cada região da córnea foram realizadas três micrografias. De cada micrografia foram analisadas no mínimo 100 células endoteliais. Foram obtidos os valores do polimegatismo e pleomorfismo. O endotélio corneano de cães caracterizou-se por uma monocamada de células poligonais uniformes em tamanho e forma. A forma predominante das células endoteliais foi hexagonal. O índice de polimegatismo foi 0.22. Este estudo demonstrou que a morfologia das células do endotélio da córnea de cães é semelhante à observada em humanos