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Genome-wide association studies (GWASs) have uncovered a wealth of associations between common variants and human phenotypes. Here, we present an integrative analysis of GWAS summary statistics from 36 phenotypes to decipher multitrait genetic architecture and its link with biological mechanisms. Our framework incorporates multitrait association mapping along with an investigation of the breakdown of genetic associations into clusters of variants harboring similar multitrait association profiles. Focusing on two subsets of immunity and metabolism phenotypes, we then demonstrate how genetic variants within clusters can be mapped to biological pathways and disease mechanisms. Finally, for the metabolism set, we investigate the link between gene cluster assignment and the success of drug targets in randomized controlled trials., Competing Interests: The authors have declared that no competing interests exist.

Genome-wide association study (GWAS) has been the driving force for identifying association between genetic variants and human phenotypes. Thousands of GWAS summary statistics covering a broad range of human traits and diseases are now publicly available. These GWAS have proven their utility for a range of secondary analyses, including in particular the joint analysis of multiple phenotypes to identify new associated genetic variants. However, although several methods have been proposed, there are very few large-scale applications published so far because of challenges in implementing these methods on real data. Here, we present JASS (Joint Analysis of Summary Statistics), a polyvalent Python package that addresses this need. Our package incorporates recently developed joint tests such as the omnibus approach and various weighted sum of Z -score tests while solving all practical and computational barriers for large-scale multivariate analysis of GWAS summary statistics. This includes data cleaning and harmonization tools, an efficient algorithm for fast derivation of joint statistics, an optimized data management process and a web interface for exploration purposes. Both benchmark analyses and real data applications demonstrated the robustness and strong potential of JASS for the detection of new associated genetic variants. Our package is freely available at https://gitlab.pasteur.fr/statistical-genetics/jass., (© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Objectives: Malnutrition and functional decline are common in older inpatients admitted to subacute care settings. However the association between changes in nutritional status and relevant functional outcomes remains under-researched. This study examined changes in nutritional status, function and mobility in patients admitted to a Geriatric Evaluation and Management (GEM) unit who had a length of stay (LOS) longer than 21 days., Design: A prospective, observational study., Setting: Two GEM units at St Vincent's Hospital Melbourne, Australia., Participants: Patients admitted to the GEM units who stayed longer than 21 days were included in the study., Measurements: Patients were assessed on admission and prior to discharge using the Subjective Global Assessment (SGA), Functional Independence Measure (FIM) motor domain and the Modified Elderly Mobility Scale (MEMS)., Results: Fifty-nine patients (Mean age 84.0 ± 7 years) met the required length of stay and were included in the study. Fifty-four per cent (n=32) were malnourished on admission (SGA B/C) and 44% (n=26) were malnourished on discharge. Twenty-two per cent (n=13) improved SGA category, 75% remained stable (n=44) and 3% deteriorated (n=2) from admission to discharge. Total Motor FIM scores significantly increased from admission to discharge in both the improved (p<0.001) and stable or deteriorated (p<0.001) nutritional status groups. Subjects who improved in nutritional status had a significantly higher MEMS score at discharge (p<0.001)., Conclusion: On admission to the GEM unit, just over half the included patients were rated as malnourished defined by SGA category. Nearly one quarter of the sample had improved their nutritional status at the time of discharge. Improvement in nutritional status was associated with greater improvement in mobility scores. Further studies are required to investigate the effectiveness of nutrition interventions, which will inform models of care aiming to optimise nutritional, functional, and associated clinical outcomes in patients admitted to GEM units., Competing Interests: The authors declare no conflict of interest.

Patellar disequilibrium consists of either external malpositioning of the patella (EMP) or external hyperpression (EHP), which are clearly visible on a 30degrees axial radiograph of the knee. Does this disequilibrium play a role in the development of patellar chondropathy? The authors have based their comparisons on a series of 40 subjects more than 60 years of age (average age: 68 years) who were free from pain and arthrosis of the knee. In this group they found 2 cases of EMP (5 percent) and 3 of EHP (7.5 percent). In their series of cases of patellar chondropathy (43 cases) there were, after correction for the cases with a double etiology, 8.5 cases of EMP (20 percent) and 7 of EHP (16 percent). The differences between these figures and those for the control series are statistically significant for the number of cases of EMP (P less than 0.05), but not for the number of cases of EHP, the etiological role of which is probable but for which proof would require a larger series of patients. From this work the following findings emerge: (1) The frequency of latent patellofemoral arthrosis in the aged control subjects with knee problems. 7 cases out of 47, or 12.5 percent. (2) The frequency of patellar chondropathy apparently associated with the two etiological factors: out of 43 patients, 22 suffered from patellar disequilibrium (10 EMP and 12 EHP) but in 13 cases there was another associated possible cause of deterioration: traumatism or stress on the knee associated with work or sport. This methodological difficulty is discussed and resolved empirically. The importance of patellar disequilibrium in the development of degenerative patellofemoral affections derives not from the etiological importance but from the fact that they represent the only factor for which therapy may be given: elective internal rehabilitation or surgery (section of the external wing of the patella or transposition of the anterior tuberosity of the tibia).