Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Antimicrobial efficacy of cinnamon, ginger, horseradish and nutmeg extracts against spoilage pathogens

In the search for alternatives to the use of synthetic fungicides, aqueous spice extracts were evaluated for their effects on the mycelial growth of various spoilage pathogens and their ability to control potato dry rot and carrot cavity spot in vivo. Results showed that cinnamon, ginger and nutmeg significantly inhibited the mycelial growth of Aspergillus niger (Ascomycota), Fusarium sambucinum (Ascomycota), Pythium sulcatum (Oomycota) or Rhizopus stolonifer (Zygomycota), whereas horseradish extract did not lead to the inhibition of any microorganism at the tested concentration. Among the most effective extracts, 0.05 g mL-1 of cinnamon extract completely inhibited A. niger and P. sulcatum, and 0.10 g mL-1 of cinnamon extract completely inhibited F. sambucinum. A concentration of 0.05 g mL -1 of ginger extract also caused 100% inhibition of P. sulcatum. In vivo, cinnamon extract significantly reduced lesions of potato dry rot and carrot cavity spot, and ginger extract reduced lesions of carrot cavity spot. These results indicate that aqueous cinnamon and ginger extracts could provide an alternative to the use of synthetic fungicides to control these pathogens

Antimicrobial efficacy of cinnamon, ginger, horseradish and nutmeg extracts against spoilage pathogens

In the search for alternatives to the use of synthetic fungicides, aqueous spice extracts were evaluated for their effects on the mycelial growth of various spoilage pathogens and their ability to control potato dry rot and carrot cavity spot in vivo. Results showed that cinnamon, ginger and nutmeg significantly inhibited the mycelial growth of Aspergillus niger (Ascomycota), Fusarium sambucinum (Ascomycota), Pythium sulcatum (Oomycota) or Rhizopus stolonifer (Zygomycota), whereas horseradish extract did not lead to the inhibition of any microorganism at the tested concentration. Among the most effective extracts, 0.05 g mL-1 of cinnamon extract completely inhibited A. niger and P. sulcatum, and 0.10 g mL-1 of cinnamon extract completely inhibited F. sambucinum. A concentration of 0.05 g mL -1 of ginger extract also caused 100% inhibition of P. sulcatum. In vivo, cinnamon extract significantly reduced lesions of potato dry rot and carrot cavity spot, and ginger extract reduced lesions of carrot cavity spot. These results indicate that aqueous cinnamon and ginger extracts could provide an alternative to the use of synthetic fungicides to control these pathogens

Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families

Sotakarjut : Roolipelin visuaalinen taide ja ammatillinen vuorovaikutus projektityöympäristössä.

Opinnäytetyöni pohjautuu vuonna 2012 julkaistavaan roolipelikirjaan nimeltä Sotakarjut. TAMKista valmistuvana visuaalisena suunnittelijana olin mukana piirtämässä sekä konseptitaiteidetta, että kuvituskuvia kyseistä teosta varten. Kyseisen projektin aikana työskentelin sekä taiteellisen johdon alaisuudessa, että osana useamman kuvittajan/konseptitaiteilijan muodostamaa työryhmää, jolloin taiteellisesta ja ammatillisesta vuorovaikutuksesta tuli selkeä osa projektin kulkua. Näistä lähtökohdista päätin myös kirjoittaa opinnäytetyöni kirjallisen osuuden. Opinnäytetyöni tarkoitus on valaista monin tavoin vuorovaikutteiseksi muodostuvien projektityöympäristöjen vaikutusta taiteilijaan niin kuvittajan, kuin konseptitaiteilijan ammattissa. Valitsemaani aihetta lähestyn tekemäni projektin rajaaman kontekstin sisällä käymällä aluksi läpi nämä kaksi visuaalisen suunnittelun ammattihaaraa kartoittamalla taiteilijan roolia osana laajempaa projektityöympäristöä, ja tarjoamalla käytännön kautta lähestyvää näkökantaa esittelemilleni asioille. Tutkin sekä ulkoisen, että sisäisen vuorovaikutuksen merkitystä ja niiden luomia mahdollisuuksia luovalla alalla toimivan taiteilijan näkökulmasta. Esitän myös käytännön tapoja siitä, miten nämä vuorovaikutukselliset elementit voidaan valjastaa palvelemaan yksilön omaa ammatillista ja taiteellista kehitystä.My thesis work is based on a traditional role-playing-game that is set to be published in the year 2012, a book titled Sotakarjut. About to graduate from TAMK, Tampere University of Applied Sciences, as a visual designer I took part in this project, in a role that covered two distinct fields of profession: concept art and a illustration. As an single artist I worked under a artistic supervision and within a project that had several illustrators/consept artist in its ranks, thus making it essential to work as a singular creative team. In this thesis I will try to shed some light on how project-related work enviroments involves a specific kind of artististic approach from professional consept artists and illustrators. Having my project part work as my general context, I will start by making a general introduction on both of these creative professions, giving an overview on the subject of artististic work within project enviroments. I will also present a practical approach by adding examples from my actual project to support the theory based information I am presenting. In addition I will write about the many effects that professional interaction has within a working eviroment, from the artist view-point. Through this I will also explain how it is possible to assert yourself as a professional artist, so that this interaction can be made beneficial to the indivudual, both artistically and professional

Genome-wide and fine-resolution association analysis of malaria in West Africa

We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations