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Sökning: WFRF:(Crosbie J)

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  • O'Dushlaine, C, et al. (författare)
  • Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
  • 2015
  • Ingår i: Nature neuroscience. - 1546-1726. ; 18:2, s. 199-209
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
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  • Lee, S. Hong, et al. (författare)
  • Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
  • 2013
  • Ingår i: Nature genetics. - 1546-1718. ; 45:9, s. 984-
  • Tidskriftsartikel (refereegranskat)abstract
    • Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders. © 2013 Nature America, Inc. All rights reserved.
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  • Crosbie, J. C., et al. (författare)
  • Reference dosimetry at the Australian Synchrotron's imaging and medical beamline using free-air ionization chamber measurements and theoretical predictions of air kerma rate and half value layer
  • 2013
  • Ingår i: Medical physics (Lancaster). - 0094-2405. ; 40:6, s. 062103
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Purpose: Novel, preclinical radiotherapy modalities are being developed at synchrotrons around the world, most notably stereotactic synchrotron radiation therapy and microbeam radiotherapy at the European Synchrotron Radiation Facility in Grenoble, France. The imaging and medical beamline (IMBL) at the Australian Synchrotron has recently become available for preclinical radiotherapy and imaging research with clinical trials, a distinct possibility in the coming years. The aim of this present study was to accurately characterize the synchrotron-generated x-ray beam for the purposes of air kerma-based absolute dosimetry. Methods: The authors used a theoretical model of the energy spectrum from the wiggler source and validated this model by comparing the transmission through copper absorbers (0.1-3.0 mm) against real measurements conducted at the beamline. The authors used a low energy free air ionization chamber (LEFAC) from the Australian Radiation Protection and Nuclear Safety Agency and a commercially available free air chamber (ADC-105) for the measurements. The dimensions of these two chambers are different from one another requiring careful consideration of correction factors. Results: Measured and calculated half value layer (HVL) and air kerma rates differed by less than 3% for the LEFAC when the ion chamber readings were corrected for electron energy loss and ion recombination. The agreement between measured and predicted air kerma rates was less satisfactory for the ADC-105 chamber, however. The LEFAC and ADC measurements produced a first half value layer of 0.405 ± 0.015 and 0.412 ± 0.016 mm Cu, respectively, compared to the theoretical prediction of 0.427 ± 0.012 mm Cu. The theoretical model based upon a spectrum calculator derived a mean beam energy of 61.4 keV with a first half value layer of approximately 30 mm in water. Conclusions: The authors showed in this study their ability to verify the predicted air kerma rate and x-ray attenuation curve on the IMBL using a simple experimental method, namely, HVL measurements. The HVL measurements strongly supports the x-ray beam spectrum, which in turn has a profound effect on x-ray dosimetry.</p>
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