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Sökning: WFRF:(Kahn RS)

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  • Adams, Hieab H. H., et al. (författare)
  • Novel genetic loci underlying human intracranial volume identified through genome-wide association
  • 2016
  • Ingår i: Nature Neuroscience. - 1097-6256 .- 1546-1726. ; 19:12, s. 1569-1582
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
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  • Adcox, K, et al. (författare)
  • PHENIX detector overview
  • 2003
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier. - 0167-5087. ; 499:2-3, s. 469-479
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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  • Fleischhacker, W Wolfgang, et al. (författare)
  • Metabolic risk factors in first-episode schizophrenia : baseline prevalence and course analysed from the European First-Episode Schizophrenia Trial
  • 2013
  • Ingår i: International Journal of Neuropsychopharmacology. - 1461-1457 .- 1469-5111. ; 16:5, s. 987-995
  • Tidskriftsartikel (refereegranskat)abstract
    • Available data on antipsychotic-induced metabolic risks are often constrained by potential confounding effects due to prior antipsychotic treatment. In this study, we assessed the baseline prevalence of metabolic abnormalities and changes following treatment with five commonly-used antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine or ziprasidone) in first-episode, partially antipsychotic-naive patients with schizophrenia in the European first-episode schizophrenia trial (EUFEST). Overall baseline prevalence of metabolic syndrome (MetS) was 6.0%, with similar rates observed in the antipsychotic-naive patients (5.7%, 9/157) and in the other patients with only a brief prior exposure to antipsychotics (6.1%, 20/326). These results are consistent with the MetS prevalence rate estimated in a general population of similar age. Examination of individual risk factors showed 58.5% of subjects had one or more elevated metabolic risks at baseline: 28.5% demonstrated suboptimal HDL; 24.2% hypertension; 17.7% hypertriglyceridemia; 8.2% abdominal obesity; 7.3% hyperglycaemia. Increase in body weight (kg/month) occurred in patients treated with haloperidol (0.62 s.e. 0.11), amisulpride (0.76 s.e. 0.08), olanzapine (0.98 s.e. 0.07) and quetiapine (0.58 s.e. 0.09), which was significantly greater than that in the ziprasidone group (0.18 s.e. 0.10). The incidence rate of new diabetes cases over a 52-wk follow-up period was 0.82% (4/488). More patients experienced worsening rather than improvement of hypertriglyceridemia or hyperglycaemia in all treatment groups. Our findings suggest that in first-episode, partially antipsychotic-naive patients, the baseline prevalence rate of MetS appears to be no higher than that in the general population, but serious underlying individual risk factors nevertheless existed.
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9.
  • Grasby, KL, et al. (författare)
  • The genetic architecture of the human cerebral cortex
  • 2020
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 367:6484, s. 1340-
  • Tidskriftsartikel (refereegranskat)
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10.
  • Hibar, Derrek P., et al. (författare)
  • Common genetic variants influence human subcortical brain structures
  • 2015
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 520:7546, s. 224-U216
  • Tidskriftsartikel (refereegranskat)abstract
    • The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
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