| 1. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- 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 (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 2. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 3. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 4. |
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| 5. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 6. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 7. |
- Bennett, Gareth J., et al.
(författare)
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Modelling multi-modal sound transmission from point sources in ducts with flow using a wave-based method
- 2009
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Ingår i: 16th International Congress on Sound and Vibration, ICSV16. - 9781615677368 ; , s. 4685-4693
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- An understanding of the multi-modal propagation of acoustic waves in ducts is of practical interest for use in the control of noise in, for example, aero-engines, automotive exhaust and ventilation systems. In this paper, the propagation of sound from point sources in hard-walled ducts is modelled using a numerical wave-based approach, referred to as the wave expansion method. This is a highly efficient full-domain discretisation method, which requires as few as two-to-three mesh points per wavelength. An inhomogeneous potential flow may be easily included in the method. The numerical solution for point sources embedded in the wall of a circular duct with non-reflective end-conditions and a uniform axial flow is compared with an analytical Green's function solution. A modal decomposition technique is used to provide detailed information about the modal content of the sound field. This study provides an insightful comparison between an analytical and numerical solution to the acoustic field in a duct. The accuracy and robustness of the wave expansion method is assessed for this benchmark problem before its versatility is demonstrated with examples.
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| 8. |
- Bennett, Gareth J., et al.
(författare)
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Noise source location in turbomachinery using coherence based modal decomposition
- 2009
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Ingår i: 15th AIAA/CEAS Aeroacoustics Conference (30th AIAA Aeroacoustics Conference). - Reston, Virigina : American Institute of Aeronautics and Astronautics. - 9781563479748
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Coherence based source analysis techniques can be used to identify the contribution of turbomachinery core noise sources to pressure measurements in the far-field. The usual approach is to locate a measurement sensor within the engine and to calculate the ordinary coherence function between this and the far-field pressure measurement. If the internal measurement is close to a dominant noise source, the technique will identify this sources' contribution to the overall far-field energy. Modal decomposition is an advanced technique which can provide detailed information as to the modal content of sound propagating in ducts. When applied to aero-engines, the technique can be used as a diagnostic to determine which of the many rotor-stator stages contribute most to the overall radiated sound power. The method developed in this paper discusses how the two techniques can be combined to locate the plane at which a mode is generated within an aeroengine. A proof of concept of the technique is successfully demonstrated with the use of simulated data.
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| 9. |
- Neri, Eleonora, et al.
(författare)
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Characterization of low noise technologies applied to a full scale fuselage mounted nose landing gear
- 2015
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Ingår i: 44th International Congress and Exposition on Noise Control Engineering, INTER-NOISE. - : The American Society of Mechanical Engineers (ASME). - 9780791856819 ; , s. 1869-1878
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The negative impact of aircraft noise includes effects on population's health, land use planning and economic issues such as building restrictions and operating restrictions for airports. Thus, the reduction of noise generated by aircraft at take-off and approach is an essential consideration in the development of new commercial aircraft. Among the different aircraft noise sources, landing gear noise is one of the most significant during approach. This research presents results from the European Clean Sky funded ALLEGRA project, which investigated a full-scale Nose Landing Gear (NLG) model featuring the belly fuselage, bay cavity and hydraulic dressing. Tests were performed for a variety of wind speeds and yaw angles. In this paper, a characterization of the noise generated by the full-scale Nose Landing Gear (NLG) model is presented and the different techniques used for characterizing acoustic sources on the NLG are described. The landing gear noise source is characterized in terms of OASPL, directivity, source spectra, PNL and PNLT. A comparison between the NLG with and without the application of low noise technology is presented.
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