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138 results on '"Memari, Y."'

1. The QUaD Galactic Plane Survey II: A Compact Source Catalog

Author: Culverhouse, T., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Friedman, R., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Pryke, C., Schwarz, R., O'Sullivan, C., Piccirillo, L., Rajguru, N., Rusholme, B., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract: We present a catalog of compact sources derived from the QUaD Galactic Plane Survey. The survey covers ~800 square degrees of the inner galaxy (|b|<4 degrees) in Stokes I, Q and U parameters at 100 and 150 GHz, with angular resolution 5 and 3.5 arcminutes. 505 unique sources are identified in I, of which 239 are spatially matched between frequency bands, with 50 (216) detected at 100 (150) GHz alone; 182 sources are identified as ultracompact HII (UCHII) regions. Approximating the distribution of total intensity source fluxes as a power-law, we find a slope of $\gamma_{S,100}=-1.8\pm0.4$ at 100 GHz, and $\gamma_{S,150}=-2.2\pm0.4$ at 150 GHz. Similarly, the power-law index of the source two-point angular correlation function is $\gamma_{\theta,100}=-1.21\pm0.04$ and $\gamma_{\theta,150}=-1.25\pm0.04$. The total intensity spectral index distribution peaks at $\alpha_{I}\sim0.25$, indicating that dust emission is not the only source of radiation produced by these objects between 100 and 150 GHz; free-free radiation is likely significant in the 100 GHz band. Four sources are detected in polarized intensity P, of which three have matching counterparts in I. Three of the polarized sources lie close to the galactic center, Sagittarius A*, Sagittarius B2 and the Galactic Radio Arc, while the fourth is RCW 49, a bright HII region. An extended polarized source, undetected by the source extraction algorithm on account of its $\sim0.5^{\circ}$ size, is identified visually, and is an isolated example of large-scale polarized emission oriented distinctly from the bulk galactic dust polarization., Comment: 30 pages, 19 figures, two catalogs; submitted to ApJS; maps and catalogs downloadable from
Published: 2010
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2. The QUaD Galactic Plane Survey 1: Maps And Analysis of Diffuse Emission

Author: Culverhouse, T., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Friedman, R., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Schwarz, R., Sullivan, C. O', Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: Astrophysics - Astrophysics of Galaxies
Abstract: We present a survey of ~800 square degrees of the galactic plane observed with the QUaD telescope. The primary product of the survey are maps of Stokes I, Q and U parameters at 100 and 150 GHz, with spatial resolution 5 and 3.5 arcminutes respectively. Two regions are covered, spanning approximately 245-295 and 315-5 degrees in galactic longitude l, and -4
Published: 2010
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3. Parameter Estimation from Improved Measurements of the CMB from QUaD

Author: QUaD collaboration, Gupta, S., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Friedman, R. B., Ganga, K., Gear, W. K., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., O'Sullivan, C., Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract: We evaluate the contribution of cosmic microwave background (CMB) polarization spectra to cosmological parameter constraints. We produce cosmological parameters using high-quality CMB polarization data from the ground-based QUaD experiment and demonstrate for the majority of parameters that there is significant improvement on the constraints obtained from satellite CMB polarization data. We split a multi-experiment CMB dataset into temperature and polarization subsets and show that the best-fit confidence regions for the LCDM 6-parameter cosmological model are consistent with each other, and that polarization data reduces the confidence regions on all parameters. We provide the best limits on parameters from QUaD EE/BB polarization data and we find best-fit parameters from the multi-experiment CMB dataset using the optimal pivot scale of k_p=0.013 Mpc-1 to be {omch2, ombh2, H_0, A_s, n_s, tau}= {0.113, 0.0224, 70.6, 2.29 times 10^-9, 0.960, 0.086}., Comment: 7 pages, 5 figures, updated to reflect published version, minor changes to spelling and format
Published: 2009
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4. Characterization of the Millimeter-Wave Polarization of Centaurus A with QUaD

Author: Zemcov, M., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Friedman, R. B., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., O'Sullivan, C., Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., Taylor, A. N., Thompson, K. L., Turner, A. H., and Wu, E. Y. S.
Subjects: Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract: Centaurus (Cen) A represents one of the best candidates for an isolated, compact, highly polarized source that is bright at typical cosmic microwave background (CMB) experiment frequencies. We present measurements of the 4 degree by 2 degree region centered on Cen A with QUaD, a CMB polarimeter whose absolute polarization angle is known to 0.5 degrees. Simulations are performed to assess the effect of misestimation of the instrumental parameters on the final measurement and systematic errors due to the field's background structure and temporal variability from Cen A's nuclear region are determined. The total (Q, U) of the inner lobe region is (1.00 +/- 0.07 (stat.) +/- 0.04 (sys.), -1.72 +/- 0.06 +/- 0.05) Jy at 100 GHz and (0.80 +/- 0.06 +/- 0.06, -1.40 +/- 0.07 +/- 0.08) Jy at 150 GHz, leading to polarization angles and total errors of -30.0 +/- 1.1 degrees and -29.1 +/- 1.7 degrees. These measurements will allow the use of Cen A as a polarized calibration source for future millimeter experiments., Comment: 9 pages, 8 figures, v2 matches version published in ApJ
Published: 2009
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5. Improved measurements of the temperature and polarization of the CMB from QUaD

Author: The QUaD collaboration, Brown, M. L., Ade, P., Bock, J., Bowden, M., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Friedman, R. B., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., O'Sullivan, C., Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: Astrophysics - Cosmology and Extragalactic Astrophysics
Abstract: We present an improved analysis of the final dataset from the QUaD experiment. Using an improved technique to remove ground contamination, we double the effective sky area and hence increase the precision of our CMB power spectrum measurements by ~30% versus that previously reported. In addition, we have improved our modeling of the instrument beams and have reduced our absolute calibration uncertainty from 5% to 3.5% in temperature. The robustness of our results is confirmed through extensive jackknife tests and by way of the agreement we find between our two fully independent analysis pipelines. For the standard 6-parameter LCDM model, the addition of QUaD data marginally improves the constraints on a number of cosmological parameters over those obtained from the WMAP experiment alone. The impact of QUaD data is significantly greater for a model extended to include either a running in the scalar spectral index, or a possible tensor component, or both. Adding both the QUaD data and the results from the ACBAR experiment, the uncertainty in the spectral index running is reduced by ~25% compared to WMAP alone, while the upper limit on the tensor-to-scalar ratio is reduced from r < 0.48 to r < 0.33 (95% c.l). This is the strongest limit on tensors to date from the CMB alone. We also use our polarization measurements to place constraints on parity violating interactions to the surface of last scattering, constraining the energy scale of Lorentz violating interactions to < 1.5 x 10^{-43} GeV (68% c.l.). Finally, we place a robust upper limit on the strength of the lensing B-mode signal. Assuming a single flat band power between l = 200 and l = 2000, we constrain the amplitude of B-modes to be < 0.57 micro-K^2 (95% c.l.)., Comment: 23 pages, 19 figures, updated to reflect published version
Published: 2009
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6. Small Angular Scale Measurements of the CMB Temperature Power Spectrum from QUaD

Author: QUaD collaboration, Friedman, R. B., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Sullivan, C. O', Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: Astrophysics - Cosmology and Extragalactic Astrophysics
Abstract: We present measurements of the cosmic microwave background (CMB) radiation temperature anisotropy in the multipole range 2000
Published: 2009
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7. Cosmological Parameters from the QUaD CMB polarization experiment

Author: QUaD collaboration, Castro, P. G., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Church, S., Culverhouse, T., Friedman, R. B., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Pryke, C., Schwarz, R., O'Sullivan, C., Piccirillo, L., Rajguru, N., Rusholme, B., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: Astrophysics - Cosmology and Extragalactic Astrophysics
Abstract: In this paper we present a parameter estimation analysis of the polarization and temperature power spectra from the second and third season of observations with the QUaD experiment. QUaD has for the first time detected multiple acoustic peaks in the E-mode polarization spectrum with high significance. Although QUaD-only parameter constraints are not competitive with previous results for the standard 6-parameter LCDM cosmology, they do allow meaningful polarization-only parameter analyses for the first time. In a standard 6-parameter LCDM analysis we find the QUaD TT power spectrum to be in good agreement with previous results. However, the QUaD polarization data shows some tension with LCDM. The origin of this 1 to 2 sigma tension remains unclear, and may point to new physics, residual systematics or simple random chance. We also combine QUaD with the five-year WMAP data set and the SDSS Luminous Red Galaxies 4th data release power spectrum, and extend our analysis to constrain individual isocurvature mode fractions, constraining cold dark matter density, alpha(cdmi)<0.11 (95 % CL), neutrino density, alpha(ndi)<0.26 (95 % CL), and neutrino velocity, alpha(nvi)<0.23 (95 % CL), modes. Our analysis sets a benchmark for future polarization experiments., Comment: 8 pages, 5 figures, submitted to ApJ
Published: 2009
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8. Parity violation constraints using 2006-2007 QUaD CMB polarization spectra

Author: QUaD Collaboration, Wu, E. Y. S., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Friedman, R., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., O'Sullivan, C., Taylor, A. N., Thompson, K. L., Turner, A. H., and Zemcov, M.
Subjects: Astrophysics, High Energy Physics - Phenomenology
Abstract: We constrain parity-violating interactions to the surface of last scattering using spectra from the QUaD experiment's second and third seasons of observations by searching for a possible systematic rotation of the polarization directions of CMB photons. We measure the rotation angle due to such a possible "cosmological birefringence" to be 0.55 deg. +/- 0.82 deg. (random) +/- 0.5 deg. (systematic) using QUaD's 100 and 150 GHz TB and EB spectra over the multipole range 200 < l < 2000, consistent with null, and constrain Lorentz violating interactions to < 2^-43 GeV (68% confidence limit). This is the best constraint to date on electrodynamic parity violation on cosmological scales., Comment: 4 pages, 2 figures, accepted to Physical Review Letters. Improved method, updated result and clarified language
Published: 2008
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9. QUaD: A High-Resolution Cosmic Microwave Background Polarimeter

Author: QUaD collaboration, Hinderks, J. R., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Carlstrom, J. E., Castro, P. G., Church, S., Culverhouse, T., Friedman, R., Ganga, K., Gear, W. K., Gupta, S., Harris, J., Haynes, V., Keating, B. G., Kovac, J., Kirby, E., Lange, A. E., Leitch, E., Mallie, O. E., Melhuish, S., Memari, Y., Murphy, J. A., Orlando, A., Schwarz, R., O'Sullivan, C., Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Taylor, A. N., Thompson, K. L., Tucker, C., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: Astrophysics
Abstract: We describe the QUaD experiment, a millimeter-wavelength polarimeter designed to observe the Cosmic Microwave Background (CMB) from a site at the South Pole. The experiment comprises a 2.64 m Cassegrain telescope equipped with a cryogenically cooled receiver containing an array of 62 polarization-sensitive bolometers. The focal plane contains pixels at two different frequency bands, 100 GHz and 150 GHz, with angular resolutions of 5 arcmin and 3.5 arcmin, respectively. The high angular resolution allows observation of CMB temperature and polarization anisotropies over a wide range of scales. The instrument commenced operation in early 2005 and collected science data during three successive Austral winter seasons of observation., Comment: 23 pages, author list and text updated to reflect published version
Published: 2008
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10. Second and third season QUaD CMB temperature and polarization power spectra

Author: QUaD collaboration, Pryke, C., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Friedman, R., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Schwarz, R., O'Sullivan, C., Piccirillo, L., Rajguru, N., Rusholme, B., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: Astrophysics
Abstract: We report results from the second and third seasons of observation with the QUaD experiment. Angular power spectra of the Cosmic Microwave Background are derived for both temperature and polarization at both 100 GHz and 150 GHz, and as cross frequency spectra. All spectra are subjected to an extensive set of jackknife tests to probe for possible systematic contamination. For the implemented data cuts and processing technique such contamination is undetectable. We analyze the difference map formed between the 100 and 150 GHz bands and find no evidence of foreground contamination in polarization. The spectra are then combined to form a single set of results which are shown to be consistent with the prevailing LCDM model. The sensitivity of the polarization results is considerably better than that of any previous experiment -- for the first time multiple acoustic peaks are detected in the E-mode power spectrum at high significance., Comment: 24 pages, 23 figures, updated to reflect published version
Published: 2008
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11. 316P Comprehensive characterization of the HER2-enriched intrinsic molecular subtype in ER-positive HER2-negative breast cancer

Author: Hohmann, L., Sigurjónsdóttir, K., Bosch, A., Nacer, D.F., Veerla, S., Häkkinen, J., Vallon-Christersson, J., Borg, Å., Memari, Y., Davies, H., Nik-Zainal, S., and Staaf, J.
Published: 2023
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12. CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module

Author: Dougherty, G.W., Mizuno, K., Nöthe-Menchen, T., Ikawa, Y., Boldt, K., Ta-Shma, A., Aprea, I., Minegishi, K., Pang, Y.P., Pennekamp, P., Loges, N.T., Raidt, J., Hjeij, R., Wallmeier, J., Mussaffi, H., Perles, Z., Elpeleg, O., Rabert, F., Shiratori, H., Letteboer, S.J.F., Horn, N., Young, S., Strünker, T., Stumme, F., Werner, C., Olbrich, H., Takaoka, K., Ide, T., Twan, W.K., Biebach, L., Große-Onnebrink, J., Klinkenbusch, J.A., Praveen, K., Bracht, D.C., Höben, I.M., Junger, K., Gützlaff, J., Cindrić, S., Aviram, M., Kaiser, T., Memari, Y., Dzeja, P.P., Dworniczak, B., Ueffing, M., Roepman, R., Bartscherer, K., Katsanis, N., Davis, E.E., Amirav, I., Hamada, H., Omran, H., Dougherty, G.W., Mizuno, K., Nöthe-Menchen, T., Ikawa, Y., Boldt, K., Ta-Shma, A., Aprea, I., Minegishi, K., Pang, Y.P., Pennekamp, P., Loges, N.T., Raidt, J., Hjeij, R., Wallmeier, J., Mussaffi, H., Perles, Z., Elpeleg, O., Rabert, F., Shiratori, H., Letteboer, S.J.F., Horn, N., Young, S., Strünker, T., Stumme, F., Werner, C., Olbrich, H., Takaoka, K., Ide, T., Twan, W.K., Biebach, L., Große-Onnebrink, J., Klinkenbusch, J.A., Praveen, K., Bracht, D.C., Höben, I.M., Junger, K., Gützlaff, J., Cindrić, S., Aviram, M., Kaiser, T., Memari, Y., Dzeja, P.P., Dworniczak, B., Ueffing, M., Roepman, R., Bartscherer, K., Katsanis, N., Davis, E.E., Amirav, I., Hamada, H., and Omran, H.
Abstract: Contains fulltext : 229376.pdf (publisher's version ) (Open Access), Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45(-/-) mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module.
Published: 2020

13. Erratum to: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps (Nature Genetics, (2016), 48, 11, (1303-1312), 10.1038/ng.3668)

Author: Iotchkova, V., Huang, J., Morris, J. A., Jain, D., Barbieri, C., Ukovich, Walter, Min, J. L., Chen, L., Astle, W., Cocca, M., Deelen, P., Elding, H., Farmaki, A. -E., Franklin, C. S., Franberg, M., Gaunt, T. R., Hofman, A., Jiang, T., Kleber, M. E., Lachance, G., Luan, J., Malerba, G., Matchan, A., Mead, D., Memari, Y., Ntalla, I., Panoutsopoulou, K., Pazoki, R., Perry, J. R. B., Rivadeneira, F., Sabater-Lleal, M., Sennblad, B., Shin, S. -Y., Southam, L., Traglia, M., van Dijk, F., van Leeuwen, E. M., Zaza, G., Zhang, W., Amin, N., Butterworth, A., Chambers, J. C., Dedoussis, G., Dehghan, A., Franco, O. H., Franke, L., Frontini, M., Gambaro, G., Gasparini, P., Hamsten, A., Isaacs, A., Kooner, J. S., Kooperberg, C., Langenberg, C., Marz, W., Scott, R. A., Swertz, M. A., Toniolo, D., Uitterlinden, A. G., van Duijn, C. M., Watkins, H., Zeggini, E., Maurano, M. T., Timpson, N. J., Reiner, A. P., Auer, P. L., Soranzo, N., Iotchkova, V., Huang, J., Morris, J. A., Jain, D., Barbieri, C., Ukovich, Walter, Min, J. L., Chen, L., Astle, W., Cocca, M., Deelen, P., Elding, H., Farmaki, A. -E., Franklin, C. S., Franberg, M., Gaunt, T. R., Hofman, A., Jiang, T., Kleber, M. E., Lachance, G., Luan, J., Malerba, G., Matchan, A., Mead, D., Memari, Y., Ntalla, I., Panoutsopoulou, K., Pazoki, R., Perry, J. R. B., Rivadeneira, F., Sabater-Lleal, M., Sennblad, B., Shin, S. -Y., Southam, L., Traglia, M., van Dijk, F., van Leeuwen, E. M., Zaza, G., Zhang, W., Amin, N., Butterworth, A., Chambers, J. C., Dedoussis, G., Dehghan, A., Franco, O. H., Franke, L., Frontini, M., Gambaro, G., Gasparini, P., Hamsten, A., Isaacs, A., Kooner, J. S., Kooperberg, C., Langenberg, C., Marz, W., Scott, R. A., Swertz, M. A., Toniolo, D., Uitterlinden, A. G., van Duijn, C. M., Watkins, H., Zeggini, E., Maurano, M. T., Timpson, N. J., Reiner, A. P., Auer, P. L., and Soranzo, N.
Subjects: Author correction
Abstract: In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.
Published: 2018

14. A Simplified Approach for Prosthetic Rehabilitation of an Anophtalmic Patient with Chronic Mucoid Discharge Using a Previous Ocular Prosthesis

Author: Memari Y, Fayaz A, and Tadayonfard A
Subjects: lcsh:RK1-715, lcsh:R5-920, genetic structures, Maxillofacial Prosthesis, lcsh:Dentistry, Prosthetic Eye, Custom Ocular Prosthesis, sense organs, lcsh:Medicine (General), eye diseases, Impression
Abstract: The defects of eye, whatever the cause, are associated with significant anatomical deficiency and emotional and psychological disturbance for affected patients. Defect size may range from a small enucleation defect to an extensive exenterated one affecting eye and surrounding soft and hard tissues in maxillofacial complex. A properly fabricated custom ocular or orbital prosthesis could give the patient an optimal normalcy in social and psychological as well as functional aspects. A 68-year-old male patient presented with an enucleation defect in the left eye. After clinical examination, an impression was taken with additional silicon elastomeric impression material using patient’s previous prosthesis as a custom tray. Then, the scleral blank was made from wax and the Iris was attached to it. The external clear acrylic resin was packed and processed. The prosthesis was polished and delivered to patient. Modifying and converting a previously fabricated ocular prosthesis into a newly fabricated well-fitting custom ocular prosthesis can help minimizing clinical adjustments and simplifying laboratory procedures.
Published: 2017

15. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author: Haworth, S, Shapland, CY, Hayward, C, Prins, BP, Felix, JF, Medina-Gomez, C, Rivadeneira, F, Wang, C, Ahluwalia, TS, Vrijheid, M, Guxens, M, Sunyer, J, Tachmazidou, I, Walter, K, Iotchkova, V, Jackson, A, Cleal, L, Huffmann, J, Min, JL, Sass, L, Timmers, PRHJ, Al Turki, S, Anderson, CA, Anney, R, Antony, D, Artigas, MS, Ayub, M, Bala, S, Barrett, JC, Barroso, I, Beales, P, Bentham, J, Bhattacharya, S, Birney, E, Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G, Calissano, M, Carss, K, Charlton, R, Chatterjee, K, Chen, L, Ciampi, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, DA, Cosgrove, C, Cox, T, Craddock, N, Crooks, L, Curran, S, Curtis, D, Daly, A, Danecek, P, Day, INM, Day-Williams, A, Dominiczak, A, Down, T, Du, Y, Dunham, I, Durbin, R, Edkins, S, Ekong, R, Ellis, P, Evans, DM, Farooqi, IS, Fitzpatrick, DR, Flicek, P, Floyd, J, Foley, AR, Franklin, CS, Futema, M, Gallagher, L, Gaunt, TR, Geihs, M, Geschwind, D, Greenwood, CMT, Griffin, H, Grozeva, D, Guo, X, Gurling, H, Hart, D, Hendricks, AE, Holmans, P, Howie, B, Huang, J, Huang, L, Hubbard, T, Humphries, SE, Hurles, ME, Hysi, P, Jackson, DK, Jamshidi, Y, Joyce, C, Karczewski, KJ, Kaye, J, Keane, T, Kemp, JP, Kennedy, K, Kent, A, Keogh, J, Khawaja, F, van Kogelenberg, M, Kolb-Kokocinski, A, Lachance, G, Langford, C, Lawson, D, Lee, I, Lek, M, Li, R, Li, Y, Liang, J, Lin, H, Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M, MacArthur, DG, Mangino, M, Marchini, J, Marenne, G, Maslen, J, Mathieson, I, McCarthy, S, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Memari, Y, Metrustry, S, Migone, N, Mitchison, HM, Moayyeri, A, Morris, A, Morris, J, Muddyman, D, Muntoni, F, Northstone, K, O'Donovan, MC, O'Rahilly, S, Onoufriadis, A, Oualkacha, K, Owen, MJ, Palotie, A, Panoutsopoulou, K, Parker, V, Parr, JR, Paternoster, L, Paunio, T, Payne, F, Payne, SJ, Perry, JRB, Pietilainen, O, Plagnol, V, Pollitt, RC, Porteous, DJ, Povey, S, Quail, MA, Quaye, L, Raymond, FL, Rehnstrom, K, Richards, JB, Ridout, CK, Ring, S, Ritchie, GRS, Roberts, N, Robinson, RL, Savage, DB, Scambler, P, Schiffels, S, Schmidts, M, Schoenmakers, N, Scott, RH, Semple, RK, Serra, E, Sharp, SI, Shaw, A, Shihab, HA, Shin, S-Y, Skuse, D, Small, KS, Smee, C, Smith, BH, Soranzo, N, Southam, L, Spasic-Boskovic, O, Spector, TD, St Clair, D, Stalker, J, Stevens, E, Sun, J, Surdulescu, G, Suvisaari, J, Syrris, P, Taylor, R, Tian, J, Tobin, MD, Valdes, AM, Vandersteen, AM, Vijayarangakannan, P, Visscher, PM, Wain, LV, Walters, JTR, Wang, G, Wang, J, Wang, Y, Ward, K, Wheeler, E, Whyte, T, Williams, HJ, Williamson, KA, Wilson, C, Wilson, SG, Wong, K, Xu, C, Yang, J, Zhang, F, Zhang, P, Zheng, H-F, Smith, GD, Fisher, SE, Wilson, JF, Cole, TJ, Fernandez-Orth, D, Bonnelykke, K, Bisgaard, H, Pennell, CE, Jaddoe, VWV, Dedoussis, G, Timpson, N, Zeggini, E, Vitart, V, St Pourcain, B, UK10K Consortium, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, and Child and Adolescent Psychiatry / Psychology
Abstract: Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.
Published: 2019

16. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author: Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), Pourcain, B.S. (Beate), Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), and Pourcain, B.S. (Beate)
Abstract: Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for lowfrequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carrie
Published: 2019
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17. Homozygous loss-of-function variants in European cosmopolitan and isolate populations

Author: Kaiser, V.B., Svinti, V., Prendergast, J.G., Chau, Y.Y., Campbell, A., Patarcic, I., Barroso, I., Joshi, P.K., Hastie, N.D., Miljkovic, A., Taylor, M.S., Enroth, S., Memari, Y., Kolb-Kokocinski, A., Wright, A.F., Gyllensten, U., Durbin, R., Rudan, I., Campbell, H., Polašek, O., Johansson, A., Sauer, S., Porteous, D.J., Fraser, R.M., Drake, C., Vitart, V., Hayward, C., Semple, C.A., and Wilson, J.F.
Subjects: Phenotype, Gene Frequency, Homozygote, Mutation, Humans, Exome, Original Articles, Technology Platforms, Selection, Genetic, White People
Abstract: Homozygous Loss of Function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown - as are the phenotypic effects of losing function for most human genes. Here, we make use of 1,432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation.
Published: 2015
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18. Erratum to: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author: Iotchkova, V. (Valentina), Huang, J. (Jie), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimilian), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J., Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John R B), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A. (Adam), Chambers, J.C. (John C), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Isaacs, A.J. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A.P. (Alexander P), Auer, P.L. (Paul L), Soranzo, N. (Nicole), Iotchkova, V. (Valentina), Huang, J. (Jie), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimilian), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J., Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John R B), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A. (Adam), Chambers, J.C. (John C), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Isaacs, A.J. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A.P. (Alexander P), Auer, P.L. (Paul L), and Soranzo, N. (Nicole)
Abstract: In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.
Published: 2018
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19. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author: Hendricks, A.E. Bochukova, E.G. Marenne, G. Keogh, J.M. Atanassova, N. Bounds, R. Wheeler, E. Mistry, V. Henning, E. Körner, A. Muddyman, D. McCarthy, S. Hinney, A. Hebebrand, J. Scott, R.A. Langenberg, C. Wareham, N.J. Surendran, P. Howson, J.M. Butterworth, A.S. Danesh, J. Nordestgaard, Bø.G. Nielsen, S.F. Afzal, S. Papadia, S. Ashford, S. Garg, S. Millhauser, G.L. Palomino, R.I. Kwasniewska, A. Tachmazidou, I. O'Rahilly, S. Zeggini, E. Barroso, I. Farooqi, I.S. Benzeval, M. Burton, J. Buck, N. Jäckle, A. Kumari, M. Laurie, H. Lynn, P. Pudney, S. Rabe, B. Wolke, D. Overvad, K. Tjønneland, A. Clavel-Chapelon, F. Kaaks, R. Boeing, H. Trichopoulou, A. Ferrari, P. Palli, D. Krogha, V. Panico, S. Tuminoa, R. Matullo, G. Boer, J. Van Der Schouw, Y. Weiderpass, E. Quiros, J.R. Sánchez, M.-J. Navarro, C. Moreno-Iribas, C. Arriola, L. Melander, O. Wennberg, P. Key, T.J. Riboli, E. Turki, S.A. Anderson, C.A. Anney, R. Antony, D. Soler Artigas, M. Ayub, M. Bala, S. Barrett, J.C. Beales, P. Bentham, J. Bhattacharyaa, S. Birney, E. Blackwooda, D. Bobrow, M. Bolton, P.F. Boustred, C. Breen, G. Calissanoa, M. Carss, K. Charlton, R. Chatterjee, K. Chen, L. Ciampia, A. Cirak, S. Clapham, P. Clement, G. Coates, G. Coccaa, M. Collier, D.A. Cosgrove, C. Coxa, T. Craddock, N. Crooks, L. Curran, S. Curtis, D. Daly, A. Danecek, P. Day, I.N.M. Day-Williams, A. Dominiczak, A. Down, T. Du, Y. Dunham, I. Durbin, R. Edkins, S. Ekong, R. Ellis, P. Evansa, D.M. Fitzpatrick, D.R. Flicek, P. Floyd, J. Foley, A.R. Franklin, C.S. Futema, M. Gallagher, L. Gaunt, T.R. Geihs, M. Geschwind, D. Greenwood, C.M.T. Griffin, H. Grozeva, D. Guo, X. Guo, X. Gurling, H. Hart, D. Holmans, P. Howie, B. Huang, J. Huang, L. Hubbard, T. Humphries, S.E. Hurles, M.E. Hysi, P. Iotchkova, V. Jackson, D.K. Jamshidi, Y. Joyce, C. Karczewski, K.J. Kaye, J. Keane, T. Kemp, J.P. Kennedy, K. Kent, A. Khawaja, F. Van Kogelenberg, M. Kolb-Kokocinski, A. Lachance, G. Langford, C. Lawson, D. Lee, I. Lek, M. Li, R. Li, Y. Liang, J. Lin, H. Liu, R. Lönnqvist, J. Lopes, L.R. Lopes, M. MacArthur, D.G. Mangino, M. Marchini, J. Maslen, J. Mathieson, I. McGuffin, P. McIntosh, A.M. McKechanie, A.G. McQuillin, A. Memari, Y. Metrustry, S. Migone, N. Min, J.L. Mitchison, H.M. Moayyeri, A. Morris, A. Morris, J. Muntoni, F. Northstone, K. O'Donovan, M.C. Onoufriadis, A. Oualkacha, K. Owen, M.J. Palotie, A. Panoutsopoulou, K. Parker, V. Parr, J.R. Paternoster, L. Paunio, T. Payne, F. Payne, S.J. Perry, J.R.B. Pietilainen, O. Plagnol, V. Pollitt, R.C. Porteous, D.J. Povey, S. Quail, M.A. Quaye, L. Raymond, F.L. Rehnström, K. Richards, J.B. Ridout, C.K. Ring, S. Ritchie, G.R.S. Roberts, N. Robinson, R.L. Savage, D.B. Scambler, P. Schiffels, S. Schmidts, M. Schoenmakers, N. Scott, R.H. Semple, R.K. Serra, E. Sharp, S.I. Shaw, A. Shihab, H.A. Shin, S.-Y. Skuse, D. Small, K.S. Smee, C. Smith, B.H. Davey Smith, G. Soranzo, N. Southam, L. Spasic-Boskovic, O. Spector, T.D. St Clair, D. St Pourcain, B. Stalker, J. Stevens, E. Sun, J. Surdulescu, G. Suvisaari, J. Syrris, P. Taylor, R. Tian, J. Timpson, N.J. Tobin, M.D. Valdes, A.M. Vandersteen, A.M. Vijayarangakannan, P. Visscher, P.M. Wain, L.V. Walter, K. Walters, J.T.R. Wang, G. Wang, J. Wang, Y. Ward, K. Whyte, T. Williams, H.J. Williamson, K.A. Wilson, C. Wilson, S.G. Wong, K. Xu, C. Yang, J. Zhang, F. Zhang, P. Zheng, H.-F.
Abstract: Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies. © 2017 The Author(s).
Published: 2017

20. Common genetic variation drives molecular heterogeneity in human iPSCs

Author: Kilpinen, H, Goncalves, A, Leha, A, Afzal, V, Alasoo, K, Ashford, S, Bala, S, Bensaddek, D, Casale, FP, Ulley, OJC, Danecek, P, Faulconbridge, A, Harrison, PW, Kathuria, A, McCarthy, D, McCarthy, SA, Meleckyte, R, Memari, Y, Moens, N, Soares, F, Mann, A, Streeter, I, Agu, CA, Alderton, A, Nelson, R, Harper, S, Patel, M, White, A, Patel, SR, Clarke, L, Halai, R, Kirton, CM, Kolb-Kokocinski, A, Beales, P, Birney, E, Danovi, D, Lamond, AI, Ouwehand, WH, Vallier, L, Watt, FM, Durbin, R, Stegle, O, Gaffney, DJ, Kilpinen, H, Goncalves, A, Leha, A, Afzal, V, Alasoo, K, Ashford, S, Bala, S, Bensaddek, D, Casale, FP, Ulley, OJC, Danecek, P, Faulconbridge, A, Harrison, PW, Kathuria, A, McCarthy, D, McCarthy, SA, Meleckyte, R, Memari, Y, Moens, N, Soares, F, Mann, A, Streeter, I, Agu, CA, Alderton, A, Nelson, R, Harper, S, Patel, M, White, A, Patel, SR, Clarke, L, Halai, R, Kirton, CM, Kolb-Kokocinski, A, Beales, P, Birney, E, Danovi, D, Lamond, AI, Ouwehand, WH, Vallier, L, Watt, FM, Durbin, R, Stegle, O, and Gaffney, DJ
Abstract: Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.
Published: 2017

21. Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

Author: Tachmazidou, I, Suveges, D, Min, JL, Ritchie, GRS, Steinberg, J, Walter, K, Iotchkova, V, Schwartzentruber, J, Huang, J, Memari, Y, McCarthy, S, Crawford, AA, Bombieri, C, Cocca, M, Farmaki, AE, Gaunt, TR, Jousilahti, P, Kooijman, Marjolein, Lehne, B, Malerba, G, Mannisto, S, Matchan, A, Medina Gomez, Maria, Metrustry, SJ, Nag, A, Ntalla, I, Paternoster, L, Rayner, NW, Sala, C, Scott, WR, Shihab, HA, Southam, L, St Pourcain, B, Traglia, M, Trajanoska, Katerina, Zaza, G, Zhang, WH, Artigas, MS, Bansal, N, Benn, M, Chen, ZS, Danecek, P, Lin, WY, Locke, A, Luan, JA, Manning, AK, Mulas, A, Sidore, C, Tybjaerg-Hansen, A, Varbo, A, Zoledziewska, M, Finan, C, Hatzikotoulas, K, Hendricks, AE, Kemp, JP, Moayyeri, A, Panoutsopoulou, K, Szpak, M, Wilson, SG, Boehnke, M, Cucca, F, Di Angelantonio, E, Langenberg, C, Lindgren, C, McCarthy, MI, Morris, AP, Nordestgaard, BG, Scott, RA, Tobin, MD, Wareham, NJ, Burton, P, Chambers, JC, Smith, GD, Dedoussis, G, Felix, Janine, Franco Duran, OH, Gambaro, G, Gasparini, P, Hammond, CJ, Hofman, Bert, Jaddoe, Vincent, Kleber, M, Kooner, JS, Perola, M, Relton, C, Ring, SM, Rivadeneira, Fernando, Salomaa, V, Spector, TD, Stegle, O, Toniolo, D, Uitterlinden, André, Barroso, I, Greenwood, CMT, Perry, JRB, Walker, BR, Butterworth, AS, Xue, YL, Durbin, R, Small, KS, Soranzo, N, Timpson, NJ, Zeggini, E, Tachmazidou, I, Suveges, D, Min, JL, Ritchie, GRS, Steinberg, J, Walter, K, Iotchkova, V, Schwartzentruber, J, Huang, J, Memari, Y, McCarthy, S, Crawford, AA, Bombieri, C, Cocca, M, Farmaki, AE, Gaunt, TR, Jousilahti, P, Kooijman, Marjolein, Lehne, B, Malerba, G, Mannisto, S, Matchan, A, Medina Gomez, Maria, Metrustry, SJ, Nag, A, Ntalla, I, Paternoster, L, Rayner, NW, Sala, C, Scott, WR, Shihab, HA, Southam, L, St Pourcain, B, Traglia, M, Trajanoska, Katerina, Zaza, G, Zhang, WH, Artigas, MS, Bansal, N, Benn, M, Chen, ZS, Danecek, P, Lin, WY, Locke, A, Luan, JA, Manning, AK, Mulas, A, Sidore, C, Tybjaerg-Hansen, A, Varbo, A, Zoledziewska, M, Finan, C, Hatzikotoulas, K, Hendricks, AE, Kemp, JP, Moayyeri, A, Panoutsopoulou, K, Szpak, M, Wilson, SG, Boehnke, M, Cucca, F, Di Angelantonio, E, Langenberg, C, Lindgren, C, McCarthy, MI, Morris, AP, Nordestgaard, BG, Scott, RA, Tobin, MD, Wareham, NJ, Burton, P, Chambers, JC, Smith, GD, Dedoussis, G, Felix, Janine, Franco Duran, OH, Gambaro, G, Gasparini, P, Hammond, CJ, Hofman, Bert, Jaddoe, Vincent, Kleber, M, Kooner, JS, Perola, M, Relton, C, Ring, SM, Rivadeneira, Fernando, Salomaa, V, Spector, TD, Stegle, O, Toniolo, D, Uitterlinden, André, Barroso, I, Greenwood, CMT, Perry, JRB, Walker, BR, Butterworth, AS, Xue, YL, Durbin, R, Small, KS, Soranzo, N, Timpson, NJ, and Zeggini, E
Published: 2017

22. A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site

Author: Nürnberg ST, Rendon A, Smethurst PA, Paul DS, Voss K, Thon JN, Lloyd Jones H, Sambrook JG, Tijssen MR, Gieger C, Radhakrishnan A, Cvejic A, Tang W, Porcu E, Pistis G, Serbanovic Canic J, Elling U, Goodall AH, Labrune Y, Lopez LM, Mägi R, Meacham S, Okada Y, Sorice R, Teumer A, Zhang W, Ramirez Solis R, Bis JC, Ellinghaus D, Gögele M, Hottenga JJ, Langenberg C, Kovacs P, F. P, Shin SY, Esko T, Hartiala J, Kanoni S, Murgia F, Parsa A, Stephens J, van der Harst P, van der Schoot C, Allayee H, Attwood A, Balkau B, Bastardot F, Basu S, Baumeister SE, Biino G, Bomba L, Bonnefond A, Cambien F, Chambers JC, Cucca F, Davies G, de Geus EJ, de Boer RA, Döring A, Elliott P, Erdmann J, Feng W, Evans DM, Falchi M, Folsom AR, Frazer IH, Gibson QD, Glazer NL, Hammond C, Hartikainen AL, Heckbert SR, Hengstenberg C, Hersch M, Illig T, Loos RJ, Jolley J, Khaw KT, Kühnel B, Kyrtsonis MC, Lagou V, Lumley T, Mangino M, Maschio A, Mateo Leach I, McKnight B, Memari Y, Mitchell BD, Montgomery GW, Nöthlings U, Nakamura Y, Nauck M, Navis G, Nolte IM, Porteous DJ, Pouta A, Pramstaller PP, Pullat J, Ring SM, Rotter JI, Ruggiero D, Ruokonen A, Sala C, Samani NJ, Sambrook J, Schlessinger D, Schreiber S, Schunkert H, Scott J, Smith NL, Snieder H, Starr JM, Stumvoll M, Takahashi A, Taylor K, Tenesa A, Thein SL, Tönjes A, Uda M, Ulivi S, Wichmann HE, Yang TP, van Veldhuisen DJ, Visscher PM, Völker U, Wiggins KL, Willemsen G, Zhao JH, Zitting P, Bradley JR, Dedoussis GV, Hazen SL, Metspalu A, Pirastu M, Shuldiner AR, van Pelt L, Zwaginga JJ, Boomsma DI, Deary IJ, Franke A, Froguel P, Ganesh SK, Jarvelin MR, Martin NG, Meisinger C, Psaty BM, Spector TD, Wareham NJ, Akkerman JW, Ciullo M, Deloukas P, Greinacher A, Jupe S, Kamatani N, Khadake J, Kooner JS, Penninger J, Prokopenko I, Stemple D, Toniolo D, Wernisch L, Sanna S, Hicks AA, Ferreira MA, Italiano JE Jr, Gottgens B, Soranzo N, Ouwehand WH, PIRASTU, Nicola, D'ADAMO, ADAMO PIO, GASPARINI, PAOLO, Nürnberg, St, Rendon, A, Smethurst, Pa, Paul, D, Voss, K, Thon, Jn, Lloyd Jones, H, Sambrook, Jg, Tijssen, Mr, Gieger, C, Radhakrishnan, A, Cvejic, A, Tang, W, Porcu, E, Pistis, G, Serbanovic Canic, J, Elling, U, Goodall, Ah, Labrune, Y, Lopez, Lm, Mägi, R, Meacham, S, Okada, Y, Pirastu, Nicola, Sorice, R, Teumer, A, Zhang, W, Ramirez Solis, R, Bis, Jc, Ellinghaus, D, Gögele, M, Hottenga, Jj, Langenberg, C, Kovacs, P, F., P, Shin, Sy, Esko, T, Hartiala, J, Kanoni, S, Murgia, F, Parsa, A, Stephens, J, van der Harst, P, van der Schoot, C, Allayee, H, Attwood, A, Balkau, B, Bastardot, F, Basu, S, Baumeister, Se, Biino, G, Bomba, L, Bonnefond, A, Cambien, F, Chambers, Jc, Cucca, F, D'Adamo, ADAMO PIO, Davies, G, de Geus, Ej, de Boer, Ra, Döring, A, Elliott, P, Erdmann, J, Feng, W, Evans, Dm, Falchi, M, Folsom, Ar, Frazer, Ih, Gibson, Qd, Glazer, Nl, Hammond, C, Hartikainen, Al, Heckbert, Sr, Hengstenberg, C, Hersch, M, Illig, T, Loos, Rj, Jolley, J, Khaw, Kt, Kühnel, B, Kyrtsonis, Mc, Lagou, V, Lumley, T, Mangino, M, Maschio, A, Mateo Leach, I, Mcknight, B, Memari, Y, Mitchell, Bd, Montgomery, Gw, Nöthlings, U, Nakamura, Y, Nauck, M, Navis, G, Nolte, Im, Porteous, Dj, Pouta, A, Pramstaller, Pp, Pullat, J, Ring, Sm, Rotter, Ji, Ruggiero, D, Ruokonen, A, Sala, C, Samani, Nj, Sambrook, J, Schlessinger, D, Schreiber, S, Schunkert, H, Scott, J, Smith, Nl, Snieder, H, Starr, Jm, Stumvoll, M, Takahashi, A, Taylor, K, Tenesa, A, Thein, Sl, Tönjes, A, Uda, M, Ulivi, S, Wichmann, He, Yang, Tp, van Veldhuisen, Dj, Visscher, Pm, Völker, U, Wiggins, Kl, Willemsen, G, Zhao, Jh, Zitting, P, Bradley, Jr, Dedoussis, Gv, Gasparini, Paolo, Hazen, Sl, Metspalu, A, Pirastu, M, Shuldiner, Ar, van Pelt, L, Zwaginga, Jj, Boomsma, Di, Deary, Ij, Franke, A, Froguel, P, Ganesh, Sk, Jarvelin, Mr, Martin, Ng, Meisinger, C, Psaty, Bm, Spector, Td, Wareham, Nj, Akkerman, Jw, Ciullo, M, Deloukas, P, Greinacher, A, Jupe, S, Kamatani, N, Khadake, J, Kooner, J, Penninger, J, Prokopenko, I, Stemple, D, Toniolo, D, Wernisch, L, Sanna, S, Hicks, Aa, Ferreira, Ma, Italiano JE, Jr, Gottgens, B, Soranzo, N, Ouwehand, Wh, Biological Psychology, and EMGO+ - Mental Health
Subjects: Netherlands Twin Register (NTR), Transcription, Genetic, Gene Expression, Biochemistry, megakaryocyte, Mice, DNM3 promoter, Transcription (biology), GWAS, Platelet, Thrombopoiesis, Myeloid Ecotropic Viral Integration Site 1 Protein, Promoter Regions, Genetic, Cells, Cultured, Reverse Transcriptase Polymerase Chain Reaction, Hematology, Neoplasm Proteins, Haematopoiesis, Transcription Initiation Site, Megakaryocytes, platelet volume, DNM3, megakaryocytes, MEIS1, Blood Platelets, Chromatin Immunoprecipitation, Immunology, Biology, Polymorphism, Single Nucleotide, MEIS1 binding site, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Animals, Humans, Cell Lineage, Binding site, Gene, Transcription factor, Homeodomain Proteins, Binding Sites, Genome, Human, Platelet Count, Hydrazones, Genetic Variation, Cell Biology, Sequence Analysis, DNA, Platelets and Thrombopoiesis, Molecular biology, Dynamin III
Abstract: We recently identified 68 genomic loci where common sequence variants are associated with platelet count and volume. Platelets are formed in the bone marrow by megakaryocytes, which are derived from hematopoietic stem cells by a process mainly controlled by transcription factors. The homeobox transcription factor MEIS1 is uniquely transcribed in megakaryocytes and not in the other lineage-committed blood cells. By ChIP-seq, we show that 5 of the 68 loci pinpoint a MEIS1 binding event within a group of 252 MK-overexpressed genes. In one such locus in DNM3, regulating platelet volume, the MEIS1 binding site falls within a region acting as an alternative promoter that is solely used in megakaryocytes, where allelic variation dictates different levels of a shorter transcript. The importance of dynamin activity to the latter stages of thrombopoiesis was confirmed by the observation that the inhibitor Dynasore reduced murine proplatelet for-mation in vitro.
Published: 2013
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23. Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author: Iotchkova, V. (Valentina), Huang, J. (Jian), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimiliano), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J. (Jian'An), Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A.S. (Adam), Chambers, J.C. (John), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Issacs, A. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A. (Alexander), Auer, P. (Paul), Soranzo, N. (Nicole), Iotchkova, V. (Valentina), Huang, J. (Jian), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimiliano), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J. (Jian'An), Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A.S. (Adam), Chambers, J.C. (John), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Issacs, A. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A. (Alexander), Auer, P. (Paul), and Soranzo, N. (Nicole)
Abstract: Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low-frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.
Published: 2016
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24. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel.

Author: Huang, J., Howie, B., McCarthy, S., Memari, Y., Walter, K., Min, J.L., Danecek, P., Malerba, G., Trabetti, E., Zheng, H.F., Gambaro, G., Richards, J.B., Durbin, R., Timpson, N.J., Marchini, J., Soranzo, N., Schmidts, M., et al., Huang, J., Howie, B., McCarthy, S., Memari, Y., Walter, K., Min, J.L., Danecek, P., Malerba, G., Trabetti, E., Zheng, H.F., Gambaro, G., Richards, J.B., Durbin, R., Timpson, N.J., Marchini, J., Soranzo, N., Schmidts, M., and et al.
Abstract: Contains fulltext : 153109.pdf (publisher's version ) (Open Access), Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants.
Published: 2015

25. Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement

Author: Haack, T.B., Jackson, C.B., Murayama, K., Kremer, L.S., Schaller, A., Kotzaeridou, U., Vries, M.C. de, Schottmann, G., Santra, S., Büchner, B., Wieland, T., Graf, E., Freisinger, P., Eggimann, S., Ohtake, A., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Sauer, S., Memari, Y., Kolb-Kokocinski, A., Durbin, R., Hasselmann, O., Cremer, K., Albrecht, B., Wieczorek, D., Engels, H., Hahn, D., Zink, A.M., Alston, C.L., Taylor, R.W., Rodenburg, R.J., Trollmann, R., Sperl, W., Strom, T.M., Hoffmann, G.F., Mayr, J.A., Meitinger, T., Bolognini, R., Schuelke, M., Nuoffer, J.M., Kölker, S., Prokisch, H., Klopstock, T., Haack, T.B., Jackson, C.B., Murayama, K., Kremer, L.S., Schaller, A., Kotzaeridou, U., Vries, M.C. de, Schottmann, G., Santra, S., Büchner, B., Wieland, T., Graf, E., Freisinger, P., Eggimann, S., Ohtake, A., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Sauer, S., Memari, Y., Kolb-Kokocinski, A., Durbin, R., Hasselmann, O., Cremer, K., Albrecht, B., Wieczorek, D., Engels, H., Hahn, D., Zink, A.M., Alston, C.L., Taylor, R.W., Rodenburg, R.J., Trollmann, R., Sperl, W., Strom, T.M., Hoffmann, G.F., Mayr, J.A., Meitinger, T., Bolognini, R., Schuelke, M., Nuoffer, J.M., Kölker, S., Prokisch, H., and Klopstock, T.
Abstract: Contains fulltext : 154949.pdf (publisher's version ) (Open Access)
Published: 2015

26. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

Author: Zheng, H.-F. (Hou-Feng), Forgetta, V. (Vincenzo), Hsu, Y.-H. (Yi-Hsiang), Estrada Gil, K. (Karol), Rosello-Diez, A. (Alberto), Leo, P.J. (Paul), Dahia, C.L. (Chitra L.), Park-Min, K.H. (Kyung Hyun), Tobias, J.H. (Jon), Kooperberg, C. (Charles), Kleinman, A. (Aaron), Styrkarsdottir, U. (Unnur), Liu, C.-T. (Ching-Ti), Uggla, C. (Charlotta), Evans, D.S. (Daniel), Nielson, C. (Carrie), Walter, K. (Klaudia), Pettersson-Kymmer, U. (Ulrika), McCarthy, S. (Shane), Eriksson, J. (Joel), Kwan, T. (Tony), Jhamai, M. (Mila), Trajanoska, K. (Katerina), Memari, Y. (Yasin), Min, J.L. (Josine L.), Huang, J. (Jie), Danecek, P. (Petr), Wilmot, B. (Beth), Li, R. (Rui), Chou, W.-C. (Wen-Chi), Mokry, L.E. (Lauren E.), Moayyeri, A. (Alireza), Claussnitzer, M. (Melina), Cheng, C.-H. (Chia-Ho), Cheung, W. (Warren), Medina-Gomez, M.C. (Carolina), Ge, B. (Bing), Chen, S.-H. (Shu-Huang), Choi, K. (Kunho), Oei, L. (Ling), Fraser, J. (James), Kraaij, R. (Robert), Hibbs, M.A. (Matthew A.), Gregson, C.L. (Celia L.), Paquette, D. (Denis), Hofman, A. (Albert), Wibom, C. (Carl), Tranah, G.J. (Gregory), Marshall, M. (Mhairi), Gardiner, B.B. (Brooke B.), Cremin, K. (Katie), Auer, P. (Paul), Hsu, L. (Li), Ring, S. (Susan), Tung, J.Y. (Joyce Y.), Thorleifsson, G. (Gudmar), Enneman, A.W. (Anke), Schoor, N.M. (Natasja) van, Groot, L.C.P.G.M. (Lisette) de, Velde, N. (Nathalie) van der, Melin, B. (Beatrice), Kemp, J.P. (John), Christiansen, C., Sayers, I. (Ian), Zhou, Y. (Yanhua), Calderari, S. (Sophie), Rooij, J.G.J. (Jeroen) van, Carlson, C. (Chris), Peters, U. (Ulrike), Berlivet, S. (Soizik), Dostie, J. (Josée), Uitterlinden, A.G. (André), Williams, S.R. (Stephen R.), Farber, C. (Charles), Grinberg, D. (Daniel), LaCroix, A.Z. (Andrea), Haessler, J. (Jeff), Chasman, D.I. (Daniel), Giulianini, F. (Franco), Rose, L.M. (Lynda M.), Ridker, P.M. (Paul), Eisman, J.A. (John), Nguyen, T.V. (Tuan), Center, J.R. (Jacqueline), Nogues, X. (Xavier), Garcia-Giralt, N. (Natàlia), Launer, L.J. (Lenore), Gudnason, V. (Vilmunder), Mellström, D. (Dan), Vandenput, L. (Liesbeth), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Karlsson, M. (Magnus), Ljunggren, O. (Östen), Svensson, O. (Olle), Hallmans, G. (Göran), Rousseau, M.F. (Francois), Giroux, S. (Sylvie), Bussière, J. (Johanne), Arp, P.P. (Pascal), Koromani, F. (Fjorda), Prince, R.L. (Richard L.), Lewis, J.R. (Joshua), Langdahl, B.L. (Bente), Hermann, A.P. (A. Pernille), Jensen, J.-E.B. (Jens-Erik B.), Kaptoge, S. (Stephen), Khaw, K.T., Reeve, J. (Jonathan), Formosa, M.M. (Melissa M.), Xuereb-Anastasi, A. (Angela), Åkesson, K. (Kristina), McGuigan, F.E., Garg, G. (Gaurav), Olmos, D. (David), Zarrabeitia, M.T. (María), Riancho, J.A. (José), Ralston, S.H. (Stuart), Alonso, N. (Nerea), Jiang, X. (Xi), Goltzman, D. (David), Pastinen, T. (Tomi), Grundberg, E. (Elin), Gauguier, D. (Dominique), Orwoll, E.S. (Eric), Karasik, D. (David), Smith, A.V. (Davey), Siggeirsdottir, K. (Kristin), Harris, T.B. (Tamara), Zillikens, M.C. (Carola), Meurs, J.B.J. (Joyce) van, Thorsteinsdottir, U. (Unnur), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Soranzo, N. (Nicole), Durbin, R. (Richard), Wilson, S.G. (Scott), Ntzani, E.E. (Evangelia), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Hinds, D.A. (David A.), Spector, T.D. (Timothy), Cupples, L.A. (Adrienne), Ohlsson, C. (Claes), Greenwood, C.M.T. (Celia), Jackson, R.D. (Rebecca), Rowe, D.W. (David W.), Loomis, C.A. (Cynthia A.), Evans, D.M. (David M.), Ackert-Bicknell, C.L. (Cheryl), Joyner, A.L. (Alexandra L.), Duncan, E.L. (Emma), Kiel, D.P. (Douglas P.), Rivadeneira Ramirez, F. (Fernando), Richards, J.B. (Brent), Zheng, H.-F. (Hou-Feng), Forgetta, V. (Vincenzo), Hsu, Y.-H. (Yi-Hsiang), Estrada Gil, K. (Karol), Rosello-Diez, A. (Alberto), Leo, P.J. (Paul), Dahia, C.L. (Chitra L.), Park-Min, K.H. (Kyung Hyun), Tobias, J.H. (Jon), Kooperberg, C. (Charles), Kleinman, A. (Aaron), Styrkarsdottir, U. (Unnur), Liu, C.-T. (Ching-Ti), Uggla, C. (Charlotta), Evans, D.S. (Daniel), Nielson, C. (Carrie), Walter, K. (Klaudia), Pettersson-Kymmer, U. (Ulrika), McCarthy, S. (Shane), Eriksson, J. (Joel), Kwan, T. (Tony), Jhamai, M. (Mila), Trajanoska, K. (Katerina), Memari, Y. (Yasin), Min, J.L. (Josine L.), Huang, J. (Jie), Danecek, P. (Petr), Wilmot, B. (Beth), Li, R. (Rui), Chou, W.-C. (Wen-Chi), Mokry, L.E. (Lauren E.), Moayyeri, A. (Alireza), Claussnitzer, M. (Melina), Cheng, C.-H. (Chia-Ho), Cheung, W. (Warren), Medina-Gomez, M.C. (Carolina), Ge, B. (Bing), Chen, S.-H. (Shu-Huang), Choi, K. (Kunho), Oei, L. (Ling), Fraser, J. (James), Kraaij, R. (Robert), Hibbs, M.A. (Matthew A.), Gregson, C.L. (Celia L.), Paquette, D. (Denis), Hofman, A. (Albert), Wibom, C. (Carl), Tranah, G.J. (Gregory), Marshall, M. (Mhairi), Gardiner, B.B. (Brooke B.), Cremin, K. (Katie), Auer, P. (Paul), Hsu, L. (Li), Ring, S. (Susan), Tung, J.Y. (Joyce Y.), Thorleifsson, G. (Gudmar), Enneman, A.W. (Anke), Schoor, N.M. (Natasja) van, Groot, L.C.P.G.M. (Lisette) de, Velde, N. (Nathalie) van der, Melin, B. (Beatrice), Kemp, J.P. (John), Christiansen, C., Sayers, I. (Ian), Zhou, Y. (Yanhua), Calderari, S. (Sophie), Rooij, J.G.J. (Jeroen) van, Carlson, C. (Chris), Peters, U. (Ulrike), Berlivet, S. (Soizik), Dostie, J. (Josée), Uitterlinden, A.G. (André), Williams, S.R. (Stephen R.), Farber, C. (Charles), Grinberg, D. (Daniel), LaCroix, A.Z. (Andrea), Haessler, J. (Jeff), Chasman, D.I. (Daniel), Giulianini, F. (Franco), Rose, L.M. (Lynda M.), Ridker, P.M. (Paul), Eisman, J.A. (John), Nguyen, T.V. (Tuan), Center, J.R. (Jacqueline), Nogues, X. (Xavier), Garcia-Giralt, N. (Natàlia), Launer, L.J. (Lenore), Gudnason, V. (Vilmunder), Mellström, D. (Dan), Vandenput, L. (Liesbeth), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Karlsson, M. (Magnus), Ljunggren, O. (Östen), Svensson, O. (Olle), Hallmans, G. (Göran), Rousseau, M.F. (Francois), Giroux, S. (Sylvie), Bussière, J. (Johanne), Arp, P.P. (Pascal), Koromani, F. (Fjorda), Prince, R.L. (Richard L.), Lewis, J.R. (Joshua), Langdahl, B.L. (Bente), Hermann, A.P. (A. Pernille), Jensen, J.-E.B. (Jens-Erik B.), Kaptoge, S. (Stephen), Khaw, K.T., Reeve, J. (Jonathan), Formosa, M.M. (Melissa M.), Xuereb-Anastasi, A. (Angela), Åkesson, K. (Kristina), McGuigan, F.E., Garg, G. (Gaurav), Olmos, D. (David), Zarrabeitia, M.T. (María), Riancho, J.A. (José), Ralston, S.H. (Stuart), Alonso, N. (Nerea), Jiang, X. (Xi), Goltzman, D. (David), Pastinen, T. (Tomi), Grundberg, E. (Elin), Gauguier, D. (Dominique), Orwoll, E.S. (Eric), Karasik, D. (David), Smith, A.V. (Davey), Siggeirsdottir, K. (Kristin), Harris, T.B. (Tamara), Zillikens, M.C. (Carola), Meurs, J.B.J. (Joyce) van, Thorsteinsdottir, U. (Unnur), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Soranzo, N. (Nicole), Durbin, R. (Richard), Wilson, S.G. (Scott), Ntzani, E.E. (Evangelia), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Hinds, D.A. (David A.), Spector, T.D. (Timothy), Cupples, L.A. (Adrienne), Ohlsson, C. (Claes), Greenwood, C.M.T. (Celia), Jackson, R.D. (Rebecca), Rowe, D.W. (David W.), Loomis, C.A. (Cynthia A.), Evans, D.M. (David M.), Ackert-Bicknell, C.L. (Cheryl), Joyner, A.L. (Alexandra L.), Duncan, E.L. (Emma), Kiel, D.P. (Douglas P.), Rivadeneira Ramirez, F. (Fernando), and Richards, J.B. (Brent)
Abstract: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10-14), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10-11; ncases = 98,742 and n controls = 409,511). Using an En1 cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10-11). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation
Published: 2015
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27. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Author: Huang, J. (Jie), Howie, B. (Bryan), McCarthy, S. (Shane), Memari, Y. (Yasin), Walter, K. (Klaudia), Min, J.L. (Josine L.), Danecek, P. (Petr), Malerba, G. (Giovanni), Trabetti, E. (Elisabetta), Zheng, H.-F. (Hou-Feng), Gambaro, G. (Giovanni), Richards, J.B. (Brent), Durbin, R. (Richard), Timpson, N.J. (Nicholas), Marchini, J. (Jonathan), Soranzo, N. (Nicole), Al Turki, S.H. (Saeed), Amuzu, A. (Antoinette), Anderson, C. (Carl), Anney, R. (Richard), Antony, D. (Dinu), Artigas, M.S., Ayub, M. (Muhammad), Bala, S. (Senduran), Barrett, J.C. (Jeffrey), Barroso, I.E. (Inês), Beales, P.L. (Philip), Benn, M. (Marianne), Bentham, J. (Jamie), Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D.H.R. (Douglas), Bobrow, M. (Martin), Bochukova, E. (Elena), Bolton, P.F. (Patrick F.), Bounds, R. (Rebecca), Boustred, C. (Chris), Breen, G. (Gerome), Calissano, M. (Mattia), Carss, K. (Keren), Casas, J.P. (Juan Pablo), Chambers, J.C. (John C.), Charlton, R. (Ruth), Chatterjee, K. (Krishna), Chen, L. (Lu), Ciampi, A. (Antonio), Cirak, S. (Sebahattin), Clapham, P. (Peter), Clement, G. (Gail), Coates, G. (Guy), Cocca, M. (Massimiliano), Collier, D.A. (David), Cosgrove, C. (Catherine), Cox, T. (Tony), Craddock, N.J. (Nick), Crooks, L. (Lucy), Curran, S. (Sarah), Curtis, D. (David), Daly, A. (Allan), Day, I.N.M. (Ian N.M.), Day-Williams, A.G. (Aaron), Dedoussis, G.V. (George), Down, T. (Thomas), Du, Y. (Yuanping), Duijn, C.M. (Cornelia) van, Dunham, I. (Ian), Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Peter), Evans, D.M. (David), Farooqi, I.S. (I. Sadaf), Fitzpatrick, D.R. (David R.), Flicek, P. (Paul), Floyd, J. (James), Foley, A.R. (A. Reghan), Franklin, C.S. (Christopher S.), Futema, M. (Marta), Gallagher, L. (Louise), Gasparini, P. (Paolo), Gaunt, T.R. (Tom), Geihs, M. (Matthias), Geschwind, D. (Daniel), Greenwood, C.M.T. (Celia), Griffin, H. (Heather), Grozeva, D. (Detelina), Guo, X. (Xiaosen), Guo, X. (Xueqin), Gurling, H. (Hugh), Hart, D. (Deborah), Hendricks, A.E. (Audrey E.), Holmans, P.A. (Peter A.), Huang, L. (Liren), Hubbard, T. (Tim), Humphries, S.E. (Steve E.), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Iotchkova, V. (Valentina), Isaacs, A. (Aaron), Jackson, D.K. (David K.), Jamshidi, Y. (Yalda), Johnson, J. (Jon), Joyce, C. (Chris), Karczewski, K.J. (Konrad), Kaye, J. (Jane), Keane, T. (Thomas), Kemp, J.P. (John), Kennedy, K. (Karen), Kent, A. (Alastair), Keogh, J. (Julia), Khawaja, F. (Farrah), Kleber, M.E. (Marcus), Van Kogelenberg, M. (Margriet), Kolb-Kokocinski, A. (Anja), Kooner, J.S. (Jaspal S.), Lachance, G. (Genevieve), Langenberg, C. (Claudia), Langford, C. (Cordelia), Lawson, D. (Daniel), Lee, I. (Irene), Leeuwen, E.M. (Elisa) van, Lek, M. (Monkol), Li, R. (Rui), Li, Y. (Yingrui), Liang, J. (Jieqin), Lin, H. (Hong), Liu, R. (Ryan), Lönnqvist, J. (Jouko), Lopes, L.R. (Luis R.), Lopes, M.C. (Margarida), Luan, J., MacArthur, D.G. (Daniel G.), Mangino, M. (Massimo), Marenne, G. (Gaëlle), März, W. (Winfried), Maslen, J. (John), Matchan, A. (Angela), Mathieson, I. (Iain), McGuffin, P. (Peter), McIntosh, A.M. (Andrew), McKechanie, A.G. (Andrew G.), McQuillin, A. (Andrew), Metrustry, S. (Sarah), Migone, N. (Nicola), Mitchison, H.M. (Hannah M.), Moayyeri, A. (Alireza), Morris, J. (James), Morris, R.W. (Richard), Muddyman, D. (Dawn), Muntoni, F., Nordestgaard, B.G. (Børge G.), Northstone, K. (Kate), O'donovan, M.C. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A. (Alexandros), Oualkacha, K. (Karim), Owen, M.J. (Michael J.), Palotie, A. (Aarno), Panoutsopoulou, K. (Kalliope), Parker, V. (Victoria), Parr, J.R. (Jeremy R.), Paternoster, L. (Lavinia), Paunio, T. (Tiina), Payne, F. (Felicity), Payne, S.J. (Stewart J.), Perry, J.R.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V. (Vincent), Pollitt, R.C. (Rebecca C.), Povey, S. (Sue), Quail, M.A. (Michael A.), Quaye, L. (Lydia), Raymond, L. (Lucy), Rehnström, K. (Karola), Ridout, C.K. (Cheryl K.), Ring, S.M. (Susan), Ritchie, G.R.S. (Graham R.S.), Roberts, N. (Nicola), Robinson, R.L. (Rachel L.), Savage, D.B. (David), Scambler, P.J. (Peter), Schiffels, S. (Stephan), Schmidts, M. (Miriam), Schoenmakers, N. (Nadia), Scott, R.H. (Richard H.), Scott, R.A. (Robert), Semple, R.K. (Robert K.), Serra, E. (Eva), Sharp, S.I. (Sally I.), Shaw, A.C. (Adam C.), Shihab, H.A. (Hashem A.), Shin, S.-Y. (So-Youn), Skuse, D. (David), Small, K.S. (Kerrin), Smee, C. (Carol), Smith, A.V. (Davey), Southam, L. (Lorraine), Spasic-Boskovic, O. (Olivera), Spector, T.D. (Timothy), St. Clair, D. (David), St Pourcain, B. (Beate), Stalker, J. (Jim), Stevens, E. (Elizabeth), Sun, J. (Jianping), Surdulescu, G. (Gabriela), Suvisaari, J. (Jaana), Syrris, P. (Petros), Tachmazidou, I. (Ioanna), Taylor, R. (Rohan), Tian, J. (Jing), Tobin, M.D. (Martin), Toniolo, D. (Daniela), Traglia, M. (Michela), Tybjaerg-Hansen, A. (Anne), Valdes, A.M., Vandersteen, A.M. (Anthony M.), Varbo, A. (Anette), Vijayarangakannan, P. (Parthiban), Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, J.T. (James), Wang, G. (Guangbiao), Wang, J. (Jun), Wang, Y. (Yu), Ward, K. (Kirsten), Wheeler, E. (Eleanor), Whincup, P.H. (Peter), Whyte, T. (Tamieka), Williams, H.J. (Hywel J.), Williamson, K.A. (Kathleen), Wilson, C. (Crispian), Wilson, S.G. (Scott), Wong, K. (Kim), Xu, C. (Changjiang), Yang, J. (Jian), Zaza, G. (Gianluigi), Zeggini, E. (Eleftheria), Zhang, F. (Feng), Zhang, P. (Pingbo), Zhang, W. (Weihua), Huang, J. (Jie), Howie, B. (Bryan), McCarthy, S. (Shane), Memari, Y. (Yasin), Walter, K. (Klaudia), Min, J.L. (Josine L.), Danecek, P. (Petr), Malerba, G. (Giovanni), Trabetti, E. (Elisabetta), Zheng, H.-F. (Hou-Feng), Gambaro, G. (Giovanni), Richards, J.B. (Brent), Durbin, R. (Richard), Timpson, N.J. (Nicholas), Marchini, J. (Jonathan), Soranzo, N. (Nicole), Al Turki, S.H. (Saeed), Amuzu, A. (Antoinette), Anderson, C. (Carl), Anney, R. (Richard), Antony, D. (Dinu), Artigas, M.S., Ayub, M. (Muhammad), Bala, S. (Senduran), Barrett, J.C. (Jeffrey), Barroso, I.E. (Inês), Beales, P.L. (Philip), Benn, M. (Marianne), Bentham, J. (Jamie), Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D.H.R. (Douglas), Bobrow, M. (Martin), Bochukova, E. (Elena), Bolton, P.F. (Patrick F.), Bounds, R. (Rebecca), Boustred, C. (Chris), Breen, G. (Gerome), Calissano, M. (Mattia), Carss, K. (Keren), Casas, J.P. (Juan Pablo), Chambers, J.C. (John C.), Charlton, R. (Ruth), Chatterjee, K. (Krishna), Chen, L. (Lu), Ciampi, A. (Antonio), Cirak, S. (Sebahattin), Clapham, P. (Peter), Clement, G. (Gail), Coates, G. (Guy), Cocca, M. (Massimiliano), Collier, D.A. (David), Cosgrove, C. (Catherine), Cox, T. (Tony), Craddock, N.J. (Nick), Crooks, L. (Lucy), Curran, S. (Sarah), Curtis, D. (David), Daly, A. (Allan), Day, I.N.M. (Ian N.M.), Day-Williams, A.G. (Aaron), Dedoussis, G.V. (George), Down, T. (Thomas), Du, Y. (Yuanping), Duijn, C.M. (Cornelia) van, Dunham, I. (Ian), Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Peter), Evans, D.M. (David), Farooqi, I.S. (I. Sadaf), Fitzpatrick, D.R. (David R.), Flicek, P. (Paul), Floyd, J. (James), Foley, A.R. (A. Reghan), Franklin, C.S. (Christopher S.), Futema, M. (Marta), Gallagher, L. (Louise), Gasparini, P. (Paolo), Gaunt, T.R. (Tom), Geihs, M. (Matthias), Geschwind, D. (Daniel), Greenwood, C.M.T. (Celia), Griffin, H. (Heather), Grozeva, D. (Detelina), Guo, X. (Xiaosen), Guo, X. (Xueqin), Gurling, H. (Hugh), Hart, D. (Deborah), Hendricks, A.E. (Audrey E.), Holmans, P.A. (Peter A.), Huang, L. (Liren), Hubbard, T. (Tim), Humphries, S.E. (Steve E.), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Iotchkova, V. (Valentina), Isaacs, A. (Aaron), Jackson, D.K. (David K.), Jamshidi, Y. (Yalda), Johnson, J. (Jon), Joyce, C. (Chris), Karczewski, K.J. (Konrad), Kaye, J. (Jane), Keane, T. (Thomas), Kemp, J.P. (John), Kennedy, K. (Karen), Kent, A. (Alastair), Keogh, J. (Julia), Khawaja, F. (Farrah), Kleber, M.E. (Marcus), Van Kogelenberg, M. (Margriet), Kolb-Kokocinski, A. (Anja), Kooner, J.S. (Jaspal S.), Lachance, G. (Genevieve), Langenberg, C. (Claudia), Langford, C. (Cordelia), Lawson, D. (Daniel), Lee, I. (Irene), Leeuwen, E.M. (Elisa) van, Lek, M. (Monkol), Li, R. (Rui), Li, Y. (Yingrui), Liang, J. (Jieqin), Lin, H. (Hong), Liu, R. (Ryan), Lönnqvist, J. (Jouko), Lopes, L.R. (Luis R.), Lopes, M.C. (Margarida), Luan, J., MacArthur, D.G. (Daniel G.), Mangino, M. (Massimo), Marenne, G. (Gaëlle), März, W. (Winfried), Maslen, J. (John), Matchan, A. (Angela), Mathieson, I. (Iain), McGuffin, P. (Peter), McIntosh, A.M. (Andrew), McKechanie, A.G. (Andrew G.), McQuillin, A. (Andrew), Metrustry, S. (Sarah), Migone, N. (Nicola), Mitchison, H.M. (Hannah M.), Moayyeri, A. (Alireza), Morris, J. (James), Morris, R.W. (Richard), Muddyman, D. (Dawn), Muntoni, F., Nordestgaard, B.G. (Børge G.), Northstone, K. (Kate), O'donovan, M.C. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A. (Alexandros), Oualkacha, K. (Karim), Owen, M.J. (Michael J.), Palotie, A. (Aarno), Panoutsopoulou, K. (Kalliope), Parker, V. (Victoria), Parr, J.R. (Jeremy R.), Paternoster, L. (Lavinia), Paunio, T. (Tiina), Payne, F. (Felicity), Payne, S.J. (Stewart J.), Perry, J.R.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V. (Vincent), Pollitt, R.C. (Rebecca C.), Povey, S. (Sue), Quail, M.A. (Michael A.), Quaye, L. (Lydia), Raymond, L. (Lucy), Rehnström, K. (Karola), Ridout, C.K. (Cheryl K.), Ring, S.M. (Susan), Ritchie, G.R.S. (Graham R.S.), Roberts, N. (Nicola), Robinson, R.L. (Rachel L.), Savage, D.B. (David), Scambler, P.J. (Peter), Schiffels, S. (Stephan), Schmidts, M. (Miriam), Schoenmakers, N. (Nadia), Scott, R.H. (Richard H.), Scott, R.A. (Robert), Semple, R.K. (Robert K.), Serra, E. (Eva), Sharp, S.I. (Sally I.), Shaw, A.C. (Adam C.), Shihab, H.A. (Hashem A.), Shin, S.-Y. (So-Youn), Skuse, D. (David), Small, K.S. (Kerrin), Smee, C. (Carol), Smith, A.V. (Davey), Southam, L. (Lorraine), Spasic-Boskovic, O. (Olivera), Spector, T.D. (Timothy), St. Clair, D. (David), St Pourcain, B. (Beate), Stalker, J. (Jim), Stevens, E. (Elizabeth), Sun, J. (Jianping), Surdulescu, G. (Gabriela), Suvisaari, J. (Jaana), Syrris, P. (Petros), Tachmazidou, I. (Ioanna), Taylor, R. (Rohan), Tian, J. (Jing), Tobin, M.D. (Martin), Toniolo, D. (Daniela), Traglia, M. (Michela), Tybjaerg-Hansen, A. (Anne), Valdes, A.M., Vandersteen, A.M. (Anthony M.), Varbo, A. (Anette), Vijayarangakannan, P. (Parthiban), Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, J.T. (James), Wang, G. (Guangbiao), Wang, J. (Jun), Wang, Y. (Yu), Ward, K. (Kirsten), Wheeler, E. (Eleanor), Whincup, P.H. (Peter), Whyte, T. (Tamieka), Williams, H.J. (Hywel J.), Williamson, K.A. (Kathleen), Wilson, C. (Crispian), Wilson, S.G. (Scott), Wong, K. (Kim), Xu, C. (Changjiang), Yang, J. (Jian), Zaza, G. (Gianluigi), Zeggini, E. (Eleftheria), Zhang, F. (Feng), Zhang, P. (Pingbo), and Zhang, W. (Weihua)
Abstract: Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this
Published: 2015
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28. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Author: Huang, J, Howie, B, McCarthy, S, Memari, Y, Walter, K, Min, JL, Danecek, P, Malerba, G, Trabetti, E, Zheng, H-F, Gambaro, G, Richards, JB, Durbin, R, Timpson, NJ, Marchini, J, Soranzo, N, Huang, J, Howie, B, McCarthy, S, Memari, Y, Walter, K, Min, JL, Danecek, P, Malerba, G, Trabetti, E, Zheng, H-F, Gambaro, G, Richards, JB, Durbin, R, Timpson, NJ, Marchini, J, and Soranzo, N
Abstract: Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants.
Published: 2015

29. The UK10K project identifies rare variants in health and disease

Author: Walter, K, Min, JL, Huang, J, Crooks, L, Memari, Y, McCarthy, S, Perry, JRB, Xu, C, Futema, M, Lawson, D, Iotchkova, V, Schiffels, S, Hendricks, AE, Danecek, P, Li, R, Floyd, J, Wain, LV, Barroso, I, Humphries, SE, Hurles, ME, Zeggini, E, Barrett, JC, Plagnol, V, Richards, JB, Greenwood, CMT, Timpson, NJ, Durbin, R, Soranzo, N, Bala, S, Clapham, P, Coates, G, Cox, T, Daly, A, Du, Y, Edkins, S, Ellis, P, Flicek, P, Guo, X, Huang, L, Jackson, DK, Joyce, C, Keane, T, Kolb-Kokocinski, A, Langford, C, Li, Y, Liang, J, Lin, H, Liu, R, Maslen, J, Muddyman, D, Quail, MA, Stalker, J, Sun, J, Tian, J, Wang, G, Wang, J, Wang, Y, Wong, K, Zhang, P, Birney, E, Boustred, C, Chen, L, Clement, G, Cocca, M, Smith, GD, Day, INM, Day-Williams, A, Down, T, Dunham, I, Evans, DM, Gaunt, TR, Geihs, M, Hart, D, Howie, B, Hubbard, T, Hysi, P, Jamshidi, Y, Karczewski, KJ, Kemp, JP, Lachance, G, Lek, M, Lopes, M, MacArthur, DG, Marchini, J, Mangino, M, Mathieson, I, Metrustry, S, Moayyeri, A, Northstone, K, Panoutsopoulou, K, Paternoster, L, Quaye, L, Ring, S, Ritchie, GRS, Shihab, HA, Shin, S-Y, Small, KS, Artigas, MS, Southam, L, Spector, TD, St Pourcain, B, Surdulescu, G, Tachmazidou, I, Tobin, MD, Valdes, AM, Visscher, PM, Ward, K, Wilson, SG, Yang, J, Zhang, F, Zheng, H-F, Anney, R, Ayub, M, Blackwood, D, Bolton, PF, Breen, G, Collier, DA, Craddock, N, Curran, S, Curtis, D, Gallagher, L, Geschwind, D, Gurling, H, Holmans, P, Lee, I, Lonnqvist, J, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Morris, J, O'Donovan, MC, Owen, MJ, Palotie, A, Parr, JR, Paunio, T, Pietilainen, O, Rehnstrom, K, Sharp, SI, Skuse, D, St Clair, D, Suvisaari, J, Walters, JTR, Williams, HJ, Bochukova, E, Bounds, R, Dominiczak, A, Farooqi, IS, Keogh, J, Marenne, GL, Morris, A, O'Rahilly, S, Porteous, DJ, Smith, BH, Wheeler, E, Al Turki, S, Anderson, CA, Antony, D, Beales, P, Bentham, J, Bhattacharya, S, Calissano, M, Carss, K, Chatterjee, K, Cirak, S, Cosgrove, C, Fitzpatrick, DR, Foley, AR, Franklin, CS, Grozeva, D, Mitchison, HM, Muntoni, F, Onoufriadis, A, Parker, V, Payne, F, Raymond, FL, Roberts, N, Savage, DB, Scambler, P, Schmidts, M, Schoenmakers, N, Semple, RK, Serra, E, Spasic-Boskovic, O, Stevens, E, van Kogelenberg, M, Vijayarangakannan, P, Williamson, KA, Wilson, C, Whyte, T, Ciampi, A, Oualkacha, K, Bobrow, M, Griffin, H, Kaye, J, Kennedy, K, Kent, A, Smee, C, Charlton, R, Ekong, R, Khawaja, F, Lopes, LR, Migone, N, Payne, SJ, Pollitt, RC, Povey, S, Ridout, CK, Robinson, RL, Scott, RH, Shaw, A, Syrris, P, Taylor, R, Vandersteen, AM, Amuzu, A, Casas, JP, Chambers, JC, Dedoussis, G, Gambaro, G, Gasparini, P, Isaacs, A, Johnson, J, Kleber, ME, Kooner, JS, Langenberg, C, Luan, J, Malerba, G, Maerz, W, Matchan, A, Morris, R, Nordestgaard, BG, Benn, M, Scott, RA, Toniolo, D, Traglia, M, Tybjaerg-Hansen, A, van Duijn, CM, van Leeuwen, EM, Varbo, A, Whincup, P, Zaza, G, Zhang, W, Walter, K, Min, JL, Huang, J, Crooks, L, Memari, Y, McCarthy, S, Perry, JRB, Xu, C, Futema, M, Lawson, D, Iotchkova, V, Schiffels, S, Hendricks, AE, Danecek, P, Li, R, Floyd, J, Wain, LV, Barroso, I, Humphries, SE, Hurles, ME, Zeggini, E, Barrett, JC, Plagnol, V, Richards, JB, Greenwood, CMT, Timpson, NJ, Durbin, R, Soranzo, N, Bala, S, Clapham, P, Coates, G, Cox, T, Daly, A, Du, Y, Edkins, S, Ellis, P, Flicek, P, Guo, X, Huang, L, Jackson, DK, Joyce, C, Keane, T, Kolb-Kokocinski, A, Langford, C, Li, Y, Liang, J, Lin, H, Liu, R, Maslen, J, Muddyman, D, Quail, MA, Stalker, J, Sun, J, Tian, J, Wang, G, Wang, J, Wang, Y, Wong, K, Zhang, P, Birney, E, Boustred, C, Chen, L, Clement, G, Cocca, M, Smith, GD, Day, INM, Day-Williams, A, Down, T, Dunham, I, Evans, DM, Gaunt, TR, Geihs, M, Hart, D, Howie, B, Hubbard, T, Hysi, P, Jamshidi, Y, Karczewski, KJ, Kemp, JP, Lachance, G, Lek, M, Lopes, M, MacArthur, DG, Marchini, J, Mangino, M, Mathieson, I, Metrustry, S, Moayyeri, A, Northstone, K, Panoutsopoulou, K, Paternoster, L, Quaye, L, Ring, S, Ritchie, GRS, Shihab, HA, Shin, S-Y, Small, KS, Artigas, MS, Southam, L, Spector, TD, St Pourcain, B, Surdulescu, G, Tachmazidou, I, Tobin, MD, Valdes, AM, Visscher, PM, Ward, K, Wilson, SG, Yang, J, Zhang, F, Zheng, H-F, Anney, R, Ayub, M, Blackwood, D, Bolton, PF, Breen, G, Collier, DA, Craddock, N, Curran, S, Curtis, D, Gallagher, L, Geschwind, D, Gurling, H, Holmans, P, Lee, I, Lonnqvist, J, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Morris, J, O'Donovan, MC, Owen, MJ, Palotie, A, Parr, JR, Paunio, T, Pietilainen, O, Rehnstrom, K, Sharp, SI, Skuse, D, St Clair, D, Suvisaari, J, Walters, JTR, Williams, HJ, Bochukova, E, Bounds, R, Dominiczak, A, Farooqi, IS, Keogh, J, Marenne, GL, Morris, A, O'Rahilly, S, Porteous, DJ, Smith, BH, Wheeler, E, Al Turki, S, Anderson, CA, Antony, D, Beales, P, Bentham, J, Bhattacharya, S, Calissano, M, Carss, K, Chatterjee, K, Cirak, S, Cosgrove, C, Fitzpatrick, DR, Foley, AR, Franklin, CS, Grozeva, D, Mitchison, HM, Muntoni, F, Onoufriadis, A, Parker, V, Payne, F, Raymond, FL, Roberts, N, Savage, DB, Scambler, P, Schmidts, M, Schoenmakers, N, Semple, RK, Serra, E, Spasic-Boskovic, O, Stevens, E, van Kogelenberg, M, Vijayarangakannan, P, Williamson, KA, Wilson, C, Whyte, T, Ciampi, A, Oualkacha, K, Bobrow, M, Griffin, H, Kaye, J, Kennedy, K, Kent, A, Smee, C, Charlton, R, Ekong, R, Khawaja, F, Lopes, LR, Migone, N, Payne, SJ, Pollitt, RC, Povey, S, Ridout, CK, Robinson, RL, Scott, RH, Shaw, A, Syrris, P, Taylor, R, Vandersteen, AM, Amuzu, A, Casas, JP, Chambers, JC, Dedoussis, G, Gambaro, G, Gasparini, P, Isaacs, A, Johnson, J, Kleber, ME, Kooner, JS, Langenberg, C, Luan, J, Malerba, G, Maerz, W, Matchan, A, Morris, R, Nordestgaard, BG, Benn, M, Scott, RA, Toniolo, D, Traglia, M, Tybjaerg-Hansen, A, van Duijn, CM, van Leeuwen, EM, Varbo, A, Whincup, P, Zaza, G, and Zhang, W
Abstract: The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.
Published: 2015

30. Whole-genome sequence-based analysis of thyroid function.

Author: Taylor, PN, Porcu, E, Chew, S, Campbell, PJ, Traglia, M, Brown, SJ, Mullin, BH, Shihab, HA, Min, J, Walter, K, Memari, Y, Huang, J, Barnes, MR, Beilby, JP, Charoen, P, Danecek, P, Dudbridge, F, Forgetta, V, Greenwood, C, Grundberg, E, Johnson, AD, Hui, J, Lim, EM, McCarthy, S, Muddyman, D, Panicker, V, Perry, JRB, Bell, JT, Yuan, W, Relton, C, Gaunt, T, Schlessinger, D, Abecasis, G, Cucca, F, Surdulescu, GL, Woltersdorf, W, Zeggini, E, Zheng, H-F, Toniolo, D, Dayan, CM, Naitza, S, Walsh, JP, Spector, T, Davey Smith, G, Durbin, R, Richards, JB, Sanna, S, Soranzo, N, Timpson, NJ, Wilson, SG, UK0K Consortium, Taylor, PN, Porcu, E, Chew, S, Campbell, PJ, Traglia, M, Brown, SJ, Mullin, BH, Shihab, HA, Min, J, Walter, K, Memari, Y, Huang, J, Barnes, MR, Beilby, JP, Charoen, P, Danecek, P, Dudbridge, F, Forgetta, V, Greenwood, C, Grundberg, E, Johnson, AD, Hui, J, Lim, EM, McCarthy, S, Muddyman, D, Panicker, V, Perry, JRB, Bell, JT, Yuan, W, Relton, C, Gaunt, T, Schlessinger, D, Abecasis, G, Cucca, F, Surdulescu, GL, Woltersdorf, W, Zeggini, E, Zheng, H-F, Toniolo, D, Dayan, CM, Naitza, S, Walsh, JP, Spector, T, Davey Smith, G, Durbin, R, Richards, JB, Sanna, S, Soranzo, N, Timpson, NJ, Wilson, SG, and UK0K Consortium
Abstract: Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P=6.15 × 10(-9)) and a new independent variant in PDE8B (MAF=10.4%, P=5.94 × 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P=1.27 × 10(-9)) tagging a rare TTR variant (MAF=0.4%, P=2.14 × 10(-11)). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF<1%) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.
Published: 2015

31. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

Author: Zheng, HF, Forgetta, V, Hsu, YH, Estrada, K, Rosello-Diez, A, Leo, PJ, Dahia, CL, Park-Min, KH, Tobias, JH, Kooperberg, C, Kleinman, A, Styrkarsdottir, U, Liu, CT, Uggla, C, Evans, DS, Nielson, CM, Walter, K, Pettersson-Kymmer, U, McCarthy, S, Eriksson, J, Kwan, T, Jhamai, M, Trajanoska, K, Memari, Y, Min, J, Huang, J, Danecek, P, Wilmot, B, Li, R, Chou, WC, Mokry, LE, Moayyeri, A, Claussnitzer, M, Cheng, CH, Cheung, W, Medina-Gómez, C, Ge, B, Chen, SH, Choi, K, Oei, L, Fraser, J, Kraaij, R, Hibbs, MA, Gregson, CL, Paquette, D, Hofman, A, Wibom, C, Tranah, GJ, Marshall, M, Gardiner, BB, Cremin, K, Auer, P, Hsu, L, Ring, S, Tung, JY, Thorleifsson, G, Enneman, AW, Van Schoor, NM, De Groot, LCPGM, Van Der Velde, N, Melin, B, Kemp, JP, Christiansen, C, Sayers, A, Zhou, Y, Calderari, S, Van Rooij, J, Carlson, C, Peters, U, Berlivet, S, Dostie, J, Uitterlinden, AG, Williams, SR, Farber, C, Grinberg, D, LaCroix, AZ, Haessler, J, Chasman, DI, Giulianini, F, Rose, LM, Ridker, PM, Eisman, JA, Nguyen, TV, Center, JR, Nogues, X, Garcia-Giralt, N, Launer, LL, Gudnason, V, Mellström, D, Vandenput, L, Amin, N, Van Duijn, CM, Karlsson, MK, Ljunggren, Ö, Svensson, O, Hallmans, G, Rousseau, F, Giroux, S, Bussière, J, Arp, PP, Zheng, HF, Forgetta, V, Hsu, YH, Estrada, K, Rosello-Diez, A, Leo, PJ, Dahia, CL, Park-Min, KH, Tobias, JH, Kooperberg, C, Kleinman, A, Styrkarsdottir, U, Liu, CT, Uggla, C, Evans, DS, Nielson, CM, Walter, K, Pettersson-Kymmer, U, McCarthy, S, Eriksson, J, Kwan, T, Jhamai, M, Trajanoska, K, Memari, Y, Min, J, Huang, J, Danecek, P, Wilmot, B, Li, R, Chou, WC, Mokry, LE, Moayyeri, A, Claussnitzer, M, Cheng, CH, Cheung, W, Medina-Gómez, C, Ge, B, Chen, SH, Choi, K, Oei, L, Fraser, J, Kraaij, R, Hibbs, MA, Gregson, CL, Paquette, D, Hofman, A, Wibom, C, Tranah, GJ, Marshall, M, Gardiner, BB, Cremin, K, Auer, P, Hsu, L, Ring, S, Tung, JY, Thorleifsson, G, Enneman, AW, Van Schoor, NM, De Groot, LCPGM, Van Der Velde, N, Melin, B, Kemp, JP, Christiansen, C, Sayers, A, Zhou, Y, Calderari, S, Van Rooij, J, Carlson, C, Peters, U, Berlivet, S, Dostie, J, Uitterlinden, AG, Williams, SR, Farber, C, Grinberg, D, LaCroix, AZ, Haessler, J, Chasman, DI, Giulianini, F, Rose, LM, Ridker, PM, Eisman, JA, Nguyen, TV, Center, JR, Nogues, X, Garcia-Giralt, N, Launer, LL, Gudnason, V, Mellström, D, Vandenput, L, Amin, N, Van Duijn, CM, Karlsson, MK, Ljunggren, Ö, Svensson, O, Hallmans, G, Rousseau, F, Giroux, S, Bussière, J, and Arp, PP
Abstract: © 2015 Macmillan Publishers Limited. All rights reserved. The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10-14), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10-11; ncases = 98,742 and n controls = 409,511). Using an En1 cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10-11). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for wh
Published: 2015

32. The QUaD Galactic Plane Survey. II

Author: Culverhouse, T., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Friedman, R., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Pryke, C., Schwarz, R., O'Sullivan, C., Piccirillo, L., Rajguru, N., Rusholme, B., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Published: 2011
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33. Phenotypic spectrum of eleven patients and five novel MTFMT mutations identified by exome sequencing and candidate gene screening

Author: Haack, T.B., Gorza, M., Danhauser, K., Mayr, J.A., Haberberger, B., Wieland, T., Kremer, L., Strecker, V., Graf, E., Memari, Y., Ahting, U., Kopajtich, R., Wortmann, S.B., Rodenburg, R.J.T., Kotzaeridou, U., Hoffmann, G.F., Sperl, W., Wittig, I., Wilichowski, E., Schottmann, G., Schuelke, M., Plecko, B., Stephani, U., Strom, T.M., Meitinger, T., Prokisch, H., Freisinger, P., Haack, T.B., Gorza, M., Danhauser, K., Mayr, J.A., Haberberger, B., Wieland, T., Kremer, L., Strecker, V., Graf, E., Memari, Y., Ahting, U., Kopajtich, R., Wortmann, S.B., Rodenburg, R.J.T., Kotzaeridou, U., Hoffmann, G.F., Sperl, W., Wittig, I., Wilichowski, E., Schottmann, G., Schuelke, M., Plecko, B., Stephani, U., Strom, T.M., Meitinger, T., Prokisch, H., and Freisinger, P.
Abstract: Item does not contain fulltext, Defects of mitochondrial oxidative phosphorylation (OXPHOS) are associated with a wide range of clinical phenotypes and time courses. Combined OXPHOS deficiencies are mainly caused by mutations of nuclear genes that are involved in mitochondrial protein translation. Due to their genetic heterogeneity it is almost impossible to diagnose OXPHOS patients on clinical grounds alone. Hence next generation sequencing (NGS) provides a distinct advantage over candidate gene sequencing to discover the underlying genetic defect in a timely manner. One recent example is the identification of mutations in MTFMT that impair mitochondrial protein translation through decreased formylation of Met-tRNA(Met). Here we report the results of a combined exome sequencing and candidate gene screening study. We identified nine additional MTFMT patients from eight families who were affected with Leigh encephalopathy or white matter disease, microcephaly, mental retardation, ataxia, and muscular hypotonia. In four patients, the causal mutations were identified by exome sequencing followed by stringent bioinformatic filtering. In one index case, exome sequencing identified a single heterozygous mutation leading to Sanger sequencing which identified a second mutation in the non-covered first exon. High-resolution melting curve-based MTFMT screening in 350 OXPHPOS patients identified pathogenic mutations in another three index cases. Mutations in one of them were not covered by previous exome sequencing. All novel mutations predict a loss-of-function or result in a severe decrease in MTFMT protein in patients' fibroblasts accompanied by reduced steady-state levels of complex I and IV subunits. Being present in 11 out of 13 index cases the c.626C>T mutation is one of the most frequent disease alleles underlying OXPHOS disorders. We provide detailed clinical descriptions on eleven MTFMT patients and review five previously reported cases.
Published: 2014

34. A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.

Author: Timpson, NJ, Walter, K, Min, JL, Tachmazidou, I, Malerba, G, Shin, S-Y, Chen, L, Futema, M, Southam, L, Iotchkova, V, Cocca, M, Huang, J, Memari, Y, McCarthy, S, Danecek, P, Muddyman, D, Mangino, M, Menni, C, Perry, JRB, Ring, SM, Gaye, A, Dedoussis, G, Farmaki, A-E, Burton, P, Talmud, PJ, Gambaro, G, Spector, TD, Smith, GD, Durbin, R, Richards, JB, Humphries, SE, Zeggini, E, Soranzo, N, UK1OK Consortium Members, Timpson, NJ, Walter, K, Min, JL, Tachmazidou, I, Malerba, G, Shin, S-Y, Chen, L, Futema, M, Southam, L, Iotchkova, V, Cocca, M, Huang, J, Memari, Y, McCarthy, S, Danecek, P, Muddyman, D, Mangino, M, Menni, C, Perry, JRB, Ring, SM, Gaye, A, Dedoussis, G, Farmaki, A-E, Burton, P, Talmud, PJ, Gambaro, G, Spector, TD, Smith, GD, Durbin, R, Richards, JB, Humphries, SE, Zeggini, E, Soranzo, N, and UK1OK Consortium Members
Abstract: The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (-1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10(-8))) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (-1.0 s.d. (s.e.=0.173), P-value=7.32 × 10(-9)). This is consistent with an effect between 0.5 and 1.5 mmol l(-1) dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale.
Published: 2014

35. Cosmological Parameters from the QUaD CMB Polarization Experiment

Author: Brown, Michael, Castro, P. G., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Church, S., Culverhouse, T., Friedman, R. B., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Pryke, C., Schwarz, R., O'Sullivan, C., Piccirillo, L., Rajguru, N., Rusholme, B., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y S, Zemcov, M., APC - Cosmologie, AstroParticule et Cosmologie (APC (UMR_7164)), Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), QUaD, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Physique Corpusculaire et Cosmologie - Collège de France (PCC), and Collège de France (CdF)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS)
Subjects: cosmic microwave background, Cosmology and Nongalactic Astrophysics (astro-ph.CO), Statistical [Methods], Cold dark matter, [SDU.ASTR.CO]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], Physics beyond the Standard Model, Cosmological parameters, Cosmic microwave background, FOS: Physical sciences, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics, 01 natural sciences, Cosmology, [PHYS.ASTR.CO]Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], Polarization, 0103 physical sciences, cosmological parameters, 010303 astronomy & astrophysics, Physics, methods: statistical, polarization, 010308 nuclear & particles physics, Spectral density, Astronomy and Astrophysics, CMB cold spot, Galaxy, Space and Planetary Science, Neutrino, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract: In this paper we present a parameter estimation analysis of the polarization and temperature power spectra from the second and third season of observations with the QUaD experiment. QUaD has for the first time detected multiple acoustic peaks in the E-mode polarization spectrum with high significance. Although QUaD-only parameter constraints are not competitive with previous results for the standard 6-parameter LCDM cosmology, they do allow meaningful polarization-only parameter analyses for the first time. In a standard 6-parameter LCDM analysis we find the QUaD TT power spectrum to be in good agreement with previous results. However, the QUaD polarization data shows some tension with LCDM. The origin of this 1 to 2 sigma tension remains unclear, and may point to new physics, residual systematics or simple random chance. We also combine QUaD with the five-year WMAP data set and the SDSS Luminous Red Galaxies 4th data release power spectrum, and extend our analysis to constrain individual isocurvature mode fractions, constraining cold dark matter density, alpha(cdmi), 8 pages, 5 figures, submitted to ApJ
Published: 2009
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36. Cosmological Parameters from the QUaD CMB Polarization Experiment

Author: Castro, P.G., Ade, P., Bock, J., Bowden, M.L., Brown, M.L., Cahill, G., Church, S., Culverhouse, T., Friedman, R.B., Ganga, K., Gear, W.K., Gupta, S., Hinderks, J., Kovac, J., Lange, A.E., Leitch, E., Melhuish, S.J., Memari, Y., Murphy, J.A., Orlando, A., Pryke, C., Schwarz, R., O'Sullivan, C., Piccirillo, L., Taylor, A.N., Thompson, K.L., Turner, A.H., Wu, E.Y.S., and Zemcov, M.
Subjects: Experimental Physics, Astrophysics::Cosmology and Extragalactic Astrophysics
Abstract: In this paper, we present a parameter estimation analysis of the polarization and temperature power spectra from the second and third season of observations with the QUaD experiment. QUaD has for the first time detected multiple acoustic peaks in the E-mode polarization spectrum with high significance. Although QUaD-only parameter constraints are not competitive with previous results for the standard six-parameter ΛCDM cosmology, they do allow meaningful polarization-only parameter analyses for the first time. In a standard six-parameter ΛCDM analysis, we find the QUaD TT power spectrum to be in good agreement with previous results. However, the QUaD polarization data show some tension with ΛCDM. The origin of this 1σ–2σ tension remains unclear, and may point to new physics, residual systematics, or simple random chance. We also combine QUaD with the five-year WMAP data set and the SDSS luminous red galaxies 4th data release power spectrum, and extend our analysis to constrain individual isocurvature mode fractions, constraining cold dark matter density, αcdmi < 0.11 (95% confidence limit (CL)), neutrino density, αndi < 0.26 (95% CL), and neutrino velocity, αnvi < 0.23 (95% CL), modes. Our analysis sets a benchmark for future polarization experiments.
Published: 2009

37. QUaD: A High-Resolution Cosmic Microwave Background Polarimeter

Author: Hinderks, J., Ade, P., Bock, J., Bowden, M.L., Cahill, G., Carlstrom, J.E., Castro, P.G., Church, S., Culverhouse, T., Friedman, R., Ganga, K., Gear, W.K., Gupta, S., Harris, J., Haynes, V., Keating, B.G., Kovac, J., Kirby, E., Lange, A.E., Leitch, E., Mallie, O.E., Melhuish, S., Memari, Y., Murphy, A., Orlando, A., Schwarz, R., O'Sullivan, C., Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Taylor, A.N., Thompson, K.L., Tucker, C., Turner, A.H., Wu, E.Y.S., and Zemcov, M.
Subjects: Experimental Physics, Astrophysics::Instrumentation and Methods for Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics::Galaxy Astrophysics
Abstract: We describe the QUaD experiment, a millimeter-wavelength polarimeter designed to observe the cosmic microwave background (CMB) from a site at the South Pole. The experiment comprises a 2.64 m Cassegrain telescope equipped with a cryogenically cooled receiver containing an array of 62 polarization-sensitive bolometers. The focal plane contains pixels at two different frequency bands, 100 GHz and 150 GHz, with angular resolutions of 5 and 3.5, respectively. The high angular resolution allows observation of CMB temperature and polarization anisotropies over a wide range of scales. The instrument commenced operation in early 2005 and collected science data during three successive Austral winter seasons of observation.
Published: 2009

38. Seventy-five genetic loci influencing the human red blood cell

Author: van der Harst, P., Zhang, W., Mateo Leach, I., Rendon, A., Verweij, N., Sehmi, J., Paul, D.S., Elling, U., Allayee, H., Li, X., Radhakrishnan, A., Tan, S.T., Voss, K., Weichenberger, C.X., Albers, C.A., Al-Hussani, A., Asselbergs, F.W., Ciullo, M., Danjou, F., Dina, C., Esko, T., Evans, D.M., Franke, L., Gogele, M., Hartiala, J., Hersch, M., Holm, H., Hottenga, J.J., Kanoni, S., Kleber, M.E., Lagou, V., Langenberg, C., Lopez, L.M., Lyytikainen, L.P., Melander, O., Murgia, F., Nolte, I.M., O'Reilly, P.F., Padmanabhan, S., Parsa, A., Pirastu, N., Porcu, E., Portas, L., Prokopenko, I., Ried, J.S., Shin, S.Y., Tang, C.S., Teumer, A., Traglia, M., Ulivi, S., Westra, H.J., Yang, J., Zhao, J.H., Anni, F., Abdellaoui, A., Attwood, A., Balkau, B., Bandinelli, S., Bastardot, F., Benyamin, B., Boehm, B.O., Cookson, W.O., Das, D, de Bakker, P.I., de Boer, R.A., de Geus, E.J., de Moor, M.H., Dimitriou, M., Domingues, F.S., Doring, A., Engstrom, G., Eyjolfsson, G.I., Ferrucci, L., Fischer, K., Galanello, R., Garner, S.F., Genser, B., Gibson, Q.D., Girotto, G., Gudbjartsson, D.F., Harris, S.E., Hartikainen, A.L., Hastie, C.E., Hedblad, B., Illig, T., Jolley, J., Kahonen, M., Kema, I.P., Kemp, J.P., Liang, L., Lloyd-Jones, H., Loos, R.J., Meacham, S., Medland, S.E., Meisinger, C., Memari, Y., Mihailov, E., Miller, K., Moffatt, M.F., Nauck, M., et al., van der Harst, P., Zhang, W., Mateo Leach, I., Rendon, A., Verweij, N., Sehmi, J., Paul, D.S., Elling, U., Allayee, H., Li, X., Radhakrishnan, A., Tan, S.T., Voss, K., Weichenberger, C.X., Albers, C.A., Al-Hussani, A., Asselbergs, F.W., Ciullo, M., Danjou, F., Dina, C., Esko, T., Evans, D.M., Franke, L., Gogele, M., Hartiala, J., Hersch, M., Holm, H., Hottenga, J.J., Kanoni, S., Kleber, M.E., Lagou, V., Langenberg, C., Lopez, L.M., Lyytikainen, L.P., Melander, O., Murgia, F., Nolte, I.M., O'Reilly, P.F., Padmanabhan, S., Parsa, A., Pirastu, N., Porcu, E., Portas, L., Prokopenko, I., Ried, J.S., Shin, S.Y., Tang, C.S., Teumer, A., Traglia, M., Ulivi, S., Westra, H.J., Yang, J., Zhao, J.H., Anni, F., Abdellaoui, A., Attwood, A., Balkau, B., Bandinelli, S., Bastardot, F., Benyamin, B., Boehm, B.O., Cookson, W.O., Das, D, de Bakker, P.I., de Boer, R.A., de Geus, E.J., de Moor, M.H., Dimitriou, M., Domingues, F.S., Doring, A., Engstrom, G., Eyjolfsson, G.I., Ferrucci, L., Fischer, K., Galanello, R., Garner, S.F., Genser, B., Gibson, Q.D., Girotto, G., Gudbjartsson, D.F., Harris, S.E., Hartikainen, A.L., Hastie, C.E., Hedblad, B., Illig, T., Jolley, J., Kahonen, M., Kema, I.P., Kemp, J.P., Liang, L., Lloyd-Jones, H., Loos, R.J., Meacham, S., Medland, S.E., Meisinger, C., Memari, Y., Mihailov, E., Miller, K., Moffatt, M.F., and Nauck, M., et al.
Abstract: Item does not contain fulltext, Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
Published: 2012

39. Polarization Calibration of the QUaD Experiment

Author: Hinderks, J., Ade, P.A.R., Bock, J.J., Bowden, M., Brown, M.L., Cahill, G., Carlstrom, J.E., Castro, P.G., Church, S., Culverhouse, T., Friedman, R., Ganga, K., Gear, W.K., Gupta, S., Harris, J., Haynes, V., Kovac, J., Lange, A.E., Leitch, E., Mallie, O.E., Melhuish, S.J., Memari, Y., Murphy, J.Anthony, Orlando, A., Schwarz, R., O'Sullivan, Créidhe, Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Taylor, A.N., Thompson, K.L., Tucker, C., Turner, A.H., Wu, E.Y.S., Zemcov, M., Hinderks, J., Ade, P.A.R., Bock, J.J., Bowden, M., Brown, M.L., Cahill, G., Carlstrom, J.E., Castro, P.G., Church, S., Culverhouse, T., Friedman, R., Ganga, K., Gear, W.K., Gupta, S., Harris, J., Haynes, V., Kovac, J., Lange, A.E., Leitch, E., Mallie, O.E., Melhuish, S.J., Memari, Y., Murphy, J.Anthony, Orlando, A., Schwarz, R., O'Sullivan, Créidhe, Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Taylor, A.N., Thompson, K.L., Tucker, C., Turner, A.H., Wu, E.Y.S., and Zemcov, M.
Abstract: We describe the polarization calibration of the QUaD experiment, including determination of the polarization efficiency of the detectors and their orientation angles. QUaD is a millimeter-wavelength polarimeter that observed the Cosmic Microwave Background (CMB) from a site at the South Pole. The experiment comprises a 2.64 m Cassegrain telescope equipped with a cryogenically cooled receiver containing an array of 62 polarization-sensitive bolometers. The focal plane contains pixels at two different frequency bands, 100 GHz and 150 GHz, with angular resolutions of 5prime and 3farcm5, respectively. The high angular resolution allows observation of CMB temperature and polarization anisotropies over a wide range of scales. The instrument commenced operation in early 2005 and collected science data during three successive Austral winter seasons of observation.
Published: 2011

40. Characterization of the Millimeter-Wave Polarization of Centaurus A with Quad

Author: Zemcov, M., Ade, P.A.R., Bock, J.J., Bowden, M., Brown, M.L., Cahill, G., Castro, P.G., Church, S., Culverhouse, T., Freidman, R.B., Ganga, K., Gear, W.K., Gupta, S., Hinderks, J., Kovac, J., Lange, A.E., Leitch, E., Melhuish, S.J., Memari, Y., Murphy, J.Anthony, Orlando, A., O'Sullivan, Créidhe, Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., Taylor, A.N., Thompson, K.L., Turner, A.H., Wu, E.Y.S., Zemcov, M., Ade, P.A.R., Bock, J.J., Bowden, M., Brown, M.L., Cahill, G., Castro, P.G., Church, S., Culverhouse, T., Freidman, R.B., Ganga, K., Gear, W.K., Gupta, S., Hinderks, J., Kovac, J., Lange, A.E., Leitch, E., Melhuish, S.J., Memari, Y., Murphy, J.Anthony, Orlando, A., O'Sullivan, Créidhe, Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., Taylor, A.N., Thompson, K.L., Turner, A.H., and Wu, E.Y.S.
Abstract: Centaurus (Cen) A represents one of the best candidates for an isolated, compact, highly polarized source that is bright at typical cosmic microwave background (CMB) experiment frequencies. We present measurements of the 4°×2° region centered on Cen A with QUaD, a CMB polarimeter whose absolute polarization angle is known to 0°.5. Simulations are performed to assess the effect of misestimation of the instrumental parameters on the final measurement, and systematic errors due to the field’s background structure and temporal variability from Cen A’s nuclear region are determined. The total (Q,U) of the inner lobe region is (1.00±0.07(stat.)± 0.04(sys.),-1.72±0.06±0.05) Jy at 100 GHz and (0.80±0.06±0.06,-1.40±0.07±0.08) Jy at 150 GHz, leading to polarization angles and total errors of -30°.0±1°.1 and -29°.1±1°.7. These measurements will allow the use of Cen A as a polarized calibration source for future millimeter experiments
Published: 2010

41. Second and Third Season QUaD Cosmic Microwave Background Temperature and Polarization Power Spectra

Author: Pryke, C., Ade, P.A.R., Bock, J.J., Bowden, M., Brown, M.L., Cahill, G., Castro, P.G., Church, S., Culverhouse, T., Friedman, R., Ganga, K., Gear, W.K., Gupta, S., Hinderks, J., Kovac, J., Lange, A.E., Leitch, E., Melhuish, S.J., Memari, Y., Murphy, J.Anthony, Orlando, A., Schwarz, R., O'Sullivan, Créidhe, Piccirillo, L., Rajguru, N., Rusholme, B., Taylor, A.N., Thompson, K.L., Turner, A.H., Wu, E.Y.S., Zemcov, M., Pryke, C., Ade, P.A.R., Bock, J.J., Bowden, M., Brown, M.L., Cahill, G., Castro, P.G., Church, S., Culverhouse, T., Friedman, R., Ganga, K., Gear, W.K., Gupta, S., Hinderks, J., Kovac, J., Lange, A.E., Leitch, E., Melhuish, S.J., Memari, Y., Murphy, J.Anthony, Orlando, A., Schwarz, R., O'Sullivan, Créidhe, Piccirillo, L., Rajguru, N., Rusholme, B., Taylor, A.N., Thompson, K.L., Turner, A.H., Wu, E.Y.S., and Zemcov, M.
Abstract: We report results from the second and third seasons of observation with the QUaD experiment. Angular power spectra of the cosmic microwave background are derived for both temperature and polarization at both 100 GHz and 150 GHz, and as cross-frequency spectra. All spectra are subjected to an extensive set of jackknife tests to probe for possible systematic contamination. For the implemented data cuts and processing technique such contamination is undetectable. We analyze the difference map formed between the 100 and 150 GHz bands and find no evidence of foreground contamination in polarization. The spectra are then combined to form a single set of results which are shown to be consistent with the prevailing LCDM model. The sensitivity of the polarization results is considerably better than that of any previous experiment— for the first time multiple acoustic peaks are detected in the E-mode power spectrum at high significance.
Published: 2009

42. Parity Violation Constraints Using Cosmic Microwave Background Polarization Spectra from 2006 and 2007 Observations by the QUaD Polarimeter

Author: Wu, E.Y.S., Ade, P.A.R., Bock, J.J., Bowden, M., Brown, M.L., Cahill, G., Castro, P.G., Church, S., Culverhouse, T., Friedman, R.B., Ganga, K., Gear, W.K., Gupta, S., Hinderks, J., Kovac, J., Lange, A.E., Leitch, E., Melhuish, S.J., Memari, Y., Murphy, J.Anthony, Orlando, A., Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., O'Sullivan, Créidhe, Taylor, A.N., Thompson, K.L., Turner, A.H., Zemcov, M., Wu, E.Y.S., Ade, P.A.R., Bock, J.J., Bowden, M., Brown, M.L., Cahill, G., Castro, P.G., Church, S., Culverhouse, T., Friedman, R.B., Ganga, K., Gear, W.K., Gupta, S., Hinderks, J., Kovac, J., Lange, A.E., Leitch, E., Melhuish, S.J., Memari, Y., Murphy, J.Anthony, Orlando, A., Piccirillo, L., Pryke, C., Rajguru, N., Rusholme, B., Schwarz, R., O'Sullivan, Créidhe, Taylor, A.N., Thompson, K.L., Turner, A.H., and Zemcov, M.
Abstract: We constrain parity-violating interactions to the surface of last scattering using spectra from the QUaD experiment’s second and third seasons of observations by searching for a possible systematic rotation of the polarization directions of cosmic microwave background photons. We measure the rotation angle due to such a possible “cosmological birefringence” to be 0.55°±0.82° (random) ±0.5° (systematic) using QUaD’s 100 and 150 GHz temperature-curl and gradient-curl spectra over the spectra over the multipole range 200<ℓ<2000, consistent with null, and constrain Lorentz-violating interactions to <2×10-43 GeV (68% confidence limit). This is the best constraint to date on electrodynamic parity violation on cosmological scales.
Published: 2009

43. Oral Abstracts 7: RA Clinical * O37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Author: Fleischmann, R., primary, van Vollenhoven, R. F., additional, Smolen, J., additional, Emery, P., additional, Florentinus, S., additional, Rathmann, S., additional, Kupper, H., additional, Kavanaugh, A., additional, Taylor, P., additional, Genovese, M., additional, Keystone, E. C., additional, Drescher, E., additional, Berclaz, P.-Y., additional, Lee, C., additional, Fidelus-Gort, R., additional, Schlichting, D., additional, Beattie, S., additional, Luchi, M., additional, Macias, W., additional, Dikranian, A. H., additional, Alten, R., additional, Klearman, M., additional, Musselman, D., additional, Agarwal, S., additional, Green, J., additional, Gabay, C., additional, Weinblatt, M. E., additional, Schiff, M. H., additional, Fleischmann, R., additional, Valente, R., additional, van der Heijde, D., additional, Citera, G., additional, Zhao, C., additional, Maldonado, M. A., additional, Rakieh, C., additional, Nam, J. L., additional, Hunt, L., additional, Villeneuve, E., additional, Bissell, L.-A., additional, Das, S., additional, Conaghan, P., additional, McGonagle, D., additional, Wakefield, R. J., additional, Wright, H. L., additional, Thomas, H. B., additional, Moots, R., additional, Edwards, S. W., additional, Hamann, P., additional, Heward, J., additional, McHugh, N., additional, Lindsay, M. A., additional, Haroon, M., additional, Giles, J. T., additional, Winchester, R., additional, FitzGerald, O., additional, Karaderi, T., additional, Cohen, C. J., additional, Keidel, S., additional, Appleton, L. H., additional, Macfarlane, G. J., additional, Siebert, S., additional, Evans, D., additional, Paul Wordsworth, B., additional, Plant, D., additional, Bowes, J., additional, Orozco, G., additional, Morgan, A. W., additional, Wilson, A. G., additional, Isaacs, J., additional, Barton, A., additional, Williams, F. M., additional, Livshits, G., additional, Spector, T., additional, MacGregor, A., additional, Scollen, S., additional, Cao, D., additional, Memari, Y., additional, Hyde, C. L., additional, Zhang, B., additional, Sidders, B., additional, Ziemek, D., additional, Shi, Y., additional, Harris, J., additional, Harrow, I., additional, Dougherty, B., additional, Malarstig, A., additional, McEwen, R., additional, Stephens, J. L., additional, Patel, K., additional, Shin, S.-Y., additional, Surdulescu, G., additional, He, W., additional, Jin, X., additional, McMahon, S. B., additional, Soranzo, N., additional, John, S., additional, Wang, J., additional, Spector, T. D., additional, Baker, J., additional, Litherland, G. J., additional, Rowan, A. D., additional, Kite, K. A., additional, Bayley, R., additional, Yang, P., additional, Smith, J. P., additional, Williams, J., additional, Harper, L., additional, Kitas, G. D., additional, Buckley, C., additional, Young, S. P., additional, Fitzpatrick, M. A., additional, McGettrick, H. M., additional, Filer, A., additional, Raza, K., additional, Nash, G., additional, Muthana, M., additional, Davies, H., additional, Khetan, S., additional, Adeleke, G., additional, Hawtree, S., additional, Tazzyman, S., additional, Morrow, F., additional, Ciani, B., additional, Wilson, G., additional, Quirke, A.-M., additional, Lugli, E., additional, Wegner, N., additional, Charles, P., additional, Hamilton, B., additional, Chowdhury, M., additional, Ytterberg, J., additional, Potempa, J., additional, Fisher, B., additional, Thiele, G., additional, Mikuls, T., additional, Venables, P., additional, Adebajo, A. O., additional, Mease, P., additional, Gomez-Reino, J. J., additional, Wollenhaupt, J., additional, Hu, C., additional, Stevens, R., additional, Sieper, J., additional, Dougados, M., additional, Van den Bosch, F., additional, Goupille, P., additional, Rathmann, S. S., additional, Pangan, A. L., additional, Maksymowych, W. P., additional, Brown, M. A., additional, Elewaut, D., additional, Anderson, J., additional, Ramasamy, P., additional, O'Rourke, M., additional, Murphy, C., additional, Fitzgerald, O., additional, Jani, M., additional, Moore, S., additional, Mirjafari, H., additional, Macphie, E., additional, Chinoy, H., additional, Rao, C., additional, McLoughlin, Y., additional, and Preeti, S., additional
Published: 2013
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44. THE QUaD GALACTIC PLANE SURVEY. II. A COMPACT SOURCE CATALOG

Author: Culverhouse, T., primary, Ade, P., additional, Bock, J., additional, Bowden, M., additional, Brown, M. L., additional, Cahill, G., additional, Castro, P. G., additional, Church, S., additional, Friedman, R., additional, Ganga, K., additional, Gear, W. K., additional, Gupta, S., additional, Hinderks, J., additional, Kovac, J., additional, Lange, A. E., additional, Leitch, E., additional, Melhuish, S. J., additional, Memari, Y., additional, Murphy, J. A., additional, Orlando, A., additional, Pryke, C., additional, Schwarz, R., additional, O'Sullivan, C., additional, Piccirillo, L., additional, Rajguru, N., additional, Rusholme, B., additional, Taylor, A. N., additional, Thompson, K. L., additional, Turner, A. H., additional, Wu, E. Y. S., additional, and Zemcov, M., additional
Published: 2011
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45. QUaD: A HIGH-RESOLUTION COSMIC MICROWAVE BACKGROUND POLARIMETER

Author: Hinderks, J. R., primary, Ade, P., additional, Bock, J., additional, Bowden, M., additional, Brown, M. L., additional, Cahill, G., additional, Carlstrom, J. E., additional, Castro, P. G., additional, Church, S., additional, Culverhouse, T., additional, Friedman, R., additional, Ganga, K., additional, Gear, W. K., additional, Gupta, S., additional, Harris, J., additional, Haynes, V., additional, Keating, B. G., additional, Kovac, J., additional, Kirby, E., additional, Lange, A. E., additional, Leitch, E., additional, Mallie, O. E., additional, Melhuish, S., additional, Memari, Y., additional, Murphy, A., additional, Orlando, A., additional, Schwarz, R., additional, Sullivan, C. O', additional, Piccirillo, L., additional, Pryke, C., additional, Rajguru, N., additional, Rusholme, B., additional, Taylor, A. N., additional, Thompson, K. L., additional, Tucker, C., additional, Turner, A. H., additional, Wu, E. Y. S., additional, and Zemcov, M., additional
Published: 2009
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46. SECOND AND THIRD SEASON QUaD COSMIC MICROWAVE BACKGROUND TEMPERATURE AND POLARIZATION POWER SPECTRA

Author: Pryke, C., primary, Ade, P., additional, Bock, J., additional, Bowden, M., additional, Brown, M. L., additional, Cahill, G., additional, Castro, P. G., additional, Church, S., additional, Culverhouse, T., additional, Friedman, R., additional, Ganga, K., additional, Gear, W. K., additional, Gupta, S., additional, Hinderks, J., additional, Kovac, J., additional, Lange, A. E., additional, Leitch, E., additional, Melhuish, S. J., additional, Memari, Y., additional, Murphy, J. A., additional, Orlando, A., additional, Schwarz, R., additional, Sullivan, C. O', additional, Piccirillo, L., additional, Rajguru, N., additional, Rusholme, B., additional, Taylor, A. N., additional, Thompson, K. L., additional, Turner, A. H., additional, Wu, E. Y. S., additional, and Zemcov, M., additional
Published: 2009
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47. PARAMETER ESTIMATION FROM IMPROVED MEASUREMENTS OF THE COSMIC MICROWAVE BACKGROUND FROM QUaD.

Author: Gupta, S., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Friedman, R. B., Ganga, K., Gear, W. K., Hinderks, J., Kovac, J., Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., and Orlando, A.
Published: 2010
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48. Improved Measurements of the Temperature and Polarization of the Cosmic Microwave Background from QUaD

Author: Brown, M. L., Ade, P., Bock, J., Bowden, M., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Friedman, R. B., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, John M, Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Sullivan, C. O, Piccirillo, L., Pryke, Clement L., Rajguru, N., Rusholme, B., Schwarz, R., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: cosmic microwave background, cosmological parameters, cosmology: observations, polarization
Abstract: We present an improved analysis of the final data set from the QUaD experiment. Using an improved technique to remove ground contamination, we double the effective sky area and hence increase the precision of our cosmic microwave background (CMB) power spectrum measurements by ~30% versus that previously reported. In addition, we have improved our modeling of the instrument beams and have reduced our absolute calibration uncertainty from 5% to 3.5% in temperature. The robustness of our results is confirmed through extensive jackknife tests, and by way of the agreement that we find between our two fully independent analysis pipelines. For the standard six-parameter ΛCDM model, the addition of QUaD data marginally improves the constraints on a number of cosmological parameters over those obtained from the WMAP experiment alone. The impact of QUaD data is significantly greater for a model extended to include either a running in the scalar spectral index, or a possible tensor component, or both. Adding both the QUaD data and the results from the Arcminute Cosmology Bolometer Array Receiver experiment, the uncertainty in the spectral index running is reduced by ~25% compared to WMAP alone, while the upper limit on the tensor-to-scalar ratio is reduced from r < 0.48 to r < 0.33 (95% c.l.). This is the strongest limit on tensors to date from the CMB alone. We also use our polarization measurements to place constraints on parity-violating interactions to the surface of last scattering, constraining the energy scale of Lorentz violating interactions to <1.5 × 10–43 GeV (68% c.l.). Finally, we place a robust upper limit on the strength of the lensing B-mode signal. Assuming a single flat band power between ℓ = 200 and ℓ = 2000, we constrain the amplitude of B-modes to be <0.57 μK2 (95% c.l.)., Astronomy
Published: 2009
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49. Cosmological Parameters From the Quad Cmb Polarization Experiment

Author: Castro, P. G., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Church, S., Culverhouse, T., Friedman, R. B., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, John M, Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., Pryke, Clement L., Schwarz, R., O, C., Piccirillo, L., Rajguru, N., Rusholme, B., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: cosmic microwave background, cosmological parameters, methods: statistical, polarization
Abstract: In this paper, we present a parameter estimation analysis of the polarization and temperature power spectra from the second and third season of observations with the QUaD experiment. QUaD has for the first time detected multiple acoustic peaks in the E-mode polarization spectrum with high significance. Although QUaD-only parameter constraints are not competitive with previous results for the standard six-parameter ΛCDM cosmology, they do allow meaningful polarization-only parameter analyses for the first time. In a standard six-parameter ΛCDM analysis, we find the QUaD TT power spectrum to be in good agreement with previous results. However, the QUaD polarization data show some tension with ΛCDM. The origin of this 1σ–2σ tension remains unclear, and may point to new physics, residual systematics, or simple random chance. We also combine QUaD with the five-year WMAP data set and the SDSS luminous red galaxies 4th data release power spectrum, and extend our analysis to constrain individual isocurvature mode fractions, constraining cold dark matter density, αcdmi < 0.11 (95% confidence limit (CL)), neutrino density, αndi < 0.26 (95% CL), and neutrino velocity, αnvi < 0.23 (95% CL), modes. Our analysis sets a benchmark for future polarization experiments., Astronomy
Published: 2009
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50. Small angular scale measurements of the cosmic microwave background temperature power spectrum from QUaD

Author: Friedman, R. B., Ade, P., Bock, J., Bowden, M., Brown, M. L., Cahill, G., Castro, P. G., Church, S., Culverhouse, T., Ganga, K., Gear, W. K., Gupta, S., Hinderks, J., Kovac, John M, Lange, A. E., Leitch, E., Melhuish, S. J., Memari, Y., Murphy, J. A., Orlando, A., O'Sullivan, C., Piccirillo, L., Pryke, Clement L., Rajguru, N., Rusholme, B., Schwarz, R., Taylor, A. N., Thompson, K. L., Turner, A. H., Wu, E. Y. S., and Zemcov, M.
Subjects: cosmic microwave background, cosmology: observations
Abstract: We present measurements of the cosmic microwave background (CMB) radiation temperature anisotropy in the multipole range 2000 << 3000 from the QUaD telescope’s second and third observing seasons. After masking the brightest point sources our results are consistent with the primary ΛCDM expectation alone. We estimate the contribution of residual (un-masked) radio point sources using a model calibrated to our own bright source observations, and a full simulation of the source finding and masking procedure. Including this contribution slightly improves the χ2. We also fit a standard Sunyaev–Zel’dovich (SZ) template to the bandpowers and see no strong evidence of an SZ contribution, which is as expected for σ8 ≈ 0.8., Astronomy
Published: 2009
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