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197 results on '"Harris, S.E."'

1. SNAP telescope

Author

Lampton, Michael L., Akerlof, C.W., Aldering, G., Amanullah, R., Astier, P., Barrelet, E., Bebek, C., Bergstrom, L., Bercovitz, J., Bernstein, G., Bester, M., Bonissent, A., Bower, C., Carithers Jr., W.C., Commins, E.D., Day, C., Deustua, S.E., DiGennaro, R., Ealet, A., Ellis, R.S., Eriksson, M., Fruchter, A., Genat, J.-F., Goldhaber, G., Goobar, A., Groom, D., Harris, S.E., Harvey, P.R., Heetderks, H.D., Holland, S.E., Huterer, D., Karcher, A., Kim, A.G., Kolbe, W., Krieger, B., Lafever, R., Lamoureux, J., Levi, M.E., Levin, D.S., Linder, E.V., Loken, S.C., Malina, R., Massey, R., McKay, T., McKee, S.P., Miquel, R., Mortsell, E., Mostek, N., Mufson, S., Musser, J., Nugent, P., Oluseyi, H., Pain, R., Palaio, N., Pankow, D., Perlmutter, S., Pratt, R., Prieto, E., Refregier, A., Rhodes, J., Robinson, K., Roe, N., Sholl, M., Schubnell, M., Smadja, G., Smoot, G., Spadafora, A., Tarle, G., Tomasch, A., von der Lippe, H., Vincent, R., Walder, J.-P., and Wang, G.

Subjects
Classical and quantum mechanics, general physics
Published
2002

2. Overview of the SuperNova/Acceleration probe (SNAP)

Author

Aldering, Gregory L., Akerlof, C.W., Amanullah, R., Astier, P., Barrelet, E., Bebek, C., Bergstrom, L., Bercovitz, J., Bernstein, G.M., Bester, M., Bonissent, A., Bower, C.R., Carithers Jr., W.C., Commins, E.D., Day, C., Deustua, S.E., DiGennaro, R., Ealet, A., Ellis, R.S., Eriksson, M., Fruchter, A., Genat, J-F., Goldhaber, G., Goobar, A., Groom, D., Harris, S.E., Harvey, P.R.D, Heetderks, H.D., Holland, S.E., Huterer, D., Karcher, A., Kim, A.G., Kolbe, W., Krieger, B., Lafever, R., Lamoureux, J., Lampton, M.L., Levi, M.E., Levin, D.S., Linder, E.V., Loken, S.C., Malina, R., Massey, R., McKay, T., McKee, S.P., Miquel, R., Mortsell, E., Mostek, N., Mufson, S., Musser, J.A., Nugent, P.E., Oluseyi, H., Pain, R., Palaio, N., Pankow, D.H., Perlmutter, S., Pratt, R., Prieto, E., Refregier, A., Rhodes, J., Robinson, K.E., Roe, N., Sholl, M., Schubnell, M., Smadja, G., Smoot, G., Spadafora, A., Tarle, G., Tomasch, A., von der Lippe, H., Vincent, D., Walder, J., and Wang, G.

Subjects
Classical and quantum mechanics, general physics
Published
2002

3. An integral field spectrograph for SNAP supernova studies

Author

Ealet, Anne, Prieto, E., Bonissent, A., Malina, R., Basa, S., LeFevre, O., Mazure, A., Tarle, G., Akerlof, C.W., Aldering, G., Amidei, D.E., Astier, P., Baden, A.R., Bebek, C., Bergstrom, L., Bernstein, G.M., Bower, C.R., Campbell, M., Carithers Jr., W.C., Commins, E.D., Curtis, D.W., Deustua, S.E., Edwards, W.R., Ellis, R.S., Fruchter, A., Frye, B.L., Genat, J., Goldhaber, G., Goobar, A., Goodman, J.A., Graham, J.R., Hardin, D., Harris, S.E., Harvey, P.R., Heetderks, H.D., Honeycutt, R., Holland, S.E., Hook, I., Huterer, D., Kasen, D.N., Kim, A.G., Knop, R.A., Lafever, R., Lampton, M.L., Levi, M.E., Levin, D.S., Levy, J.M., Lidman, C., Lin, R.P., Linder, E.V., Loken, S.C., McKay, T., McKee, S.P., Metzger, M.R., Miquel, R., Mourao, A., Mufson, S., Musser, J.A., Nugent, P.E., Pain, R., Pankow, D.H., Pennypacker, C.R., Perlmutter, S., Refregier, A., Rich, J., Robinson, K.E., Schahmaneche, K., Schubnell, M.S., Spadafora, A., Smoot, G.F., Sullivan, G.W., Tomasch, A.D., and SNAP Collaboration

Subjects
Classical and quantum mechanics, general physics
Published
2002

4. SNAP focal plane

Author

Lampton, Michael L., Kim, A., Akerlof, C.W., Aldering, G., Amanullah, R., Astier, P., Barrelet, E., Bebek, C., Bergstrom, L., Berkovitz, J., Bernstein, G., Bester, M., Bonissent, A., Bower, C., Carithers Jr., W.C., Commins, E.D., Day, C., Deustua, S.E., DiGennaro, R., Ealet, A., Ellis, R.S., Eriksson, M., Fruchter, A., Genat, J.-F., Goldhaber, G., Goobar, A., Groom, D., Harris, S.E., Harvey, P.R., Heetderks, H.D., Holland, S.E., Huterer, D., Karcher, A., Kolbe, W., Krieger, B., Lafever, R., Lamoureux, J., Levi, M.E., Levin, D.S., Linder, E.V., Loken, S.C., Malina, R., Massey, R., McKay, T., McKee, S.P., Miquel, R., Mortsell, E., Mostek, N., Mufson, S., Musser, J., Nugent, P., Oluseyi, H., Pain, R., Palaio, N., Pankow, D., Perlmutter, S., Pratt, R., Prieto, E., Refregier, A., Rhodes, J., Robinson, K., Roe, N., Sholl, M., Schubnell, M., Smadja, G., Smoot, G., Spadafora, A., Tarle, G., Tomasch, A., von der Lippe, H., Vincent, R., Walder, J.-P., and Wang, G.

Subjects
Classical and quantum mechanics, general physics
Published
2002

5. Wide-field surveys from the SNAP mission

Author

Kim, Alex G., Akerlof, C.W., Aldering, G., Amanullah, R., Astier, P., Barrelet, E., Bebek, C., Bergstrom, L., Bercovitz, J., Bernstein, G., Bester, M., Bonissent, A., Bower, C., Carithers Jr., W.C., Commins, E.D., Day, C., Deustua, S.E., DiGennaro, R., Ealet, A., Ellis, R.S., Eriksson, M., Fruchter, A., Genat, J.-F., Goldhaber, G., Goobar, A., Groom, D., Harris, S.E., Harvey, P.R., Heetderks, H.D., Holland, S.E., Huterer, D., Karcher, A., Kolbe, W., Krieger, B., Lafever, R., Lamoureux, J., Levi, M.E., Levin, D.S., Linder, E.V., Loken, S.C., Malina, R., Massey, R., McKay, T., McKee, S.P., Miquel, R., Mortsell, E., Mostek, N., Mufson, S., Musser, J., Nugent, P., Oluseyi, H., Pain, R., Palaio, N., Pankow, D., Perlmutter, S., Pratt, R., Prieto, E., Refregier, A., Rhodes, J., Robinson, K., Roe, N., Sholl, M., Schubnell, M., Smadja, G., Smoot, G., Spadafora, A., Tarle, G., Tomasch, A., von der Lippe, H., Vincent, R., Walder, J.-P., and Wang, G.

Subjects
Physics of elementary particles and fields
Published
2002

6. Anātmavāda

Author

Harris, S.E., Goetz, S., and Taliaferro, C.

Published
2021

8. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author

Ahluwalia, T.S., Prins, B.P., Abdollahi, M., Armstrong, N.J., Aslibekyan, S., Bain, L., Jefferis, B., Baumert, J., Beekman, M., Ben-Shlomo, Y., Bis, J.C., Mitchell, B.D., Geus, E. de, Delgado, G.E., Marek, D., Eriksson, J., Kajantie, E., Kanoni, S., Kemp, J.P., Lu, C., Marioni, R.E., McLachlan, S., Milaneschi, Y., Nolte, I.M., Petrelis, A.M., Porcu, E., Sabater-Lleal, M., Naderi, E., Seppala, I., Shah, T., Singhal, G., Standl, M., Teumer, A., Thalamuthu, A., Thiering, E., Trompet, S., Ballantyne, C.M., Benjamin, E.J., Casas, J.P., Toben, C., Dedoussis, G., Deelen, J., Durda, P., Engmann, J., Feitosa, M.F., Grallert, H., Hammarstedt, A., Harris, S.E., Homuth, G., Hottenga, J.J., Jalkanen, S., Jamshidi, Y., Jawahar, M.C., Jess, T., Kivimaki, M., Kleber, M.E., Lahti, J., Liu, Y., Marques-Vidal, P., Mellstrom, D., Mooijaart, S.P., Muller-Nurasyid, M., Penninx, B., Revez, J.A., Rossing, P., Raikkonen, K., Sattar, N., Scharnagl, H., Sennblad, B., Silveira, A., St Pourcain, B., Timpson, N.J., Trollor, J., Dongen, J. van, Heemst, D. van, Visvikis-Siest, S., Vollenweider, P., Volker, U., Waldenberger, M., Willemsen, G., Zabaneh, D., Morris, R.W., Arnett, D.K., Baune, B.T., Boomsma, D.I., Chang, Y.P.C., Deary, I.J., Deloukas, P., Eriksson, J.G., Evans, D.M., Ferreira, M.A., Gaunt, T., Gudnason, V., Hamsten, A., Heinrich, J., Hingorani, A., Humphries, S.E., Jukema, J.W., Koenig, W., Kumari, M., Kutalik, Z., Lawlor, D.A., Lehtimaki, T., Marz, W., Mather, K.A., Naitza, S., Nauck, M., Ohlsson, C., Price, J.F., Raitakari, O., Rice, K., Sachdev, P.S., Slagboom, E., Sorensen, T.I.A., Spector, T., Stacey, D., Stathopoulou, M.G., Tanaka, T., Wannamethee, S.G., Whincup, P., Rotter, J.I., Dehghan, A., Boerwinkle, E., Psaty, B.M., Snieder, H., Alizadeh, B.Z., and CHARGE Inflammation Working Grp

Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Published
2021

11. X-ray and optical wave mixing

Author

Glover, T.E., Fritz, D.M., Cammarata, M., Allison, T.K., Con, Sinisa, Feldkamp, J.M., Lemke, H., Zhu, D., Feng, Y., Coffee, R.N., Fuchs, M., Ghimire, S., Chen, J., Shwartz, S., Reis, D.A., Harris, S.E., and Hastings, J.B.

Subjects
Oscillatory reactions -- Research, X-rays -- Usage, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Light-matter interactions are ubiquitous, and underpin a wide range of basic research fields and applied technologies. Although optical interactions have been intensively studied, their microscopic details are often poorly understood and have so far not been directly measurable. X-ray and optical wave mixing was proposed nearly half a century ago as an atomic-scale probe of optical interactions but has not yet been observed owing to a lack of sufficiently intense X-ray sources. Here we use an X-ray laser to demonstrate X-ray and optical sum-frequency generation. The underlying nonlinearity is a reciprocal-space probe of the optically induced charges and associated microscopic fields that arise in an illuminated material. To within the experimental errors, the measured efficiency is consistent with first- principles calculations of microscopic optical polarization in diamond. The ability to probe optical interactions on the atomic scale offers new opportunities in both basic and applied areas of science., Light-matter interactions have advanced our understanding of atoms, molecules and materials, and are also central to a number of areas of applied science. Although optical interactions have received a great [...]

Published
2012
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12. Light speed reduction to 17 metres per second in an ultracold atomic gas

Author

Vestergaard Hau, Lene, Harris, S.E., Dutton, Zachary, and Behroozi, Cyrus H.

Subjects
Superconducting quantum interference devices -- Observations, Light -- Speed, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Electromagnetically induced transparency allows the propagation of light pulses through opaque medium. This has been demonstrated in an ultracold gas of sodium atoms where optical pulses propagate 20 million times slower than the speed of light in a vacuum. An inferred nonlinear refractive index of 0.18 squared cm W(super-1) is reported, and large optical nolinearities are exhibited.

Published
1999

13. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018)

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., Lee, S.J. van der, Ware, E.B., Windham, B.G., Wright, M.J., Yang, J.Y., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Bohmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kahonen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Hellard, S. le, Lee, T., Lehtimaki, T., Li, S.C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikainen, L.P., Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumare, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., Jager, P.L. de, Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hagg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Raikkonen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., Duijn, C.M. van, Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Published
2019

14. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (Nature Communications, (2018), 9, 1, (2098), 10.1038/s41467-018-04362-x)

Author

Davies, G. Lam, M. Harris, S.E. Trampush, J.W. Luciano, M. Hill, W.D. Hagenaars, S.P. Ritchie, S.J. Marioni, R.E. Fawns-Ritchie, C. Liewald, D.C.M. Okely, J.A. Ahola-Olli, A.V. Barnes, C.L.K. Bertram, L. Bis, J.C. Burdick, K.E. Christoforou, A. DeRosse, P. Djurovic, S. Espeseth, T. Giakoumaki, S. Giddaluru, S. Gustavson, D.E. Hayward, C. Hofer, E. Ikram, M.A. Karlsson, R. Knowles, E. Lahti, J. Leber, M. Li, S. Mather, K.A. Melle, I. Morris, D. Oldmeadow, C. Palviainen, T. Payton, A. Pazoki, R. Petrovic, K. Reynolds, C.A. Sargurupremraj, M. Scholz, M. Smith, J.A. Smith, A.V. Terzikhan, N. Thalamuthu, A. Trompet, S. van der Lee, S.J. Ware, E.B. Windham, B.G. Wright, M.J. Yang, J. Yu, J. Ames, D. Amin, N. Amouyel, P. Andreassen, O.A. Armstrong, N.J. Assareh, A.A. Attia, J.R. Attix, D. Avramopoulos, D. Bennett, D.A. Böhmer, A.C. Boyle, P.A. Brodaty, H. Campbell, H. Cannon, T.D. Cirulli, E.T. Congdon, E. Conley, E.D. Corley, J. Cox, S.R. Dale, A.M. Dehghan, A. Dick, D. Dickinson, D. Eriksson, J.G. Evangelou, E. Faul, J.D. Ford, I. Freimer, N.A. Gao, H. Giegling, I. Gillespie, N.A. Gordon, S.D. Gottesman, R.F. Griswold, M.E. Gudnason, V. Harris, T.B. Hartmann, A.M. Hatzimanolis, A. Heiss, G. Holliday, E.G. Joshi, P.K. Kähönen, M. Kardia, S.L.R. Karlsson, I. Kleineidam, L. Knopman, D.S. Kochan, N.A. Konte, B. Kwok, J.B. Le Hellard, S. Lee, T. Lehtimäki, T. Li, S.-C. Lill, C.M. Liu, T. Koini, M. London, E. Longstreth, W.T., Jr. Lopez, O.L. Loukola, A. Luck, T. Lundervold, A.J. Lundquist, A. Lyytikäinen, L.-P. Martin, N.G. Montgomery, G.W. Murray, A.D. Need, A.C. Noordam, R. Nyberg, L. Ollier, W. Papenberg, G. Pattie, A. Polasek, O. Poldrack, R.A. Psaty, B.M. Reppermund, S. Riedel-Heller, S.G. Rose, R.J. Rotter, J.I. Roussos, P. Rovio, S.P. Saba, Y. Sabb, F.W. Sachdev, P.S. Satizabal, C.L. Schmid, M. Scott, R.J. Scult, M.A. Simino, J. Slagboom, P.E. Smyrnis, N. Soumaré, A. Stefanis, N.C. Stott, D.J. Straub, R.E. Sundet, K. Taylor, A.M. Taylor, K.D. Tzoulaki, I. Tzourio, C. Uitterlinden, A. Vitart, V. Voineskos, A.N. Kaprio, J. Wagner, M. Wagner, H. Weinhold, L. Wen, K.H. Widen, E. Yang, Q. Zhao, W. Adams, H.H.H. Arking, D.E. Bilder, R.M. Bitsios, P. Boerwinkle, E. Chiba-Falek, O. Corvin, A. De Jager, P.L. Debette, S. Donohoe, G. Elliott, P. Fitzpatrick, A.L. Gill, M. Glahn, D.C. Hägg, S. Hansell, N.K. Hariri, A.R. Ikram, M.K. Jukema, J.W. Vuoksimaa, E. Keller, M.C. Kremen, W.S. Launer, L. Lindenberger, U. Palotie, A. Pedersen, N.L. Pendleton, N. Porteous, D.J. Räikkönen, K. Raitakari, O.T. Ramirez, A. Reinvang, I. Rudan, I. Dan Rujescu Schmidt, R. Schmidt, H. Schofield, P.W. Schofield, P.R. Starr, J.M. Steen, V.M. Trollor, J.N. Turner, S.T. Van Duijn, C.M. Villringer, A. Weinberger, D.R. Weir, D.R. Wilson, J.F. Malhotra, A. McIntosh, A.M. Gale, C.R. Seshadri, S. Mosley, T.H., Jr. Bressler, J. Lencz, T. Deary, I.J.

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article. © 2019, The Author(s).

Published
2019

15. Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Author

Harris, S.E., Corley, J., Wojczynski, M.K., Nauck, M., Levy, D., Gu, C., Sorensen, T.I.A., Noordam, R., Guo, X., Hill, W.D., Chen, Y.-D.I., Liu, C., Yao, J., Kraja, A.T., Daw, E.W., Irvin, M.R., Christensen, C., Newman, A.B., Hansen, T., Hudson, G., Zeng, D., Wu, H., Uitterlinden, A.G., Wareham, N.J., Perls, T.T., Grarup, N., Broeckel, U., Luan, J., Fu, M., Hemani, G., de Mutsert, R., Lin, S.J., Wilson, J.G., Jorgensen, M.E., Witte, D.R., Have, C.T., Ribel-Madsen, R., Wang, Y., Love-Gregory, L.D., Bowden, D.W., Province, M.A., Rotter, J.I., Taylor, A.M., Hunt, S.C., Thyagarajan, B., Goodarzi, M.O., Ridker, P.M., Torp-Pedersen, C., Ligthart, S., Starr, J.M., Feitosa, M.F., Arnett, D.K., de Haan, H.G., Jorgensen, T., Weeke, P.E., Graff, M., de las Fuentes, L., Justice, A.E., Hayward, C., Kerrison, N.D., Pedersen, O., Bonnelykke, K., Perry, J.A., Fetterman, J.L., Hai, Y., Malik, A.N., Vestergaard, H., Cropp, C.D., Ryan, K.A., Christensen, K., The Population Sciences Branch, NHLBI/NIH, Armasu, S.M., Langenberg, C., Forouhi, N.G., Yang, W., Teumer, A., Rodriguez, S., Kardia, S.L.R., Qi, Q., Becker, D.M., Baranski, T.J., Yanek, L.R., Rao, D.C., Fernandez, E.P., Lin, K.-H., Li-Gao, R., Sofer, T., Nohr, E.A., Larson, N.B., Sheu, W.H.-H., Elliott, P., An, P., Schnurr, T.M., Gu, Z., Taylor, K.D., Davies, G., Kilpelainen, T.O., Lee, W.-J., Patki, A., Barve, R.A., Brandslund, I., Sandow, K., Weiss, S., Wang, L., Stergiakouli, E., Mathias, R.A., Ghanbari, M., Tiwari, H.K., Rivadeneira, F., Davila-Roman, V.G., de Andrade, M., North, K.E., Richardson, T.G., Horta, B.L., Bielinski, S.J., Linneberg, A., Young, K., Argos, M., Dehghan, A., Chasman, D.I., Mook-Kanamori, D.O., Vaidya, D., Petersmann, A., Scott, R.A., Meigs, J.B., Ahluwalia, T.S., Gao, H., Rosendaal, F.R., Chakravarti, A., van Heemst, D., Cox, S.R., Williams, C., Pankow, J., Giulianini, F., Weir, B.S., Jonsson, A.E., Hartwig, F.P., Rohde, R., Ikram, M.A., Homuth, G., Lee, J.H., Deary, I.J., Erzurumluoglu, A.M., Chu, A.Y., Emery, L.S., Franco, O.H., Ong, K.K., Arking, D.E., Loos, R.J.F., Tzoulaki, I., Pattie, A., Timpson, N.J., and Turner, S.T.

Abstract

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E−04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E−03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E−06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

Published
2019
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16. Differential roles for bone morphogenetic protein (BMP) receptor type IB and IA in differentiation and specification of mesenchymal precursor cells to osteoblast and adipocyte lineages

Author

Chen, D., Ji, X., Harris, M.A., Feng, J.Q., Karsenty, G., Celeste, A.J., Rosen, V., Mundy, G.R., and Harris, S.E.

Subjects
Proteins -- Research, Osteoblasts -- Research, Fat cells -- Research, Cell differentiation -- Research, Morphogenesis -- Research, Biological sciences
Abstract

A study was conducted to determine the roles of type IA and IB bone morphogenetic proteins (BMP) receptors during osteoblast and adipocyte differentiation using 2T3 cells that were derived from the calvaria of transgenic mouse expressing T antigen. The overexpression of the type IA and IB BMP receptors caused 2T3 cells to differentiate into different phenotypes. This suggested that type IA and IB BMP receptors mediate different signals responsible for alternate paths of differentiation.

Published
1998

22. Promising Across Lives to Save Non-Existent Beings: Identity, Rebirth and the Bodhisattva’s Vow

Author

Harris, S.E.

Subjects
Philosophy, Aesthetics, Bodhisattva, Mahayana buddhism, media_common.quotation_subject, Personal identity, Buddhism, Identity (social science), Social psychology, media_common
Abstract

This essay considers whether the common practice within Buddhist texts of ascribing identity across lives is consistent with the lack of physical and continuity between lives, as well as the related question of whether the vow of the Bodhisattva to liberate all sentient beings can be viewed as a personal multi-lifetime commitment.

Published
2018

24. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475,000 Individuals

Author

Chasman, D.I., Herzig, K.-H., Laakso, M., Kraja, A.T., Padmanabhan, S., Amin, N., Marioni, R.E., Giulianini, F., Havulinna, A.S., Asselbergs, F.W., Stafford, J.M., Stirrups, K.E., Fornage, M., Danesh, J., Lindgren, C.M., Bonnycastle, L.L., Zhang, H., Groop, L., Loos, R.J.F., J��rgensen, M.E., Christensen, C.K., CHD Exome+, Rudan, I., Butterworth, A.S., Cook, J.P., Liu, Y., Morrison, A.C., Guo, X., Barnes, M.R., Fava, C., Province, M.A., K��r��j��m��ki, A., Wareham, N.J., Deary, I.J., CHARGE EXOME BP, Edwards, T.L., Poveda, A., Kooperberg, C., Have, C.T., Ingelsson, E., Wain, L.V., Rotter, J.I., Levy, D., Tragante, V., Young, R., Cabrera, C.P., Connell, J.M., Caulfield, M.J., Little, L., Jarvelin, M.-R., Warren, H.R., Zhang, W., Rayner, N.W., Gambaro, G., Munroe, P.B., Ferreira, T., Morris, A.P., Farmaki, A.-E., Smith, A.V., Pedersen, O., Esko, T., Heikki, O., Bork-Jensen, J., Witte, D.R., Drenos, F., Southam, L., Deloukas, P., Franceschini, N., Zeggini, E., Lind, L., Van Der Harst, P., Riaz, M., Rice, K., Grarup, N., Dominiczak, A.F., Vergnaud, A.-C., Hayward, C., Ehret, G.B., Melander, O., Tzoulaki, I., Boerwinkle, E., Evangelou, E., Wilson, J.G., Polasek, O., Harris, S.E., Tuomilehto, J., Franks, P.W., McCarthy, M.I., Skaaby, T., D��rr, M., Poulter, N.R., Salomaa, V., Finland, Willer, C.J., Saleheen, D., The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group, Lakka, T.A., Newton-Cheh, C., Kooner, J.S., Exome BP, Samani, N.J., Van Der Meer, P., Kardia, S.L.R., Gao, H., Mei, H., Surendran, P., Van Duijn, C.M., Richard, M.A., Gudnason, V., Smith, J.A., Boehnke, M., Varga, T.V., Hansen, T., M��gi, R., Chambers, J.C., Mahajan, A., Rauramaa, R., Tuomi, T., Yiorkas, A.M., Psaty, B.M., Dedoussis, G., Brandslund, I., Sever, P.J., Mohlke, K.L., Weiss, S., Liu, C., Langenberg, C., De Boer, R.A., Blakemore, A.I.F., Grove, M.L., Malerba, G., Karpe, F., Lu, Y., Joehanes, R., Stan����kov��, A., Manning, A.K., Sim, X., Ridker, P.M., Starr, J.M., Hallmans, G., Elliott, P., Howson, J.M.M., GoT2D:T2DGenes Consortia, Palmer, C.N.A., Linneberg, A., Palmas, W., Menni, C., and Giri, A.

Abstract

Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results - Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ���475 000), and the other in the subset of individuals of European descent (���423 000). Twenty-one SNVs were genome-wide significant (P

Published
2017
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25. Buddhism and disability

Author

Harris, S.E., Schumm, D.Y., Stoltzfus, M., Schumm, D.Y., and Stoltzfus, M.

Published
2016

26. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

Author

Davies, G., Marioni, R.E., Liewald, D.C., Hill, W.D., Hagenaars, S.P., Harris, S.E., Ritchie, S.J., Luciano, M., Fawns-Ritchie, C., Lyall, D., Cullen, B., Cox, S.R., Hayward, C., Porteous, D.J., Evans, J., McIntosh, A.M., Gallacher, J., Craddock, N., Pell, J.P., Smith, D.J., Gale, C.R., and Deary, I.J.

Abstract

People’s differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal–numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in theATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31%(s.e.m.=1.8%) for verbal–numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer’s disease and schizophrenia.

Published
2016

27. Pleiotropy between neuroticism and physical and mental health: findings from 108038 men and women in UK Biobank

Author

Gale, C.R., Hagenaars, S.P., Davies, G., Hill, W.D., Liewald, D.C.M., Cullen, B., Penninx, B.W., CHARGE consortium Aging & Longevity Group, [Unknown], Boomsma, D.I., Pell, J., McIntosh, A.M., Smith, D.J., Deary, I.J., and Harris, S.E.

Subjects
mental disorders
Abstract

People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108?038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (? between 0.009-0.043), and in a negative direction in the case of body mass index (?=-0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.

Published
2016

28. Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N = 112 151) and 24 GWAS consortia

Author

Hagenaars, S.P., Harris, S.E., Davies, G., Hill, W.D., Liewald, D.C.M., Ritchie, S. J., Marioni, R.E., Fawns-Ritchie, C., Cullen, B., Malik, R., Worrall, B.B., Sudlow, C.L.M., Wardlaw, J.M., Gallacher, J., Pell, J., McIntosh, A.M., Smith, D.J., Gale, C.R., and Deary, I.J.

Abstract

The causes of the known associations between poorer cognitive function and many adverse neuropsychiatric outcomes, poorer physical health, and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric, and cognitive traits in the participants of UK Biobank, a very large population-based sample (N = 112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics applied to the method of linkage disequilibrium regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, BMI, intracranial volume, infant head circumference, and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.

Published
2016

31. Improving Phenotypic Prediction by Combining Genetic and Epigenetic Associations

Author

Shah, S., Bonder, M.J., Marioni, R.E., Zhu, Z.H., McRae, A.F., Zhernakova, A., Harris, S.E., Liewald, D., Henders, A.K., Mendelson, M.M., Liu, C.Y., Joehanes, R., Liang, L.M., Levy, D., Martin, N.G., Starr, J.M., Wijmenga, C., Wray, N.R., Yang, J., Montgomery, G.W., Franke, L., Deary, I.J., Visscher, P.M., and BIOS Consortium

Published
2015

32. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Author

Davies, G., Armstrong, N., Bis, J.C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C.A., Kirin, M., Lahti, J., Lee, S.J. van der, Hellard, S. le, Liu, T., Marioni, R.E., Oldmeadow, C., Postmus, I., Smith, A.V., Smith, J.A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S.E., Hill, W.D., Liewald, D.C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A.A., Au, R., Becker, J.T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B.M., Campbell, H., Corley, J., Jager, P.L. de, Dufouil, C., Eriksson, J.G., Espeseth, T., Faul, J.D., Ford, I., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Heiss, G., Hofman, A., Holliday, E.G., Huffman, J., Kardia, S.L.R., Kochan, N., Knopman, D.S., Kwok, J.B., Lambert, J.C., Lee, T., Li, G., Li, S.C., Loitfelder, M., Lopez, O.L., Lundervold, A.J., Lundqvist, A., Mather, K.A., Mirza, S.S., Nyberg, L., Oostra, B.A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B.M., Redmond, P., Reppermund, S., Rotter, J.I., Schmidt, H., Schuur, M., Schofield, P.W., Scott, R.J., Steen, V.M., Stott, D.J., Swieten, J.C. van, Taylor, K.D., Trollor, J., Trompet, S., Uitterlinden, A.G., Weinstein, G., Widen, E., Windham, B.G., Jukema, J.W., Wright, A.F., Wright, M.J., Yang, Q., Amieva, H., Attia, J.R., Bennett, D.A., Brodaty, H., Craen, A.J.M. de, Hayward, C., Ikram, M.A., Lindenberger, U., Nilsson, L.G., Porteous, D.J., Raikkonen, K., Reinvang, I., Rudan, I., Sachdev, P.S., Schmidt, R., Schofield, P.R., Srikanth, V., Starr, J.M., Turner, S.T., Weir, D.R., Wilson, J.F., Duijn, C. van, Launer, L., Fitzpatrick, A.L., Seshadri, S., Jr, T.H.M., Deary, I.J., and Generation Scotland

Subjects
Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 [VDP], Social sciences: 200::Psychology: 260::Cognitive psychology: 267 [VDP], Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714 [VDP], Samfunnsvitenskap: 200::Psykologi: 260::Kognitiv psykologi: 267 [VDP]
Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer’s disease: TOMM40, APOE, ABCG1 and MEF2C. publishedVersion

Published
2015

36. VISUAL AND ACOUSTIC SIGNALLING IN THE MUSICAL FIDDLER CRAB (UCA MUSICA) FROM WESTERN MEXICO

Author

Harris, S.E., Woodward, D.M., Fontaine, J.L., and Barnwell, F.H.

Subjects
Zoological research -- Analysis, Sound production by animals -- Analysis, Fiddler-crabs -- Psychological aspects
Abstract

Uca musica males possess a stridulatory apparatus consisting of ridges on the underside of the major cheliped and an opposable row of tubercles on the face of the first walking leg. We recorded sounds from a crab under lab conditions and filmed and videotaped waving displays of males at San Bias and Manzanillo. Means for individual sounds (N=20) during a sustained series were: duration, 0.79 s; number of pulses per sound, 25; pulse repetition rate, 31.6 per s. Pulses were sharply defined at the beginning of a sound but became more complex as, presumably, the stridulatory surfaces of the cheliped and walking leg were engaged. Waving displays resembled those in U. terpsichores, switching from a low intensity lateral circular motion of the large claw (averaging 1.6 s from start to finish) to a high intensity series of rapid (2.6 per s) downward thrusts of the forward-directed chelipeds when females approached the burrow entrance of the male.

Published
1998

37. Are APOE ɛ genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?

Author

Lyall, D.M., Harris, S.E., Bastin, M.E., Muñoz Maniega, S., Murray, C., Lutz, M.W., Saunders, A.M., Roses, A.D., Valdés Hernández, M. del C., Royle, N.A., Starr, J.M., Porteous, D.J., Wardlaw, J.M., and Deary, I.J.

Subjects
ALZHEIMERS-DISEASE, AGE, ONSET, MEMORY, INFANTS, TRACTOGRAPHY, PERFORMANCE, BIRTH COHORT 1936, POLYMORPHISM
Abstract

Genetic polymorphisms in the APOE ε and TOMM40 ‘523’ poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer’s disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE ε2/ε3/ε4 status and TOMM40 523 poly-T repeat length. Data were available from 758–814 subjects for cognitive analysis, and 522–543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all

Published
2014

38. Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

Author

Sabater-Lleal, M., Huang, J., Chasman, D., Naitza, S., Dehghan, A., Johnson, A.D., Teumer, A., Reiner, A.P., Folkersen, L., Basu, S., Rudnicka, A.R., Trompet, S., Malarstig, A., Baumert, J., Bis, J.C., Guo, X.Q., Hottenga, J.J., Shin, S.Y., Lopez, L.M., Lahti, J., Tanaka, T., Yanek, L.R., Oudot-Mellakh, T., Wilson, J.F., Navarro, P., Huffman, J.E., Zemunik, T., Redline, S., Mehra, R., Pulanic, D., Rudan, I., Wright, A.F., Kolcic, I., Polasek, O., Wild, S.H., Campbell, H., Curb, J.D., Wallace, R., Liu, S.M., Eaton, C.B., Becker, D.M., Becker, L.C., Bandinelli, S., Raikkonen, K., Widen, E., Palotie, A., Fornage, M., Green, D., Gross, M., Davies, G., Harris, S.E., Liewald, D.C., Starr, J.M., Williams, F.M.K., Grant, P.J., Spector, T.D., Strawbridge, R.J., Silveira, A., Sennblad, B., Rivadeneira, F., Uitterlinden, A.G., Franco, O.H., Hofman, A., Dongen, J. van, Willemsen, G., Boomsma, D.I., Yao, J., Jenny, N.S., Haritunians, T., McKnight, B., Lumley, T., Taylor, K.D., Rotter, J.I., Psaty, B.M., Peters, A., Gieger, C., Illig, T., Grotevendt, A., Homuth, G., Volzke, H., Kocher, T., Goel, A., Franzosi, M.G., Seedorf, U., Clarke, R., Steri, M., Tarasov, K.V., Sanna, S., Schlessinger, D., Stott, D.J., Sattar, N., Buckley, B.M., Rumley, A., Lowe, G.D., McArdle, W.L., Chen, M.H., Tofler, G.H., Song, J., Boerwinkle, E., Folsom, A.R., Rose, L.M., Franco-Cereceda, A., Teichert, M., Ikram, M.A., Mosley, T.H., Bevan, S., Dichgans, M., Rothwell, P.M., Sudlow, C.L.M., Hopewell, J.C., Chambers, J.C., Saleheen, D., Kooner, J.S., Danesh, J., Nelson, C.P., Erdmann, J., Reilly, M.P., Kathiresan, S., Schunkert, H., Morange, P.E., Ferrucci, L., Eriksson, J.G., Jacobs, D., Deary, I.J., Soranzo, N., Witteman, J.C.M., Geus, E.J.C. de, Tracy, R.P., Hayward, C., Koenig, W., Cucca, F., Jukema, J.W., Eriksson, P., Seshadri, S., Markus, H.S., Watkins, H., Samani, N.J., Wallaschofski, H., Smith, N.L., Tregouet, D., Ridker, P.M., Tang, W.H., Strachan, D.P., Hamsten, A., O'Donnell, C.J., VTE Consortium, STROKE Consortium, WTCCC2, CD4 Consortium, CARDIoGRAM Consortium, Epidemiology, Cell biology, Urology, Internal Medicine, Immunology, Radiology & Nuclear Medicine, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes

Subjects
Male, Netherlands Twin Register (NTR), Pathology, Myocardial Infarction, Genome-wide association study, Coronary Artery Disease, Disease, VARIANTS, 030204 cardiovascular system & hematology, Fibrinogen, Genome, 0302 clinical medicine, Risk Factors, Genotype, ARTERY-DISEASE, GENE-EXPRESSION, Aged, 80 and over, Genetics, INDIVIDUAL PARTICIPANT METAANALYSIS, 0303 health sciences, Hispanic or Latino, Venous Thromboembolism, Middle Aged, 3. Good health, Stroke, Meta-analysis, Medical genetics, Female, HEALTH, Cardiology and Cardiovascular Medicine, medicine.drug, Adult, medicine.medical_specialty, cardiovascular diseases, fibrinogen, gene expression, genome-wide association study, Adolescent, Implementation Science [NCEBP 3], Black People, Polymorphism, Single Nucleotide, White People, Young Adult, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Physiology (medical), medicine, Humans, CORONARY-HEART-DISEASE, HEMOSTASIS, Genetic Predisposition to Disease, Aged, 030304 developmental biology, business.industry, Heritability, GENOTYPES, MYOCARDIAL-INFARCTION, Genetic Loci, RISK-FACTORS, business
Abstract

Background— Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion ( Methods and Results— We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant ( P −8 ) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. Conclusions— We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.

Published
2013

39. A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability: the HALCyon Programme

Author

Alfred, T., Ben-Shlomo, Y., Cooper, R., Hardy, R., Gaunt, T.R., Gunnell, D., Harris, S.E., Kumari, M., Martin, R.M., Sayer, A.A., Starr, J.M., Kuh, D., Day, I.N.M., and The HALCyon study team

Abstract

Background: Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.\ud \ud Methods :As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.\ud \ud Results: Few important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.\ud \ud Conclusion: Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.

Published
2012

41. Expression and function of Dlx genes in the osteoblast lineage

Author

Li, H., Marijanović, Inga, Kronenberg, M.S., Erceg, I., Stover, M.L., Velonis, D., Mina, M., Heinrich, J.G., Harris, S.E., Upholt, W.B., Kalajzić, Ivo, and Lichtler, A.C.

Subjects
musculoskeletal diseases, Distal-less homeobox proteins, Homeodomain Proteins, RNA, Messenger, Transcription Factors, embryonic structures
Abstract

Our laboratory and others have shown that overexpression of Dlx5 stimulates osteoblast differentiation. Dlx5(-/-)/Dlx6(-/-) mice have more severe craniofacial and limb defects than Dlx5(-/-), some of which are potentially due to defects in osteoblast maturation. We wished to investigate the degree to which other Dlx genes compensate for the lack of Dlx5, thus allowing normal development of the majority of skeletal elements in Dlx5(-/-) mice. Dlx gene expression in cells from different stages of the osteoblast lineage isolated by FACS sorting showed that Dlx2, Dlx5 and Dlx6 are expressed most strongly in less mature osteoblasts, whereas Dlx3 is very highly expressed in differentiated osteoblasts and osteocytes. In situ hybridization and Northern blot analysis demonstrated the presence of endogenous Dlx3 mRNA within osteoblasts and osteocytes. Dlx3 strongly upregulates osteoblastic markers with a potency comparable to Dlx5. Cloned chick or mouse Dlx6 showed stimulatory effects on osteoblast differentiation. Our results suggest that Dlx2 and Dlx6 have the potential to stimulate osteoblastic differentiation and may compensate for the absence of Dlx5 to produce relatively normal osteoblastic differentiation in Dlx5 knockout mice, while Dlx3 may play a distinct role in late stage osteoblast differentiation and osteocyte function.

Published
2008

42. Directional dominance on stature and cognition in diverse human populations

Author

Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., Sotoodehnia, N., Southam, L., Stanton, A.V., Stathopoulou, M.G., Strauch, K., Strawbridge, R.J., Suderman, M.J., Tandon, N., Tang, S.T., Taylor, K.D., Tayo, B.O., Töglhofer, A.M., Tomaszewski, M., T?ernikova N., Tuomilehto, J., Uitterlinden, A.G., Vaidya, D., van Hylckama Vlieg, A., van Setten, J., Vasankari, T., Vedantam, S., Vlachopoulou, E., Vozzi, D., Vuoksimaa, E., Waldenberger, M., Ware, E.B., Wentworth-Shields, W., Whitfield, J.B., Wild, S., Willemsen, G., Yajnik, C.S., Yao, J., Zaza, G., Zhu, X., BioBank Japan, Project, Salem, R.M., Melbye, M., Bisgaard, H., Samani, N.J., Cusi, D., Mackey, D.A., Cooper, R.S., Froguel, P., Pasterkamp, G., Grant, S.F., Hakonarson, H., Ferrucci, L., Scott, R.A., Morris, A.D., Palmer, C.N., Dedoussis, G., Deloukas, P., Bertram, L., Lindenberger, U., Berndt, S.I., Lindgren, C.M., Timpson, N.J., Tönjes, A., Munroe, P.B., Sørensen, T.I., Rotimi, C.N., Arnett, D.K., Oldehinkel, A.J., Kardia, S.L., Balkau, B., Gambaro, G., Morris, A.P., Eriksson, J.G., Wright, M.J., Martin, N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., Wilson, J.F., Immunology, Medical Microbiology & Infectious Diseases, Erasmus MC other, Medical Informatics, Epidemiology, Pathology, Public Health, Ophthalmology, Internal Medicine, Cardiology, Child and Adolescent Psychiatry / Psychology, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Joshi, Peter K, Esko, Tonu, Mattsson, Hannele, Eklund, Niina, Gandin, Ilaria, Nutile, Teresa, Jackson, Anne U., Schurmann, Claudia, Smith, Albert V., Zhang, Weihua, Okada, Yukinori, Stančáková, Alena, Faul, Jessica D., Zhao, Wei, Bartz, Traci M., Concas, MARIA PINA, Franceschini, Nora, Enroth, Stefan, Vitart, Veronique, Trompet, Stella, Guo, Xiuqing, Chasman, Daniel I., O'Connel, Jeffrey R., Corre, Tanguy, Nongmaithem, Suraj S., Chen, Yuning, Mangino, Massimo, Ruggiero, Daniela, Traglia, Michela, Farmaki, Aliki Eleni, Kacprowski, Tim, Bjonnes, Andrew, Van Der Spek, Ashley, Wu, Ying, Giri, Anil K., Yanek, Lisa R., Wang, Lihua, Hofer, Edith, Rietveld, Cornelius A., Mcleod, Olga, Cornelis, Marilyn C., Pattaro, Cristian, Verweij, Niek, Baumbach, Clemen, Abdellaoui, Abdel, Warren, Helen R., Vuckovic, Dragana, Mei, Hao, Bouchard, Claude, Perry, John R. B., Cappellani, Stefania, Mirza, Saira S., Benton, Miles C., Broeckel, Ulrich, Medland, Sarah E., Lind, Penelope A., Malerba, Giovanni, Drong, Alexander, Yengo, Loic, Bielak, Lawrence F., Zhi, Degui, Van Der Most, Peter J., Shriner, Daniel, Mägi, Reedik, Hemani, Gibran, Karaderi, Tugce, Wang, Zhaoming, Liu, Tian, Demuth, Ilja, Zhao, Jing Hua, Meng, Weihua, Lataniotis, Lazaro, Van Der Laan, Sander W., Bradfield, Jonathan P., Wood, Andrew R., Bonnefond, Amelie, Ahluwalia, Tarunveer S., Hall, Leanne M., Salvi, Erika, Yazar, Seyhan, Carstensen, Lisbeth, De Haan, Hugoline G., Abney, Mark, Afzal, Uzma, Allison, Matthew A., Amin, Najaf, Asselbergs, Folkert W., Bakker, Stephan J. L., Barr, R. Graham, Baumeister, Sebastian E., Benjamin, Daniel J., Bergmann, Sven, Boerwinkle, Eric, Bottinger, Erwin P., Campbell, Archie, Chakravarti, Aravinda, Chan, Yingleong, Chanock, Stephen J., Chen, Constance, Chen, Y. D. Ida, Collins, Francis S., Connell, John, Correa, Adolfo, Cupples, L. Adrienne, Smith, George Davey, Davies, Gail, Dörr, Marcu, Ehret, Georg, Ellis, Stephen B., Feenstra, Bjarke, Feitosa, Mary F., Ford, Ian, Fox, Caroline S., Frayling, Timothy M., Friedrich, Nele, Geller, Frank, Scotland, Generation, Gillham Nasenya, Irina, Gottesman, Omri, Graff, Misa, Grodstein, Francine, Gu, Charle, Haley, Chri, Hammond, Christopher J., Harris, Sarah E., Harris, Tamara B., Hastie, Nicholas D., Heard Costa, Nancy L., Heikkilä, Kauko, Hocking, Lynne J., Homuth, Georg, Hottenga, Jouke Jan, Huang, Jinyan, Huffman, Jennifer E., Hysi, Pirro G., Ikram, M. Arfan, Ingelsson, Erik, Joensuu, Anni, Johansson, Åsa, Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kanoni, Stavroula, Kerr, Shona M., Khan, Nazir M., Koellinger, Philipp, Koistinen, Heikki A., Kooner, Manraj K., Kubo, Michiaki, Kuusisto, Johanna, Lahti, Jari, Launer, Lenore J., Lea, Rodney A., Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C. M., Lind, Lar, Loh, Marie, Lokki, Marja Liisa, London, Stephanie J., Loomis, Stephanie J., Loukola, Anu, Lu, Yingchang, Lumley, Thoma, Lundqvist, Annamari, Männistö, Satu, Marques Vidal, Pedro, Masciullo, Corrado, Matchan, Angela, Mathias, Rasika A., Matsuda, Koichi, Meigs, James B., Meisinger, Christa, Meitinger, Thoma, Menni, Cristina, Mentch, Frank D., Mihailov, Evelin, Milani, Lili, Montasser, May E., Montgomery, Grant W., Morrison, Alanna, Myers, Richard H., Nadukuru, Rajiv, Navarro, Pau, Nalis, Mari, Nieminen, Markku S., Nolte, Ilja M., O'Connor, George T., Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Pankow, James S., Patarcic, Inga, Pavani, Francesca, Peyser, Patricia A., Pietilainen, Kirsi, Poulter, Neil, Prokopenko, Inga, Ralhan, Sarju, Redmond, Paul, Rich, Stephen S., Rissanen, Harri, Robino, Antonietta, Rose, Lynda M., Rose, Richard, Sala, Cinzia, Salako, Babatunde, Salomaa, Veikko, Sarin, Antti Pekka, Saxena, Richa, Schmidt, Helena, Scott, Laura J., Scott, William R., Sennblad, Bengt, Seshadri, Sudha, Sever, Peter, Shrestha, Smeeta, Smith, Blair H., Smith, Jennifer A., Soranzo, Nicole, Sotoodehnia, Nona, Southam, Lorraine, Stanton, Alice V., Stathopoulou, Maria G., Strauch, Konstantin, Strawbridge, Rona J., Suderman, Matthew J., Tandon, Nikhil, Tang, Sian Tsun, Taylor, Kent D., Tayo, Bamidele O., Töglhofer, Anna Maria, Tomaszewski, Maciej, Tšernikova, Natalia, Tuomilehto, Jaakko, Uitterlinden, Andre G., Vaidya, Dhananjay, Van Hylckama Vlieg, Astrid, Van Setten, Jessica, Vasankari, Tuula, Vedantam, Sailaja, Vlachopoulou, Efthymia, Vozzi, Diego, Vuoksimaa, Eero, Waldenberger, Melanie, Ware, Erin B., Wentworth Shields, William, Whitfield, John B., Wild, Sarah, Willemsen, Gonneke, Yajnik, Chittaranjan S., Yao, Jie, Zaza, Gianluigi, Zhu, Xiaofeng, Salem, Rany M., Melbye, Mad, Bisgaard, Han, Samani, Nilesh J., Cusi, Daniele, Mackey, David A., Cooper, Richard S., Froguel, Philippe, Pasterkamp, Gerard, Grant, Struan F. A., Hakonarson, Hakon, Ferrucci, Luigi, Scott, Robert A., Morris, Andrew D., Palmer, Colin N. A., Dedoussis, George, Deloukas, Pano, Bertram, Lar, Lindenberger, Ulman, Berndt, Sonja I., Lindgren, Cecilia M., Timpson, Nicholas J., Tönjes, Anke, Munroe, Patricia B., Sørensen, Thorkild I. A., Rotimi, Charles N., Arnett, Donna K., Oldehinkel, Albertine J., Kardia, Sharon L. R., Balkau, Beverley, Gambaro, Giovanni, Morris, Andrew P., Eriksson, Johan G., Wright, Margie J., Martin, Nicholas G., Hunt, Steven C., Starr, John M., Deary, Ian J., Griffiths, Lyn R., Tiemeier, Henning, Pirastu, Nicola, Kaprio, Jaakko, Wareham, Nicholas J., Pérusse, Loui, Wilson, James G., Girotto, Giorgia, Caulfield, Mark J., Raitakari, Olli, Boomsma, Dorret I., Gieger, Christian, Van Der Harst, Pim, Hicks, Andrew A., Kraft, Peter, Sinisalo, Juha, Knekt, Paul, Johannesson, Magnu, Magnusson, Patrik K. E., Hamsten, Ander, Schmidt, Reinhold, Borecki, Ingrid B., Vartiainen, Erkki, Becker, Diane M., Bharadwaj, Dwaipayan, Mohlke, Karen L., Boehnke, Michael, Van Duijn, Cornelia M., Sanghera, Dharambir K., Teumer, Alexander, Zeggini, Eleftheria, Metspalu, Andre, Gasparini, Paolo, Ulivi, Sheila, Ober, Carole, Toniolo, Daniela, Rudan, Igor, Porteous, David J., Ciullo, Marina, Spector, Tim D., Hayward, Caroline, Dupuis, Josée, Loos, Ruth J. F., Wright, Alan F., Chandak, Giriraj R., Vollenweider, Peter, Shuldiner, Alan R., Ridker, Paul M., Rotter, Jerome I., Sattar, Naveed, Gyllensten, Ulf, North, Kari E., Pirastu, Mario, Psaty, Bruce M., Weir, David R., Laakso, Markku, Gudnason, Vilmundur, Takahashi, Atsushi, Chambers, John C., Kooner, Jaspal S., Strachan, David P., Campbell, Harry, Hirschhorn, Joel N., Perola, Marku, Polašek, Ozren, Wilson, James F., Imperial College Healthcare NHS Trust- BRC Funding, National Institute for Health Research, BioBank Japan, Project, The BioBank Japan Project, Ehret, Georg Benedikt, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Cardiovascular Centre (CVC)

Subjects
Male, Netherlands Twin Register (NTR), Blood Pressure, BLOOD-PRESSURE, INTELLIGENCE, Runs of Homozygosity, DISEASE, Homozygosity, Cohort Studies, Cognition, Forced Expiratory Volume, GENETIC-VARIANTS, Inbreeding depression, Settore MED/14 - NEFROLOGIA, Inbreeding, Inbreeding, Evolutionary genetics, Quantitative trait loci, Non-U.S. Gov't, Dominance (genetics), ddc:616, Genetics, ARCHITECTURE, Genome, Multidisciplinary, Body Height/genetics, Research Support, Non-U.S. Gov't, Homozygote, Confounding, heterozygosity, inbreeding, genomics, QUANTITATIVE TRAITS, BioBank Japan Project, Biological Evolution, Multidisciplinary Sciences, Cholesterol, Phenotype, Cholesterol, LDL/genetics, Trait, Science & Technology - Other Topics, Educational Status, Female, Lung Volume Measurements, Human, INBREEDING DEPRESSION, Quantitative trait loci, Blood Pressure/genetics, General Science & Technology, Forced Expiratory Volume/genetics, Lung Volume Measurement, Quantitative trait locus, Biology, Research Support, Evolutionary genetics, Article, LDL, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Journal Article, Humans, Genetic association, Science & Technology, Genome, Human, ta1184, PATHWAYS, Cholesterol, LDL, Body Height, Educational Statu, ASSOCIATION ANALYSIS, Evolutionary biology, Genome, Human/genetics, ta1181, Cohort Studie, Meta-Analysis
Abstract

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Published
2015

44. The SNAP spectrograph

Author

Ealet, A., Bebek, C., Akerlof, C.W., Aldering, G., Amanullah, R., Astier, P., Barrelet, E., Bergstrom, L., Bercovitz, J., Bernstein, G.M., Bester, M., Bonissent, A., Bower, C.R., Carithers, W.C., Commins, E.D., Day, C., Deustua, S.E., DiGennaro, R.S., Ellis, R.S., Eriksson, M., Fruchter, A., Genat, J.-F., Goldhaber, G., Goobar, A., Groom, D.E., Harris, S.E., Harvey, P.R., Heetderks, H.D., Holland, S.E., Huterer, D., Karcher, A., Kim, A.G., Kolbe, W.F., Kireger, B., Lafever, R., Lamoureux, J., Lampton, M., Levi, M.E., Levin, D.S., Linder, E.V., Loken, S.C., Malina, R., Massey, R., McKay, T., McKee, S.M., Miquel, R., Moertsell, E., Mostek, N., Mufson, S., Musser, J.A., Nugent, P.E., Oluseyi, H.M., Pain, R., Palaio, N.P., Pankow, D.H., Perlmutter, S., Pratt, R., Prieto, E., Refregier, A., Rhodes, J., Robinson, K.E., Roe, N., Sholl, M., Schnubnell, M.S., Smadja, G., Smoot, G.F., Spadafora, A., Tarle, G., Tomasch, A.D., Von Der Lippe, H., Vincent, D., Walder, J.-P., Wang, Gang, Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), and Flores, Sylvie

Subjects
[PHYS.ASTR.CO]Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], [PHYS.ASTR.CO] Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], Astrophysics::High Energy Astrophysical Phenomena, Astrophysics::Solar and Stellar Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, [SDU.ASTR] Sciences of the Universe [physics]/Astrophysics [astro-ph], Astrophysics::Galaxy Astrophysics
Abstract

Supernovae

Published
2002

45. Bmp2 gene in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

Author

Yang, W., primary, Guo, D., additional, Harris, M.A., additional, Cui, Y., additional, Gluhak-Heinrich, J., additional, Wu, J., additional, Chen, X.-D., additional, Skinner, C, additional, Nyman, J., additional, Edwards, J.R., additional, Mundy, G.R., additional, Lichtler, A., additional, Kream, B., additional, Rowe, D., additional, Kalajzic, I., additional, David, V., additional, Quarles, D., additional, Villareal, D., additional, Scott, Greg, additional, Ray, Manas, additional, Liu, S., additional, Martin, J.F., additional, Mishina, Y., additional, and Harris, S.E., additional

Published
2013
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46. X-ray / Optical Sum Frequency Generation

Author

Glover, T.E., primary, Fritz, D.M., additional, Cammarata, M., additional, Allison, T.K., additional, Coh, Sinisa, additional, Feldkamp, J.M., additional, Lemke, H., additional, Zhu, D., additional, Feng, Y., additional, Coffee, R.N., additional, Fuchs, M., additional, Ghimire, S., additional, Chen, J., additional, Shwartz, S., additional, Reis, D.A., additional, Harris, S.E., additional, and Hastings, J. B., additional

Published
2013
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48. X-ray / Optical Wave Mixing

Author

Glover, T.E., primary, Allison, T.K., additional, Cammarata, M., additional, Feldkamp, J., additional, Fritz, D.M., additional, Hastings, J.B., additional, Harris, S.E., additional, Reis, D.A., additional, and Schwarz, S., additional

Published
2011
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