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101. Ascorbic acid metabolites are involved in intraocular pressure control in the general population

Author

Hysi, Pirro G, Khawaja, Anthony P, Menni, Cristina, Tamraz, Bani, Wareham, Nick, Khaw, Kay-Tee, Foster, Paul J, Benet, Leslie Z, Spector, Tim D, and Hammond, Chris J

Subjects
Adult, Male, Multi-omics, genetic structures, Intraocular pressure, Ascorbate metabolism, Glaucoma, Ascorbic Acid, Middle Aged, eye diseases, 3. Good health, Metabolome, Humans, Metabolomics, Female, Public Health Surveillance, sense organs, Aged
Abstract

Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Mechanisms involved in its homeostasis are not well understood, but associations between metabolic factors and IOP have been reported. To investigate the relationship between levels of circulating metabolites and IOP, we performed a metabolome-wide association using a machine learning algorithm, and then employing Mendelian Randomization models to further explore the strength and directionality of effect of the metabolites on IOP. We show that O-methylascorbate, a circulating Vitamin C metabolite, has a significant IOP-lowering effect, consistent with previous knowledge of the anti-hypertensive and anti-oxidative role of ascorbate compounds. These results enhance understanding of IOP control and may potentially benefit future IOP treatment and reduce vision loss from glaucoma.

102. Contemporary Art Society’s Annual Conference: On Collecting Performance Art

Author

Hammond, Chris, Obrist, Hans Ulrich, Wood, Catherine, Chetwynd, Marvin Gaye, and Lydiate, Henry

Abstract

INTRODUCTION\ud \ud Now in its sixth year, the Contemporary Art Society’s Annual Conference brings together a range of high profile speakers including artists, curators, gallerists and legal professionals, to address the subject of collecting performance art. The conference will focus on questions in relation to display and conservation, as well as ethical and legal matters, and all of this against the backdrop of the scarcity of performance art in public collections in this country.\ud \ud Traditionally performance art has not enjoyed the same commercial success as other mediums, such as painting, sculpture or works on paper. As a result fewer works of this medium exist in public and private collections. However, this is now gradually beginning to change as we start to see significant performance artworks from the 1960s and 1970s, as well as works by contemporary artists, being acquired more frequently.\ud \ud What once prohibited many performance works from entering the market was the works lack of autonomy or ability to exist independently from the artist. In many cases this has now been reframed in such a way that works entering collections have often been created to no longer be dependent on the artist as performer. However, what is particular to this medium is the artists’ ongoing relationship with their works, which as a result, demands new and pioneering methods of research and collaboration to ensure public collections can continue to acquire works in perpetuity. How can we develop a culture of confident problem solving in relation to the conservation of unfamiliar and sometimes unstable media? How can we ensure conservation knowledge is evenly spread and accessible across the sector? How do curatorial, exhibition and conservation team’s work together to find the solutions that will enable us to acquire works by artists of our time and to ensure that they can be experienced in the future?\ud \ud Keynote Speaker: Hans Ulrich Obrist, Co-Director, Exhibitions and Programmes and Director of International Projects, Serpentine Galleries, Catherine Wood, Curator of Contemporary Art and Performance, Tate Modern,Marvin Gaye Chetwynd, Artist, Henry Lydiate, Creative Arts Business Consultancy and Chris Hammond, Director, MOT International.\ud \ud SCHEDULE\ud \ud 14.10 – 14.40\ud Chris Hammond, Director, MOT International\ud Chris Hammond will discuss approaches to collecting contemporary performance, in addition to the current markets for performance documentation, particularly in relation to practices from the 1970′s. Hammond will discuss key examples that emphasise his gallery’s particular strength in performance-based practice, including artists Cally Spooner, Katrina Palmer, Dennis Oppenheim, Ulay, and Laure Provost.\ud \ud SPEAKERS BIOGRAPHIES’\ud \ud Chris Hammond\ud Chris Hammond founded commercial gallery MOT International in 2006, opening a second space in Brussels in 2011. In 2015 the gallery will open a third space, also in Brussels, on the Avenue Louise, expanding the scale and ambition of the exhibition programme. At MOT International, Hammond established the early careers of artists such as 2012 Turner Prize winner Elizabeth Price, and 2013 Turner Prize winner Laure Prouvost. The gallery has concentrated on developing a programme that foregrounds a high proportion of conceptual, video and performance based practice, particularly with historically-significant artists who have been under-represented in European and US markets. In the last three years, Hammond has expanded the roster to work with artists such as Ulay, Dennis Oppenheim, Braco Dimitrijevic, Seung-Taek Lee and Nil Yalter. As an independent curator, Hammond has worked with artists such as Mike Kelley, Martin Kippenberger, Paul McCarthy, Derek Jarman, Stephen Willats and Omer Fast.

103. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Author

Gharahkhani, Puya, Jorgenson, Eric, Hysi, Pirro, Khawaja, Anthony P, Pendergrass, Sarah, Han, Xikun, Ong, Jue Sheng, Hewitt, Alex W, Segrè, Ayellet V, Rouhana, John M, Hamel, Andrew R, Igo, Robert P, Choquet, Helene, Qassim, Ayub, Josyula, Navya S, Cooke Bailey, Jessica N, Bonnemaijer, Pieter WM, Iglesias, Adriana, Siggs, Owen M, Young, Terri L, Vitart, Veronique, Thiadens, Alberta AHJ, Karjalainen, Juha, Uebe, Steffen, Melles, Ronald B, Nair, K Saidas, Luben, Robert, Simcoe, Mark, Amersinghe, Nishani, Cree, Angela J, Hohn, Rene, Poplawski, Alicia, Chen, Li Jia, Rong, Shi-Song, Aung, Tin, Vithana, Eranga Nishanthie, NEIGHBORHOOD Consortium, ANZRAG Consortium, Biobank Japan Project, FinnGen Study, UK Biobank Eye And Vision Consortium, GIGA Study Group, 23 And Me Research Team, Tamiya, Gen, Shiga, Yukihiro, Yamamoto, Masayuki, Nakazawa, Toru, Currant, Hannah, Birney, Ewan, Wang, Xin, Auton, Adam, Lupton, Michelle K, Martin, Nicholas G, Ashaye, Adeyinka, Olawoye, Olusola, Williams, Susan E, Akafo, Stephen, Ramsay, Michele, Hashimoto, Kazuki, Kamatani, Yoichiro, Akiyama, Masato, Momozawa, Yukihide, Foster, Paul J, Khaw, Peng T, Morgan, James E, Strouthidis, Nicholas G, Kraft, Peter, Kang, Jae H, Pang, Chi Pui, Pasutto, Francesca, Mitchell, Paul, Lotery, Andrew J, Palotie, Aarno, Van Duijn, Cornelia, Haines, Jonathan L, Hammond, Chris, Pasquale, Louis R, Klaver, Caroline CW, Hauser, Michael, Khor, Chiea Chuen, Mackey, David A, Kubo, Michiaki, Cheng, Ching-Yu, Craig, Jamie E, MacGregor, Stuart, and Wiggs, Janey L

Subjects
genetic structures, Asian People, Genotype, Genetic Loci, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, eye diseases, Glaucoma, Open-Angle, White People, 3. Good health, Genome-Wide Association Study
Abstract

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

104. The Commercial Dimensions of a Fine Art Practice

Author

Hammond, Chris, Lydiate, Henry, and Gluzberg, Margarita

Abstract

Art law expert and Art Monthly contributor Henry Lydiate and Chris Hammond, Director of MOT International, discuss the commercial dimensions of a fine art practice: appropriation, copyright, cultural commons, commissions, gallery deals and more. The conversation will be chaired by the artist and RCAFine Art Research Tutor Margarita Gluzberg.\ud \ud This event is highly recommended toall students, staff and recent graduates with a fine art practice or interest. It has been organised with the support of the RCA School of Fine Art. Watch Henry's Artlaw interviews with leading artists on these topics.

105. Sixteen new lung function signals identified through 1000 genomes project reference panel imputation

Author

Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., BiLeve, U. K., Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., and Tobin, Martin D.

Subjects
3. Good health

106. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author

Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., Tobin, Martin D., Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., and Tobin, Martin D.

Abstract

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

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107. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author

Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., Tobin, Martin D., Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., and Tobin, Martin D.

Abstract

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

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108. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author

Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., Tobin, Martin D., Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., and Tobin, Martin D.

Abstract

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

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109. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author

Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., Tobin, Martin D., Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., and Tobin, Martin D.

Abstract

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

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110. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author

Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., Tobin, Martin D., Artigas, María Soler, Wain, Louise V., Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E., Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma’en, Trochet, Holly, McArdle, Wendy L., Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K., Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M., Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G., Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R., Grallert, Harald, Hammond, Chris J., Harris, Sarah E., Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P., Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W., Navarro, Pau, Nickle, David C., Padmanabhan, Sandosh, Raitakari, Olli T., Ried, Janina S., Ripatti, Samuli, Schulz, Holger, Scott, Robert A., Sin, Don D., Starr, John M., Deloukas, Panos, Hansell, Anna L., Hubbard, Richard, Jackson, Victoria E., Marchini, Jonathan, Pavord, Ian, Thomson, Neil C., Zeggini, Eleftheria, Viñuela, Ana, Völzke, Henry, Wild, Sarah H., Wright, Alan F., Zemunik, Tatijana, Jarvis, Deborah L., Spector, Tim D., Evans, David M., Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Karrasch, Stefan, Probst-Hensch, Nicole M., Heinrich, Joachim, Stubbe, Beate, Wilson, James F., Wareham, Nicholas J., James, Alan L., Morris, Andrew P., Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P., Hall, Ian P., and Tobin, Martin D.

Abstract

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

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111. Be a leading light for change.

Author

HAMMOND, CHRIS

Subjects
*IN-service training of teachers, *TEACHER development, *SENIOR leadership teams, *EMERGENCY management, *COMMUNICATION & society, SERVICES for teachers
Abstract

The article offers suggestions on how to become a visible leader and earn respect from a large audience. It includes effective management of change to communicate with others, support the other senior leadership team and maintain calmness in dealing with an emergency situation or and injured child. Also emphasized is the roaming into classrooms for lesson observation.

Published
2015

112. Letters.

Author

Hunt, J., Clarke, Philip, Pattison, Stuart, Crisp, Geoffrey, Wilson, Alec, Maddocks, Gordon, Eaton, Charles, Hammond, Chris, Birkby, Jane, de Winne, Terry, Markham, Gary, Nash, Tess, Palmer, D. H., and Lake, C. A.

Subjects
LETTERS to the editor, LICENSES, FARMERS, TRACTORS, TAXATION
Abstract

Presents letters to the editor in response to articles and topics discussed in previous issues. Declaration of farm licensing in Scotland; Applications for the Voluntary Initiative; Suggestions to farmers who are driving tractors on the road; Discussion of tax matters relating to agriculture.

Published
2004

113. Rule #1: The Customer Is Always Right Customer Service Meets Communications.

Author

Hammond, Chris

Abstract

The article discusses customer service and communication working hand in hand. A few best practices cited by Chris Hammond, communications director of Wells Fargo, include using the structure to one's own advantage, starting good customer service internally and taking customer service seriously. For Linda Rutherford, vice president of public relations for Southwest Airlines, communications should always be aligned, communicate with customers before they get the chance to complain and start with one core communication.

Published
2007

114. WHRADA.

Author

Hammond, Chris

Abstract

The article mentioned the coin and artefact which are found in the month of May including Cow horn protector, a club site artefact, Hanry II cut half, a club site coin and James I sixpence love token, an own site artefact.

Published
2015

115. A Brief Primer on Quantitative Measurement for the OD Professional.

Author

Wagner, Sharon, Goodin, Nichelle, and Hammond, Chris

Subjects
*ORGANIZATIONAL change, *INFERENTIAL statistics, *RELEVANCE, *QUANTITATIVE research, *ORGANIZATIONAL performance
Abstract

The article provides an account of basic statistics and measurement issues as applied to organization development (OD) including reliability and a sampling of inferential statistics. Topics include keeping in mind the characteristics such as relevance or acceptability, need of quantitative measurement in organizational intervention, and internal consistency estimate.

Published
2017

116. Genes are important in age-related nuclear cataracts.

Author

Charters, Lynda and Hammond, Chris

Subjects
*CATARACT in old age, *GENES, *HEALTH, *CATARACT, *DISEASE risk factors
Abstract

Presents information on a study led by ophthalmologist, Doctor Chris Hammond, that found the possibility that genetic influences may be involved in the development of age-related nuclear cataracts. How the density of the nuclear cataract was determined; Correlation of the objective and subjective measurements of cataract; Reason for the difficulties in identifying environmental risk factors for cataracts.

Published
2000

117. Intemporal Production Frontiers(Book).

Author

Hammond, Chris

Subjects
INTEMPORAL Production Frontiers With Dynamic DEA (Book)
Abstract

Reviews the book `Intemporal Production Frontiers With Dynamic DEA,' by Rolf Fare and Shawna Grosskopf.

Published
1998

118. Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma

Author

Janey L. Wiggs, UK Biobank Eye, Jessica N. Cooke Bailey, Jonathan L. Haines, Ching-Yu Cheng, Pirro G. Hysi, Mark James Simcoe, Anthony P Khawaja, Paul J. Foster, Christopher J Hammond, Peng T. Khaw, Louis R. Pasquale, Yeunjoo E. Song, Robert A. Scott, Robert Wojciechowski, Nicholas J. Wareham, Robert P. Igo, Khawaja, Anthony P [0000-0001-6802-8585], Cooke Bailey, Jessica N [0000-0002-4001-8702], Simcoe, Mark [0000-0003-2432-0810], Pasquale, Louis R [0000-0002-5835-3496], Haines, Jonathan L [0000-0002-4351-4728], Foster, Paul J [0000-0002-4755-177X], Wiggs, Janey L [0000-0003-1890-3278], Hammond, Chris J [0000-0002-3227-2620], Hysi, Pirro G [0000-0001-5752-2510], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Adult, Male, Intraocular pressure, Open angle glaucoma, genetic structures, Glaucoma, Genome-wide association study, Disease, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Genetics, medicine, Humans, Genetic Predisposition to Disease, Risk factor, Intraocular Pressure, Aged, Middle Aged, medicine.disease, eye diseases, 3. Good health, 030104 developmental biology, Genetic Loci, Cohort, 030221 ophthalmology & optometry, Female, sense organs, Glaucoma, Open-Angle, Cohort study, Genome-Wide Association Study
Abstract

Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.

Published
2018

119. Letters.

Author

Glasgow, Raghnall, Dreese, Mia, Fawcett, Ian, Crinson, Clare, Ben-Tovim, Atarah, and Hammond, Chris

Subjects
*FLUTE makers, *GENDER, *MUSIC education
Abstract

Several letters to the editor are presented in response to articles in previous issues including flute makers in the December 2013 issue, the new features of the publication, and gender issues in music education.

Published
2012

120. A genome-wide analysis of 340 318 participants identifies four novel loci associated with the age of first spectacle wear.

Author

Patasova K, Khawaja AP, Wojciechowski R, Mahroo OA, Falchi M, Rahi JS, Hammond CJ, and Hysi PG

Subjects
Adult, Eyeglasses, Genome-Wide Association Study, Humans, Myopia genetics, Refractive Errors genetics
Abstract

Refractive errors, particularly myopia, are the most common eye conditions, often leading to serious visual impairment. The age of onset is correlated with the severity of refractive error in adulthood observed in epidemiological and genetic studies and can be used as a proxy in refractive error genetic studies. To further elucidate genetic factors that influence refractive error, we analysed self-reported age of refractive error correction data from the UK Biobank European and perform genome-wide time-to-event analyses on the age of first spectacle wear (AFSW). Genome-wide proportional hazards ratio analyses were conducted in 340 318 European subjects. We subsequently assessed the similarities and differences in the genetic architectures of refractive error correction from different causes. All-cause AFSW was genetically strongly correlated (rg = -0.68) with spherical equivalent (the measured strength of spectacle lens required to correct the refractive error) and was used as a proxy for refractive error. Time-to-event analyses found genome-wide significant associations at 44 independent genomic loci, many of which (GJD2, LAMA2, etc.) were previously associated with refractive error. We also identified six novel regions associated with AFSW, the most significant of which was on chromosome 17q (P = 3.06 × 10-09 for rs55882072), replicating in an independent dataset. We found that genes associated with AFSW were significantly enriched for expression in central nervous system tissues and were involved in neurogenesis. This work demonstrates the merits of time-to-event study design in the genetic investigation of refractive error and contributes additional knowledge on its genetic risk factors in the general population., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Published
2022
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121. Correction: Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.

Author

Currant H, Hysi P, Fitzgerald TW, Gharahkhani P, Bonnemaijer PWM, Senabouth A, Hewitt AW, Atan D, Aung T, Charng J, Choquet H, Craig J, Khaw PT, Klaver CCW, Kubo M, Ong JS, Pasquale LR, Reisman CA, Daniszewski M, Powell JE, Pébay A, Simcoe MJ, Thiadens AAHJ, van Duijn CM, Yazar S, Jorgenson E, MacGregor S, Hammond CJ, Mackey DA, Wiggs JL, Foster PJ, Patel PJ, Birney E, and Khawaja AP

Abstract

[This corrects the article DOI: 10.1371/journal.pgen.1009497.].

Published
2021
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122. Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.

Author

Currant H, Hysi P, Fitzgerald TW, Gharahkhani P, Bonnemaijer PWM, Senabouth A, Hewitt AW, Atan D, Aung T, Charng J, Choquet H, Craig J, Khaw PT, Klaver CCW, Kubo M, Ong JS, Pasquale LR, Reisman CA, Daniszewski M, Powell JE, Pébay A, Simcoe MJ, Thiadens AAHJ, van Duijn CM, Yazar S, Jorgenson E, MacGregor S, Hammond CJ, Mackey DA, Wiggs JL, Foster PJ, Patel PJ, Birney E, and Khawaja AP

Subjects
Female, Genotype, Glaucoma genetics, Glaucoma pathology, Hair Color genetics, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide genetics, Quality Control, Retina pathology, United Kingdom, Vision Disorders, Visual Acuity genetics, Biological Specimen Banks, Genetic Variation, Phenotype, Retina metabolism, Tomography, Optical Coherence
Abstract

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: APK is a paid consultant to Aerie, Allergan, Google Health, Novartis, Reichert, Santen and Thea. LRP is consultant for Verily, Eyenovia, Bausch+Lomb, and Nicox. JW is consultant for Allergan, Editas, Maze, Regenxbio and has a sponsored research grant from Aerpio.

Published
2021
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123. Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort: The UK Biobank.

Author

Khawaja AP, Chua S, Hysi PG, Georgoulas S, Currant H, Fitzgerald TW, Birney E, Ko F, Yang Q, Reisman C, Garway-Heath DF, Hammond CJ, Khaw PT, Foster PJ, Patel PJ, and Strouthidis N

Subjects
Adult, Age Factors, Aged, Area Under Curve, Biological Specimen Banks, Body Constitution, Body Mass Index, Cohort Studies, Cross-Sectional Studies, Ethnicity, Female, Humans, Intraocular Pressure physiology, Male, Middle Aged, ROC Curve, Sex Factors, Tomography, Optical Coherence, United Kingdom, Nerve Fibers physiology, Retinal Ganglion Cells physiology
Abstract

Purpose: To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell-inner plexiform layer (GCIPL) thicknesses in a large cohort., Design: Cross-sectional study., Participants: We included 42 044 participants in the UK Biobank. The mean age was 56 years., Methods: Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc., Main Outcome Measures: Thicknesses of mRNFL, GCC, and GCIPL., Results: We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: -0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61-0.30]; P = 1.1×10 -8 ), greater social deprivation (most significant for GCIPL: -0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, -0.42 to -0.14]; P = 6.6×10 -5 ), lower educational attainment (most significant for mRNFL: -0.36 μm for less than O level compared with degree level [95% CI, -0.45 to 0.26]; P = 2.3×10 -14 ), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: -1.65 μm [95% CI, -1.86 to -1.43]; P = 2.4×10 -50 ). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (-0.04 μm/mmHg [95% CI, -0.05 to -0.03]; P = 4.0×10 -10 ) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, -0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%)., Conclusions: The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Published
2020
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124. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.

Author

Soler Artigas M, Wain LV, Miller S, Kheirallah AK, Huffman JE, Ntalla I, Shrine N, Obeidat M, Trochet H, McArdle WL, Alves AC, Hui J, Zhao JH, Joshi PK, Teumer A, Albrecht E, Imboden M, Rawal R, Lopez LM, Marten J, Enroth S, Surakka I, Polasek O, Lyytikäinen LP, Granell R, Hysi PG, Flexeder C, Mahajan A, Beilby J, Bossé Y, Brandsma CA, Campbell H, Gieger C, Gläser S, González JR, Grallert H, Hammond CJ, Harris SE, Hartikainen AL, Heliövaara M, Henderson J, Hocking L, Horikoshi M, Hutri-Kähönen N, Ingelsson E, Johansson Å, Kemp JP, Kolcic I, Kumar A, Lind L, Melén E, Musk AW, Navarro P, Nickle DC, Padmanabhan S, Raitakari OT, Ried JS, Ripatti S, Schulz H, Scott RA, Sin DD, Starr JM, Viñuela A, Völzke H, Wild SH, Wright AF, Zemunik T, Jarvis DL, Spector TD, Evans DM, Lehtimäki T, Vitart V, Kähönen M, Gyllensten U, Rudan I, Deary IJ, Karrasch S, Probst-Hensch NM, Heinrich J, Stubbe B, Wilson JF, Wareham NJ, James AL, Morris AP, Jarvelin MR, Hayward C, Sayers I, Strachan DP, Hall IP, and Tobin MD

Subjects
Adult, Aged, Aged, 80 and over, Female, Forced Expiratory Volume, Humans, Lung Diseases physiopathology, Male, Middle Aged, Polymorphism, Single Nucleotide, White People genetics, Young Adult, Genome-Wide Association Study, Lung physiopathology, Lung Diseases genetics
Abstract

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

Published
2015
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125. Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.

Author

Simpson CL, Wojciechowski R, Oexle K, Murgia F, Portas L, Li X, Verhoeven VJ, Vitart V, Schache M, Hosseini SM, Hysi PG, Raffel LJ, Cotch MF, Chew E, Klein BE, Klein R, Wong TY, van Duijn CM, Mitchell P, Saw SM, Fossarello M, Wang JJ, Polašek O, Campbell H, Rudan I, Oostra BA, Uitterlinden AG, Hofman A, Rivadeneira F, Amin N, Karssen LC, Vingerling JR, Döring A, Bettecken T, Bencic G, Gieger C, Wichmann HE, Wilson JF, Venturini C, Fleck B, Cumberland PM, Rahi JS, Hammond CJ, Hayward C, Wright AF, Paterson AD, Baird PN, Klaver CC, Rotter JI, Pirastu M, Meitinger T, Bailey-Wilson JE, and Stambolian D

Subjects
Adult, Age of Onset, Aged, Aged, 80 and over, Alleles, Female, Genetic Association Studies, Genetic Markers genetics, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, White People genetics, Eye physiopathology, Hyperopia genetics, Myopia genetics
Abstract

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Published
2014
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126. The Roles of PAX6 and SOX2 in Myopia: lessons from the 1958 British Birth Cohort.

Author

Simpson CL, Hysi P, Bhattacharya SS, Hammond CJ, Webster A, Peckham CS, Sham PC, and Rahi JS

Subjects
Adult, Cohort Studies, Female, Genotype, Humans, Male, Middle Aged, PAX6 Transcription Factor, Polymorphism, Single Nucleotide, Quantitative Trait Loci, SOXB1 Transcription Factors, United Kingdom, Eye Proteins physiology, HMGB Proteins physiology, Homeodomain Proteins physiology, Myopia genetics, Paired Box Transcription Factors physiology, Repressor Proteins physiology, Transcription Factors physiology
Abstract

Purpose: Myopia is a common complex trait that affects up to 60% of some populations. Its development is influenced by multiple genes and environmental factors. PAX6 and SOX2 are genes with fundamental roles in ocular growth and development, and they have been linked with myopia in a recent linkage study. The authors investigated the roles of PAX6 and SOX2 in common myopia as part of a broader association study of refractive error., Methods: Five hundred ninety-six persons from the 1958 British Birth Cohort, a nationally representative population, were randomly selected from the outer tertiles of the refractive error (RE) distribution and were genotyped using 25 tagSNPs across PAX6 and 3 tagSNPs across SOX2 and their putative control regions. This experiment had 80% power to exclude either gene contributing more than 10% of the variance of refractive error., Results: All SNPs were in Hardy-Weinberg equilibrium, and the genotyping failure rate was less than 5%. Accounting for multiple testing, no significant association (P < 0.05) was found between any of the SNPs or haplotypes and refractive error., Conclusions: PAX6 and SOX2 are obvious candidates in RE genetic studies because of their biological roles and prior linkage studies. The present findings strongly suggest refractive error is not directly affected in this population by variants in either gene or by their known promoters/enhancers. The authors suggest that neither PAX6 nor SOX2 should be prioritized in the international search for genetic modifiers of refractive error. Their findings contribute to broader understanding of the pathophysiology of refractive error and highlight the critical role of replication in genetic research on complex disorders.

Published
2007
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