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6 results on '"UK Biobank"'

1. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population.

Author

Stuart, KV, Biradar, MI, Luben, RN, Dhaun, N, Wagner, SK, Warwick, AN, Sun, Z, Madjedi, KM, Pasquale, LR, Wiggs, JL, Kang, JH, Lentjes, MAH, Aschard, H, Kim, J, Foster, PJ, Khawaja, AP, Modifiable Risk Factors for Glaucoma Collaboration, UK Biobank Eye and Vision Consortium, International Glaucoma Genetics Consortium, Stuart, KV, Biradar, MI, Luben, RN, Dhaun, N, Wagner, SK, Warwick, AN, Sun, Z, Madjedi, KM, Pasquale, LR, Wiggs, JL, Kang, JH, Lentjes, MAH, Aschard, H, Kim, J, Foster, PJ, Khawaja, AP, Modifiable Risk Factors for Glaucoma Collaboration, UK Biobank Eye and Vision Consortium, and International Glaucoma Genetics Consortium

Abstract

PURPOSE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P < 0.001) and prevalence of

Published
2024

2. The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts.

Author

Madjedi, KM, Stuart, KV, Chua, SYL, Luben, RN, Warwick, A, Pasquale, LR, Kang, JH, Wiggs, JL, Lentjes, MAH, Aschard, H, Sattar, N, Foster, PJ, Khawaja, AP, Modifiable Risk Factors for Glaucoma Collaboration and the UK Biobank Eye and Vision Consortium, Madjedi, KM, Stuart, KV, Chua, SYL, Luben, RN, Warwick, A, Pasquale, LR, Kang, JH, Wiggs, JL, Lentjes, MAH, Aschard, H, Sattar, N, Foster, PJ, Khawaja, AP, and Modifiable Risk Factors for Glaucoma Collaboration and the UK Biobank Eye and Vision Consortium

Abstract

PURPOSE: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). DESIGN: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. PARTICIPANTS: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. METHODS: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). MAIN OUTCOME MEASURES: Corneal-compensated IOP. RESULTS: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06-0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08-0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05-0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07-0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03-0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06-0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (-0.05 mmHg; 95% CI, -0.08 to -0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). CONCLUSIONS: Our findings suggest that serum TC, HDL-C, and LDL-C are a

Published
2022

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

Author

Gharahkhani, Puya, 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, Wiggs, Janey L, Gharahkhani, Puya, 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

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.

Published
2021

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

Author

Gharahkhani, Puya, 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, Wiggs, Janey L, Gharahkhani, Puya, 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

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.

Published
2021

5. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters.

Author

Bonnemaijer, Pieter WM, Bonnemaijer, Pieter WM, Leeuwen, Elisabeth M van, Iglesias, Adriana I, Gharahkhani, Puya, Vitart, Veronique, Khawaja, Anthony P, Simcoe, Mark, Höhn, René, Cree, Angela J, Igo, Rob P, International Glaucoma Genetics Consortium, NEIGHBORHOOD consortium, UK Biobank Eye and Vision Consortium, Gerhold-Ay, Aslihan, Nickels, Stefan, Wilson, James F, Hayward, Caroline, Boutin, Thibaud S, Polašek, Ozren, Aung, Tin, Khor, Chiea Chuen, Amin, Najaf, Lotery, Andrew J, Wiggs, Janey L, Cheng, Ching-Yu, Hysi, Pirro G, Hammond, Christopher J, Thiadens, Alberta AHJ, MacGregor, Stuart, Klaver, Caroline CW, Duijn, Cornelia M van, Bonnemaijer, Pieter WM, Bonnemaijer, Pieter WM, Leeuwen, Elisabeth M van, Iglesias, Adriana I, Gharahkhani, Puya, Vitart, Veronique, Khawaja, Anthony P, Simcoe, Mark, Höhn, René, Cree, Angela J, Igo, Rob P, International Glaucoma Genetics Consortium, NEIGHBORHOOD consortium, UK Biobank Eye and Vision Consortium, Gerhold-Ay, Aslihan, Nickels, Stefan, Wilson, James F, Hayward, Caroline, Boutin, Thibaud S, Polašek, Ozren, Aung, Tin, Khor, Chiea Chuen, Amin, Najaf, Lotery, Andrew J, Wiggs, Janey L, Cheng, Ching-Yu, Hysi, Pirro G, Hammond, Christopher J, Thiadens, Alberta AHJ, MacGregor, Stuart, Klaver, Caroline CW, and Duijn, Cornelia M van

Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Published
2019

6. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters.

Author

Bonnemaijer, Pieter WM, Bonnemaijer, Pieter WM, Leeuwen, Elisabeth M van, Iglesias, Adriana I, Gharahkhani, Puya, Vitart, Veronique, Khawaja, Anthony P, Simcoe, Mark, Höhn, René, Cree, Angela J, Igo, Rob P, International Glaucoma Genetics Consortium, NEIGHBORHOOD consortium, UK Biobank Eye and Vision Consortium, Gerhold-Ay, Aslihan, Nickels, Stefan, Wilson, James F, Hayward, Caroline, Boutin, Thibaud S, Polašek, Ozren, Aung, Tin, Khor, Chiea Chuen, Amin, Najaf, Lotery, Andrew J, Wiggs, Janey L, Cheng, Ching-Yu, Hysi, Pirro G, Hammond, Christopher J, Thiadens, Alberta AHJ, MacGregor, Stuart, Klaver, Caroline CW, Duijn, Cornelia M van, Bonnemaijer, Pieter WM, Bonnemaijer, Pieter WM, Leeuwen, Elisabeth M van, Iglesias, Adriana I, Gharahkhani, Puya, Vitart, Veronique, Khawaja, Anthony P, Simcoe, Mark, Höhn, René, Cree, Angela J, Igo, Rob P, International Glaucoma Genetics Consortium, NEIGHBORHOOD consortium, UK Biobank Eye and Vision Consortium, Gerhold-Ay, Aslihan, Nickels, Stefan, Wilson, James F, Hayward, Caroline, Boutin, Thibaud S, Polašek, Ozren, Aung, Tin, Khor, Chiea Chuen, Amin, Najaf, Lotery, Andrew J, Wiggs, Janey L, Cheng, Ching-Yu, Hysi, Pirro G, Hammond, Christopher J, Thiadens, Alberta AHJ, MacGregor, Stuart, Klaver, Caroline CW, and Duijn, Cornelia M van

Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Published
2019

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