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1. Neural correlates of cognitive ability and visuo-motor speed: validation of IDoCT on UK Biobank Data

Author

Giunchiglia, Valentina, Curtis, Sharon, Smith, Stephen, Allen, Naomi, and Hampshire, Adam

Subjects
Quantitative Biology - Neurons and Cognition, Quantitative Biology - Quantitative Methods
Abstract

Automated online and App-based cognitive assessment tasks are becoming increasingly popular in large-scale cohorts and biobanks due to advantages in affordability, scalability and repeatability. However, the summary scores that such tasks generate typically conflate the cognitive processes that are the intended focus of assessment with basic visuomotor speeds, testing device latencies and speed-accuracy tradeoffs. This lack of precision presents a fundamental limitation when studying brain-behaviour associations. Previously, we developed a novel modelling approach that leverages continuous performance recordings from large-cohort studies to achieve an iterative decomposition of cognitive tasks (IDoCT), which outputs data-driven estimates of cognitive abilities, and device and visuomotor latencies, whilst recalibrating trial-difficulty scales. Here, we further validate the IDoCT approach with UK BioBank imaging data. First, we examine whether IDoCT can improve ability distributions and trial-difficulty scales from an adaptive picture-vocabulary task (PVT). Then, we confirm that the resultant visuomotor and cognitive estimates associate more robustly with age and education than the original PVT scores. Finally, we conduct a multimodal brain-wide association study with free-text analysis to test whether the brain regions that predict the IDoCT estimates have the expected differential relationships with visuomotor vs. language and memory labels within the broader imaging literature. Our results support the view that the rich performance timecourses recorded during computerised cognitive assessments can be leveraged with modelling frameworks like IDoCT to provide estimates of human cognitive abilities that have superior distributions, re-test reliabilities and brain-wide associations.

Published
2023

5. Periodontitis and Outer Retinal Thickness: a Cross-Sectional Analysis of the United Kingdom Biobank Cohort

Author

Allen, Naomi, Aslam, Tariq, Atan, Denize, Balaskas, Konsantinos, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Black, Graeme, Braithwaite, Tasanee, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Chua, Sharon Y.L., Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D., Doney, Alexander, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John E.J., Garway-Heath, David F., Gibson, Jane, Guggenheim, Jeremy A., Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Hysi, Pirro, Keane, Pearse A., Khaw, Sir Peng T., Khawaja, Anthony P., Lascaratos, Gerassimos, Littlejohns, Thoams, Lotery, Andrew J., Luben, Robert, Luthert, Phil, Macgillivray, Tom, Mackie, Sarah, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Moore, Tony, Morgan, James E., O’Sullivan, Eoin, Oram, Richard, Owen, Chris G., Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rahi, Jugnoo S., Rudnikca, Alicja R., Sattar, Naveed, Self, Jay, Sergouniotis, Panagiotis, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Sun, Zihan, Tapp, Robyn, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Viswanathan, Ananth C., Weedon, Mike, Williams, Cathy, Williams, Katie, Woodside, Jayne V., Yates, Max M., Yip, Jennifer, Zheng, Yalin, Wagner, Siegfried K., Patel, Praveen J., Huemer, Josef, Khalid, Hagar, Stuart, Kelsey V., Chu, Colin J., Williamson, Dominic J., Struyven, Robbert R., Romero-Bascones, David, Foster, Paul J., Balaskas, Konstantinos, Cortina-Borja, Mario, Chapple, Iain, Dietrich, Thomas, and Denniston, Alastair K.

Published
2024
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6. Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank

Author

Allen, Naomi, Aslam, Tariq, Atan, Denize, Balaskas, Konstantinos, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Black, Graeme, Braithwaite, Tasanee, Carare, Roxana, Chakravarthy, Usha, Chan, Michelle, Chua, Sharon, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew, Doney, Alexander, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John, Garway-heath, David (Ted), Gibson, Jane, Guggenheim, Jeremy, Hammond, Chris, Hardcastle, Alison, Harding, Simon, Hogg, Ruth, Hysi, Pirro, Keane, Pearse, Tee Khaw, Sir Peng, Khawaja, Anthony, Lascaratos, Gerassimos, Littlejohns, Thomas, Lotery, Andrew, Luben, Robert, Luthert, Phil, Macgillivray, Tom, Mackie, Sarah, Madhusudhan, Savita, Mcguinness, Bernadette, Mckay, Gareth, Mckibbin, Martin, Moore, Tony, Morgan, James, O'sullivan, Eoin, Oram, Richard, Owen, Chris, Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Pontikos, Nikolas, Rahi, Jugnoo, Rudnicka, Alicja, Sattar, Naveed, Self, Jay, Sergouniotis, Panagiotis, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Sun, Zihan, Tapp, Robyn, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Viswanathan, Ananth, Vitart, Veronique, Weedon, Mike, Williams, Katie, Williams, Cathy, Woodside, Jayne, Yates, Max, Zheng, Yalin, Thomas, Mervyn, Wagner, Siegfried Karl, Bountziouka, Vasiliki, and Rahi, Jugnoo Sangeeta

Published
2024
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9. A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Author

Bailey-Wilson, Joan E., Baird, Paul N., Barathi, Veluchamy A., Biino, Ginevra, Burdon, Kathryn P., Campbell, Harry, Chen, Li Jia, Cheng, Ching-Yu, Chew, Emily Y., Craig, Jamie E., Deangelis, Margaret M., Delcourt, Cécile, Ding, Xiaohu, Fan, Qiao, Fossarello, Maurizio, Foster, Paul J., Gharahkhani, Puya, Guggenheim, Jeremy A., Guo, Xiaobo, Haarman, Annechien E.G., Haller, Toomas, Hammond, Christopher J., Han, Xikun, Hayward, Caroline, He, Mingguang, Hewitt, Alex W., Hoang, Quan, Hysi, Pirro G., Iglesias, Adriana I., Igo, Robert P., Iyengar, Sudha K., Jonas, Jost B., Kähönen, Mika, Kaprio, Jaakko, Khawaja, Anthony P., Klein, Barbara E., Lass, Jonathan H., Lee, Kris, Lehtimäki, Terho, Lewis, Deyana, Li, Qing, Li, Shi-Ming, Lyytikäinen, Leo-Pekka, MacGregor, Stuart, Mackey, David A., Martin, Nicholas G., Meguro, Akira, Metspalu, Andres, Middlebrooks, Candace, Miyake, Masahiro, Mizuki, Nobuhisa, Musolf, Anthony, Nickels, Stefan, Oexle, Konrad, Pang, Chi Pui, Pärssinen, Olavi, Paterson, Andrew D., Pfeiffer, Norbert, Polasek, Ozren, Rahi, Jugnoo S., Raitakari, Olli, Rudan, Igor, Sahebjada, Srujana, Saw, Seang-Mei, Simpson, Claire L., Stambolian, Dwight, Tai, E-Shyong, Tedja, Milly S., Tideman, J. Willem L., Tsujikawa, Akitaka, van Duijn, Cornelia M., Verhoeven, Virginie J.M., Vitart, Veronique, Wang, Ningli, Wang, Ya Xing, Wedenoja, Juho, Wei, Wen Bin, Williams, Cathy, Williams, Katie M., Wilson, James F., Wojciechowski, Robert, Yam, Jason C.S., Yamashiro, Kenji, Yap, Maurice K.H., Yazar, Seyhan, Yip, Shea Ping, Young, Terri L., Zhou, Xiangtian, Allen, Naomi, Aslam, Tariq, Atan, Denize, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Black, Graeme, Bunce, Catey, Carare, Roxana, Chakravarthy, Usha, Chan, Michelle, Chua, Sharon, Cipriani, Valentina, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew, Doney, Alexander, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John, Garway-Heath, David, Gibson, Jane, Gore, Dan, Guggenheim, Jeremy, Hammond, Chris, Hardcastle, Alison, Harding, Simon, Hogg, Ruth, Hysi, Pirro, Keane, Pearse A., Khaw, Peng Tee, Khawaja, Anthony, Lascaratos, Gerassimos, Littlejohns, Thomas, Lotery, Andrew, Luthert, Phil, MacGillivray, Tom, Mackie, Sarah, McGuinness, Bernadette, McKay, Gareth, McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James, Muthy, Zaynah, O'Sullivan, Eoin, Owen, Chris, Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Pontikos, Nikolas, Rahi, Jugnoo, Rudnicka, Alicja, Self, Jay, Sergouniotis, Panagiotis, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Tapp, Robyn, Thaung, Caroline, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vernon, Stephen, Viswanathan, Ananth, Williams, Katie, Woodside, Jayne, Yates, Max, Yip, Jennifer, Zheng, Yalin, Clark, Rosie, Lee, Samantha Sze-Yee, Du, Ran, Wang, Yining, Kneepkens, Sander C.M., Charng, Jason, Huang, Yu, Hunter, Michael L., Jiang, Chen, Tideman, J.Willem L., Melles, Ronald B., Klaver, Caroline C.W., Choquet, Hélène, and Ohno-Matsui, Kyoko

Published
2023
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10. The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 in a pooled analysis of 16,024 men from 22 studies

Author

Watts, Eleanor L, Perez‐Cornago, Aurora, Appleby, Paul N, Albanes, Demetrius, Ardanaz, Eva, Black, Amanda, Bueno‐de‐Mesquita, H Bas, Chan, June M, Chen, Chu, Chubb, SA Paul, Cook, Michael B, Deschasaux, Mélanie, Donovan, Jenny L, English, Dallas R, Flicker, Leon, Freedman, Neal D, Galan, Pilar, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Habel, Laurel A, Häggström, Christel, Haiman, Christopher, Hamdy, Freddie C, Hercberg, Serge, Holly, Jeff M, Huang, Jiaqi, Huang, Wen‐Yi, Johansson, Mattias, Kaaks, Rudolf, Kubo, Tatsuhiko, Lane, J Athene, Layne, Tracy M, Le Marchand, Loic, Martin, Richard M, Metter, E Jeffrey, Mikami, Kazuya, Milne, Roger L, Morris, Howard A, Mucci, Lorelei A, Neal, David E, Neuhouser, Marian L, Oliver, Steven E, Overvad, Kim, Ozasa, Kotaro, Pala, Valeria, Pernar, Claire H, Pollak, Michael, Rowlands, Mari‐Anne, Schaefer, Catherine A, Schenk, Jeannette M, Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Touvier, Mathilde, Trichopoulou, Antonia, Tsilidis, Konstantinos K, Van Den Eeden, Stephen K, Weinstein, Stephanie J, Wilkens, Lynne, Yeap, Bu B, Key, Timothy J, Allen, Naomi E, and Travis, Ruth C

Subjects
Cancer, Aging, Urologic Diseases, Adult, Aged, Aged, 80 and over, Anthropometry, Biomarkers, Tumor, Cross-Sectional Studies, Humans, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Male, Middle Aged, Neoplasms, Prospective Studies, Young Adult, IGFs, IGFBPs, pooled analysis, correlates, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

Published
2019

11. Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank

Author

Wagner, Siegfried Karl, primary, Bountziouka, Vasiliki, additional, Hysi, Pirro, additional, Rahi, Jugnoo Sangeeta, additional, Allen, Naomi, additional, Aslam, Tariq, additional, Atan, Denize, additional, Balaskas, Konstantinos, additional, Barman, Sarah, additional, Barrett, Jenny, additional, Bishop, Paul, additional, Black, Graeme, additional, Braithwaite, Tasanee, additional, Carare, Roxana, additional, Chakravarthy, Usha, additional, Chan, Michelle, additional, Chua, Sharon, additional, Day, Alexander, additional, Desai, Parul, additional, Dhillon, Bal, additional, Dick, Andrew, additional, Doney, Alexander, additional, Egan, Cathy, additional, Ennis, Sarah, additional, Foster, Paul, additional, Fruttiger, Marcus, additional, Gallacher, John, additional, Garway-heath, David (Ted), additional, Gibson, Jane, additional, Guggenheim, Jeremy, additional, Hammond, Chris, additional, Hardcastle, Alison, additional, Harding, Simon, additional, Hogg, Ruth, additional, Keane, Pearse, additional, Tee Khaw, Sir Peng, additional, Khawaja, Anthony, additional, Lascaratos, Gerassimos, additional, Littlejohns, Thomas, additional, Lotery, Andrew, additional, Luben, Robert, additional, Luthert, Phil, additional, Macgillivray, Tom, additional, Mackie, Sarah, additional, Madhusudhan, Savita, additional, Mcguinness, Bernadette, additional, Mckay, Gareth, additional, Mckibbin, Martin, additional, Moore, Tony, additional, Morgan, James, additional, O'sullivan, Eoin, additional, Oram, Richard, additional, Owen, Chris, additional, Patel, Praveen, additional, Paterson, Euan, additional, Peto, Tunde, additional, Petzold, Axel, additional, Pontikos, Nikolas, additional, Rahi, Jugnoo, additional, Rudnicka, Alicja, additional, Sattar, Naveed, additional, Self, Jay, additional, Sergouniotis, Panagiotis, additional, Sivaprasad, Sobha, additional, Steel, David, additional, Stratton, Irene, additional, Strouthidis, Nicholas, additional, Sudlow, Cathie, additional, Sun, Zihan, additional, Tapp, Robyn, additional, Thomas, Dhanes, additional, Trucco, Emanuele, additional, Tufail, Adnan, additional, Viswanathan, Ananth, additional, Vitart, Veronique, additional, Weedon, Mike, additional, Williams, Katie, additional, Williams, Cathy, additional, Woodside, Jayne, additional, Yates, Max, additional, Zheng, Yalin, additional, and Thomas, Mervyn, additional

Published
2024
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13. SARS-CoV-2 is associated with changes in brain structure in UK Biobank

Author

Douaud, Gwenaëlle, Lee, Soojin, Alfaro-Almagro, Fidel, Arthofer, Christoph, Wang, Chaoyue, McCarthy, Paul, Lange, Frederik, Andersson, Jesper L. R., Griffanti, Ludovica, Duff, Eugene, Jbabdi, Saad, Taschler, Bernd, Keating, Peter, Winkler, Anderson M., Collins, Rory, Matthews, Paul M., Allen, Naomi, Miller, Karla L., Nichols, Thomas E., and Smith, Stephen M.

Published
2022
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14. A collaborative analysis of individual participant data from 19 prospective studies assesses circulating vitamin D and prostate cancer risk

Author

Travis, Ruth C, Perez-Cornago, Aurora, Appleby, Paul N, Albanes, Demetrius, Joshu, Corinne E, Lutsey, Pamela L, Mondul, Alison M, Platz, Elizabeth A, Weinstein, Stephanie J, Layne, Tracy M, Helzlsouer, Kathy J, Visvanathan, Kala, Palli, Domenico, Peeters, Petra H, Bueno-de-Mesquita, Bas, Trichopoulou, Antonia, Gunter, Marc J, Tsilidis, Konstantinos K, Sánchez, Maria-Jose, Olsen, Anja, Brenner, Hermann, Schöttker, Ben, Perna, Laura, Holleczek, Bernd, Knekt, Paul, Rissanen, Harri, Yeap, Bu B, Flicker, Leon, Almeida, Osvaldo P, Wong, Yuen Yee Elizabeth, Chan, June M, Giovannucci, Edward L, Stampfer, Meir J, Ursin, Giske, Gislefoss, Randi E, Bjørge, Tone, Meyer, Haakon E, Blomhoff, Rune, Tsugane, Shoichiro, Sawada, Norie, English, Dallas R, Eyles, Darryl W, Heath, Alicia K, Williamson, Elizabeth J, Manjer, Jonas, Malm, Johan, Almquist, Martin, Marchand, Loic Le, Haiman, Christopher A, Wilkens, Lynne R, Schenk, Jeannette M, Tangen, Cathy M, Black, Amanda, Cook, Michael B, Huang, Wen-Yi, Ziegler, Regina G, Martin, Richard M, Hamdy, Freddie C, Donovan, Jenny L, Neal, David E, Touvier, Mathilde, Hercberg, Serge, Galan, Pilar, Deschasaux, Mélanie, Key, Timothy J, and Allen, Naomi E

Subjects
Clinical Trials and Supportive Activities, Nutrition, Cancer, Prostate Cancer, Urologic Diseases, Prevention, Aging, Clinical Research, Aged, Case-Control Studies, Cross-Sectional Studies, Humans, Male, Middle Aged, Odds Ratio, Prospective Studies, Prostatic Neoplasms, Risk Assessment, Risk Factors, Vitamin D, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; P trend < 0.001). However, this association varied by disease aggressiveness (P heterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.

Published
2019

15. Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies

Author

Watts, Eleanor L, Appleby, Paul N, Perez-Cornago, Aurora, Bueno-de-Mesquita, H Bas, Chan, June M, Chen, Chu, Cohn, Barbara A, Cook, Michael B, Flicker, Leon, Freedman, Neal D, Giles, Graham G, Giovannucci, Edward, Gislefoss, Randi E, Hankey, Graeme J, Kaaks, Rudolf, Knekt, Paul, Kolonel, Laurence N, Kubo, Tatsuhiko, Le Marchand, Loïc, Luben, Robert N, Luostarinen, Tapio, Männistö, Satu, Metter, E Jeffrey, Mikami, Kazuya, Milne, Roger L, Ozasa, Kotaro, Platz, Elizabeth A, Quirós, J Ramón, Rissanen, Harri, Sawada, Norie, Stampfer, Meir, Stanczyk, Frank Z, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine M, Thompson, Ian M, Tsilidis, Konstantinos K, Tsugane, Shoichiro, Ursin, Giske, Vatten, Lars, Weiss, Noel S, Yeap, Bu B, Allen, Naomi E, Key, Timothy J, and Travis, Ruth C

Subjects
Cancer, Clinical Research, Prevention, Urologic Diseases, Prostate Cancer, Aging, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Biomarkers, Case-Control Studies, Down-Regulation, Humans, Male, Middle Aged, Neoplasm Grading, Prospective Studies, Prostatic Neoplasms, Protective Factors, Risk Assessment, Risk Factors, Testosterone, Time Factors, Androgens Pooled analysis, Prospective studies, Prostate cancer, Sex hormones, Epidemiology, Androgens, Pooled analysis, Clinical Sciences, Urology & Nephrology
Abstract

BackgroundExperimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.ObjectiveTo examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.Design, setting, and participantsAnalysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.Outcome measurements and statistical analysisOdds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.Results and limitationsMen in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p

Published
2018

18. Periodontitis and outer retinal thickness: A cross-sectional analysis of the UK Biobank cohort

Author

Wagner, Siegfried K., primary, Patel, Praveen J., additional, Huemer, Josef, additional, Khalid, Hagar, additional, Stuart, Kelsey V., additional, Chu, Colin J., additional, Williamson, Dominic J., additional, Struyven, Robbert R., additional, Romero-Bascones, David, additional, Foster, Paul J., additional, Khawaja, Anthony P., additional, Petzold, Axel, additional, Balaskas, Konstantinos, additional, Cortina-Borja, Mario, additional, Chapple, Iain, additional, Dietrich, Thomas, additional, Rahi, Jugnoo S., additional, Denniston, Alastair K., additional, Keane, Pearse A., additional, Allen, Naomi, additional, Aslam, Tariq, additional, Atan, Denize, additional, Balaskas, Konsantinos, additional, Barman, Sarah A., additional, Barrett, Jenny H., additional, Bishop, Paul, additional, Black, Graeme, additional, Braithwaite, Tasanee, additional, Carare, Roxana O., additional, Chakravarthy, Usha, additional, Chan, Michelle, additional, Chua, Sharon Y.L., additional, Day, Alexander, additional, Desai, Parul, additional, Dhillon, Bal, additional, Dick, Andrew D., additional, Doney, Alexander, additional, Egan, Cathy, additional, Ennis, Sarah, additional, Foster, Paul, additional, Fruttiger, Marcus, additional, Gallacher, John E.J., additional, Garway-Heath, David F., additional, Gibson, Jane, additional, Guggenheim, Jeremy A., additional, Hammond, Chris J., additional, Hardcastle, Alison, additional, Harding, Simon P., additional, Hogg, Ruth E., additional, Hysi, Pirro, additional, Khaw, Sir Peng T., additional, Lascaratos, Gerassimos, additional, Littlejohns, Thoams, additional, Lotery, Andrew J., additional, Luben, Robert, additional, Luthert, Phil, additional, Macgillivray, Tom, additional, Mackie, Sarah, additional, McGuinness, Bernadette, additional, McKay, Gareth J., additional, McKibbin, Martin, additional, Moore, Tony, additional, Morgan, James E., additional, O’Sullivan, Eoin, additional, Oram, Richard, additional, Owen, Chris G., additional, Patel, Praveen, additional, Paterson, Euan, additional, Peto, Tunde, additional, Rudnikca, Alicja R., additional, Sattar, Naveed, additional, Self, Jay, additional, Sergouniotis, Panagiotis, additional, Sivaprasad, Sobha, additional, Steel, David, additional, Stratton, Irene, additional, Strouthidis, Nicholas, additional, Sudlow, Cathie, additional, Sun, Zihan, additional, Tapp, Robyn, additional, Thomas, Dhanes, additional, Trucco, Emanuele, additional, Tufail, Adnan, additional, Vitart, Veronique, additional, Viswanathan, Ananth C., additional, Weedon, Mike, additional, Williams, Cathy, additional, Williams, Katie, additional, Woodside, Jayne V., additional, Yates, MaxM., additional, Yip, Jennifer, additional, and Zheng, Yalin, additional

Published
2024
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20. Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men

Author

Watts, Eleanor L, Appleby, Paul N, Albanes, Demetrius, Black, Amanda, Chan, June M, Chen, Chu, Cirillo, Piera M, Cohn, Barbara A, Cook, Michael B, Donovan, Jenny L, Ferrucci, Luigi, Garland, Cedric F, Giles, Graham G, Goodman, Phyllis J, Habel, Laurel A, Haiman, Christopher A, Holly, Jeff MP, Hoover, Robert N, Kaaks, Rudolf, Knekt, Paul, Kolonel, Laurence N, Kubo, Tatsuhiko, Le Marchand, Loïc, Luostarinen, Tapio, MacInnis, Robert J, Mäenpää, Hanna O, Männistö, Satu, Metter, E Jeffrey, Milne, Roger L, Nomura, Abraham MY, Oliver, Steven E, Parsons, J Kellogg, Peeters, Petra H, Platz, Elizabeth A, Riboli, Elio, Ricceri, Fulvio, Rinaldi, Sabina, Rissanen, Harri, Sawada, Norie, Schaefer, Catherine A, Schenk, Jeannette M, Stanczyk, Frank Z, Stampfer, Meir, Stattin, Pär, Stenman, Ulf-Håkan, Tjønneland, Anne, Trichopoulou, Antonia, Thompson, Ian M, Tsugane, Shoichiro, Vatten, Lars, Whittemore, Alice S, Ziegler, Regina G, Allen, Naomi E, Key, Timothy J, and Travis, Ruth C

Subjects
Cancer, Aging, Estrogen, Good Health and Well Being, Adult, Anthropometry, Behavior, Datasets as Topic, Gonadal Steroid Hormones, Humans, Male, Social Class, Young Adult, General Science & Technology
Abstract

IntroductionSex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.MethodsStatistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.ResultsOlder age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.ConclusionCirculating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Published
2017

22. A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Author

Travis, Ruth C, Appleby, Paul N, Martin, Richard M, Holly, Jeff MP, Albanes, Demetrius, Black, Amanda, Bueno-de-Mesquita, HB As, Chan, June M, Chen, Chu, Chirlaque, Maria-Dolores, Cook, Michael B, Deschasaux, Mélanie, Donovan, Jenny L, Ferrucci, Luigi, Galan, Pilar, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Habel, Laurel A, Hamdy, Freddie C, Helzlsouer, Kathy J, Hercberg, Serge, Hoover, Robert N, Janssen, Joseph AMJL, Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Metter, E Jeffrey, Mikami, Kazuya, Morris, Joan K, Neal, David E, Neuhouser, Marian L, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth A, Pollak, Michael, Price, Alison J, Roobol, Monique J, Schaefer, Catherine, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine M, Touvier, Mathilde, Wald, Nicholas J, Weiss, Noel S, Ziegler, Regina G, Key, Timothy J, and Allen, Naomi E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Prostate Cancer, Cancer, Urologic Diseases, Aged, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, Prostatic Neoplasms, Risk Factors, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.

Published
2016

23. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies 1–3

Author

Key, Timothy J, Appleby, Paul N, Travis, Ruth C, Albanes, Demetrius, Alberg, Anthony J, Barricarte, Aurelio, Black, Amanda, Boeing, Heiner, Bueno-de-Mesquita, H Bas, Chan, June M, Chen, Chu, Cook, Michael B, Donovan, Jenny L, Galan, Pilar, Gilbert, Rebecca, Giles, Graham G, Giovannucci, Edward, Goodman, Gary E, Goodman, Phyllis J, Gunter, Marc J, Hamdy, Freddie C, Heliövaara, Markku, Helzlsouer, Kathy J, Henderson, Brian E, Hercberg, Serge, Hoffman-Bolton, Judy, Hoover, Robert N, Johansson, Mattias, Khaw, Kay-Tee, King, Irena B, Knekt, Paul, Kolonel, Laurence N, Le Marchand, Loic, Männistö, Satu, Martin, Richard M, Meyer, Haakon E, Mondul, Alison M, Moy, Kristin A, Neal, David E, Neuhouser, Marian L, Palli, Domenico, Platz, Elizabeth A, Pouchieu, Camille, Rissanen, Harri, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Tjønneland, Anne, Touvier, Mathilde, Trichopoulou, Antonia, Weinstein, Stephanie J, Ziegler, Regina G, Zhou, Cindy Ke, Allen, Naomi E, Biomarkers, Endogenous Hormones Nutritional, and Group, Prostate Cancer Collaborative

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Urologic Diseases, Nutrition, Prostate Cancer, Cancer, Aging, Clinical Research, Adult, Biomarkers, Carotenoids, Case-Control Studies, Cohort Studies, Cross-Sectional Studies, Humans, Lycopene, Male, Meta-Analysis as Topic, Middle Aged, Neoplasm Grading, Neoplasm Staging, Observational Studies as Topic, Prospective Studies, Prostate, Prostatic Neoplasms, Risk Factors, Vitamin A, alpha-Tocopherol, prostate cancer, carotenoids, retinol, tocopherols, vitamin E, vitamin A, pooled analysis, nested case-control study, biomarkers, Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

BackgroundIndividual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.ObjectiveThe objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.DesignPrincipal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.ResultsData were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk.ConclusionsOverall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.

Published
2015

24. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Wang, Zhaoming, Zhu, Bin, Zhang, Mingfeng, Parikh, Hemang, Jia, Jinping, Chung, Charles C, Sampson, Joshua N, Hoskins, Jason W, Hutchinson, Amy, Burdette, Laurie, Ibrahim, Abdisamad, Hautman, Christopher, Raj, Preethi S, Abnet, Christian C, Adjei, Andrew A, Ahlbom, Anders, Albanes, Demetrius, Allen, Naomi E, Ambrosone, Christine B, Aldrich, Melinda, Amiano, Pilar, Amos, Christopher, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L, Arici, Cecilia, Arslan, Alan A, Austin, Melissa A, Baris, Dalsu, Barkauskas, Donald A, Bassig, Bryan A, Beane Freeman, Laura E, Berg, Christine D, Berndt, Sonja I, Bertazzi, Pier Alberto, Biritwum, Richard B, Black, Amanda, Blot, William, Boeing, Heiner, Boffetta, Paolo, Bolton, Kelly, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Brennan, Paul, Brinton, Louise A, Brotzman, Michelle, Bueno-de-Mesquita, H Bas, Buring, Julie E, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Cao, Guangwen, Caporaso, Neil E, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chang, Gee-Chen, Chang, I-Shou, Chang-Claude, Jenny, Che, Xu, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chung-Hsing, Chen, Constance, Chen, Kuan-Yu, Chen, Yuh-Min, Chokkalingam, Anand P, Chu, Lisa W, Clavel-Chapelon, Francoise, Colditz, Graham A, Colt, Joanne S, Conti, David, Cook, Michael B, Cortessis, Victoria K, Crawford, E David, Cussenot, Olivier, Davis, Faith G, De Vivo, Immaculata, Deng, Xiang, Ding, Ti, Dinney, Colin P, Di Stefano, Anna Luisa, Diver, W Ryan, Duell, Eric J, Elena, Joanne W, Fan, Jin-Hu, Feigelson, Heather Spencer, Feychting, Maria, Figueroa, Jonine D, Flanagan, Adrienne M, Fraumeni, Joseph F, Freedman, Neal D, Fridley, Brooke L, Fuchs, Charles S, Gago-Dominguez, Manuela, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M, and Garcia-Closas, Montserrat

Subjects
Biological Sciences, Genetics, Cancer, Clinical Research, Human Genome, Prevention, Aetiology, 2.1 Biological and endogenous factors, Alleles, Chromosomes, Human, Pair 5, Computational Biology, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Membrane Proteins, Neoplasm Proteins, Neoplasms, Odds Ratio, Polymorphism, Single Nucleotide, Risk, Telomerase, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Published
2014

25. Association between metabolic syndrome and risk of incident dementia in UK Biobank.

Author

Qureshi, Danial, Collister, Jennifer, Allen, Naomi E., Kuźma, Elżbieta, and Littlejohns, Thomas

Abstract

INTRODUCTION: The association between metabolic syndrome (MetS) and incident dementia remains inconclusive. METHODS: In 176,249 dementia‐free UK Biobank participants aged ≥60 years at baseline, Cox proportional‐hazards models were used to investigate the association between MetS and incident dementia. MetS was defined as the presence of ≥3 of the following: elevated waist circumference, triglycerides, blood pressure, blood glucose, and reduced high‐density lipoprotein cholesterol. RESULTS: Over 15 years of follow‐up (median = 12.3), 5255 participants developed dementia. MetS was associated with an increased risk of incident dementia (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.06, 1.18). The association remained consistent when restricting to longer follow‐up intervals: >5 to 10 years (HR: 1.17, 95% CI: 1.07, 1.27) and >10 years (HR: 1.22, 95% CI: 1.12, 1.32). Stronger associations were observed in those with ≥4 MetS components and in apolipoprotein‐E (APOE)‐ε4 non‐carriers. DISCUSSION: In this large population‐based prospective cohort, MetS was associated with an increased risk of dementia. Highlights: MetS was associated with a 12% increased risk of incident all‐cause dementia.Associations remained similar after restricting the analysis to those with longer follow‐up.The presence of four or five MetS components was significantly associated with dementia.Stronger associations were observed in those with a low genetic risk for dementia. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium

Author

Elena, Joanne W, Steplowski, Emily, Yu, Kai, Hartge, Patricia, Tobias, Geoffrey S, Brotzman, Michelle J, Chanock, Stephen J, Stolzenberg-Solomon, Rachael Z, Arslan, Alan A, Bueno-de-Mesquita, H Bas, Helzlsouer, Kathy, Jacobs, Eric J, LaCroix, Andrea, Petersen, Gloria, Zheng, Wei, Albanes, Demetrius, Allen, Naomi E, Amundadottir, Laufey, Bao, Ying, Boeing, Heiner, Boutron-Ruault, Marie-Christine, Buring, Julie E, Gaziano, J Michael, Giovannucci, Edward L, Duell, Eric J, Hallmans, Göran, Howard, Barbara V, Hunter, David J, Hutchinson, Amy, Jacobs, Kevin B, Kooperberg, Charles, Kraft, Peter, Mendelsohn, Julie B, Michaud, Dominique S, Palli, Domenico, Phillips, Lawrence S, Overvad, Kim, Patel, Alpa V, Sansbury, Leah, Shu, Xiao-Ou, Simon, Michael S, Slimani, Nadia, Trichopoulos, Dimitrios, Visvanathan, Kala, Virtamo, Jarmo, Wolpin, Brian M, Zeleniuch-Jacquotte, Anne, Fuchs, Charles S, Hoover, Robert N, and Gross, Myron

Subjects
Biomedical and Clinical Sciences, Epidemiology, Health Services and Systems, Health Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Pancreatic Cancer, Prevention, Digestive Diseases, Clinical Research, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Diabetes Complications, Diabetes Mellitus, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Risk Factors, Public Health and Health Services, Oncology and carcinogenesis
Abstract

PurposeDiabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan).MethodsThe pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (

Published
2013

29. Cohort profile:rationale and methods of UK Biobank repeat imaging study eye measures to study dementia

Author

Foster, Paul J., Atan, Denize, Khawaja, Anthony, Lotery, Andrew, MacGillivray, Tom, Owen, Christopher G., Patel, Praveen J., Petzold, Axel, Rudnicka, Alicja, Sun, Zihan, Sheard, Simon, and Allen, Naomi

Abstract

PURPOSE: The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study. PARTICIPANTS: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs. FINDINGS TO DATE: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes. FUTURE PLANS: The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.

Published
2023

30. The UK Biobank resource with deep phenotyping and genomic data

Author

Bycroft, Clare, Freeman, Colin, Petkova, Desislava, Band, Gavin, Elliott, Lloyd T., Sharp, Kevin, Motyer, Allan, Vukcevic, Damjan, Delaneau, Olivier, O’Connell, Jared, Cortes, Adrian, Welsh, Samantha, Young, Alan, Effingham, Mark, McVean, Gil, Leslie, Stephen, Allen, Naomi, Donnelly, Peter, and Marchini, Jonathan

Published
2018
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31. MEMS sensors for wall shear stress and flow vector measurement

Author

Allen, Naomi

Subjects
624.177650153362
Abstract

The accurate measurement of airflows is an important area of experimental aerodynamics. MEMS technology has been applied to the measurement of wall shear stress and freestream velocity vectors. Existing methods of measuring wall shear stress vary greatly and have different strengths and weaknesses, making them each applicable to specific situations. Probes designed for measuring 3D velocity components are relatively large in diameter, introducing significant disturbances into the airflow. The tip diameters of such probes are typically of the order of several millimetres and the minimum diameter is around 1 mm. A sensor for measuring wall shear stress, consisting of a surface fence structure 5 mm long, 750 μm high and 20 μm thick was developed. The fence, and main body on which it was mounted, were fabricated from the photo-definable polymer SU8 with an integrated gold resistive strain gauge to measure the pressure-induced deflection. Wind tunnel testing gave a voltage output of 0.18 mV for a shear stress of approximately 0.35 Pa. This concept was then adapted and an in-plane cantilever sensor was developed. The cantilever sensor was manufactured from SU-8 with an integrated resistive strain gauge of NiCr. The pressure-induced deflection of the cantilever, calibrated by the integrated strain gauge, could be related to the wall shear stress on the surface. The sensor gave a response of 9.6x10(^-4) (mV/V) μm under mechanical deflection. For a 2 mm long, 400 μm wide cantilever when tested on a flat plate in a wind tunnel, a response of 1 mV for a shear stress of 0.35 Pa was seen. Four cantilever sensors were arranged orthogonally to create a new type of probe for measuring flow direction and velocity, which could also measure total pressure. The probe was shown to be able to measure these variables and with further development had the potential to allow the fabrication of a smaller probe tip than that possible by conventional methods.

Published
2008

32. Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial

Author

Wang, Xiaoxia, Mobley, Alastair R, Tica, Otilia, Okoth, Kelvin, Ghosh, Rebecca E, Myles, Puja, Williams, Tim, Haynes, Sandra, Nirantharakumar, Krishnarajah, Shukla, David, Kotecha, Dipak, Beatty, Susan, Mehta, Samir, Breeze, Sophie, Lancaster, Karen, Fordyce, Stuart, Allen, Naomi, Calvert, Melanie, Denniston, Alastair, Gkoutos, George, Jayawardana, Sahan, Ball, Simon, Baigent, Colin, Brocklehurst, Peter, Lester, Will, McManus, Richard, Seri, Stefano, Valentine, Janet, Camm, A John, Moore, Dame Julie, Rogers, Amy, Stanbury, Mary, Flather, Marcus, Walker, Suzy, and Wang, Duolao

Abstract

Aims Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research. Methods and results The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and ‘no-visit’ follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality). Conclusion Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk.

Published
2022

33. Variant ABO Blood Group Alleles, Secretor Status, and Risk of Pancreatic Cancer: Results from the Pancreatic Cancer Cohort Consortium

Author

Wolpin, Brian M, Kraft, Peter, Xu, Mousheng, Steplowski, Emily, Olsson, Martin L, Arslan, Alan A, Bueno-de-Mesquita, H Bas, Gross, Myron, Helzlsouer, Kathy, Jacobs, Eric J, LaCroix, Andrea, Petersen, Gloria, Stolzenberg-Solomon, Rachael Z, Zheng, Wei, Albanes, Demetrius, Allen, Naomi E, Amundadottir, Laufey, Austin, Melissa A, Boutron-Ruault, Marie-Christine, Buring, Julie E, Canzian, Federico, Chanock, Stephen J, Gaziano, J Michael, Giovannucci, Edward L, Hallmans, Göran, Hankinson, Susan E, Hoover, Robert N, Hunter, David J, Hutchinson, Amy, Jacobs, Kevin B, Kooperberg, Charles, Mendelsohn, Julie B, Michaud, Dominique S, Overvad, Kim, Patel, Alpa V, Sanchéz, Maria-José, Sansbury, Leah, Shu, Xiao-Ou, Slimani, Nadia, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vineis, Paolo, Visvanathan, Kala, Virtamo, Jarmo, Wactawski-Wende, Jean, Watters, Joanne, Yu, Kai, Zeleniuch-Jacquotte, Anne, Hartge, Patricia, and Fuchs, Charles S

Subjects
Digestive Diseases, Cancer, Clinical Research, Genetics, Rare Diseases, Pancreatic Cancer, Prevention, Human Genome, Aetiology, 2.1 Biological and endogenous factors, ABO Blood-Group System, Alleles, Cohort Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Glycosyltransferases, Humans, Odds Ratio, Pancreatic Neoplasms, Phenotype, Polymorphism, Single Nucleotide, Medical and Health Sciences, Epidemiology
Abstract

BackgroundSubjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A(1) versus A(2) variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A(1) allele would confer greater risk than A(2) allele, 2) protective effect of the O allele would be equivalent for O01 and O02 variants, 3) secretor phenotype would modify the association with risk.MethodsWe determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1,533 cases and 1,582 controls from 12 prospective cohort studies. Adjusted odds ratios (OR) for pancreatic cancer were calculated using logistic regression.ResultsAn increased risk was observed in participants with A(1) but not A(2) alleles. Compared with subjects with genotype O/O, genotypes A(2)/O, A(2)/A(1), A(1)/O, and A(1)/A(1) had ORs of 0.96 (95% CI, 0.72-1.26), 1.46 (95% CI, 0.98-2.17), 1.48 (95% CI, 1.23-1.78), and 1.71 (95% CI, 1.18-2.47). Risk was similar for O01 and O02 variant O alleles. Compared with O01/O01, the ORs for each additional allele of O02, A(1), and A(2) were 1.00 (95% CI, 0.87-1.14), 1.38 (95% CI, 1.20-1.58), and 0.96 (95% CI, 0.77-1.20); P, O01 versus O02 = 0.94, A(1) versus A(2) = 0.004. Secretor phenotype was not an effect modifier (P-interaction = 0.63).ConclusionsAmong participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk.ImpactThese data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34.

Published
2010

34. Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).

Author

Jacobs, Eric J, Chanock, Stephen J, Fuchs, Charles S, Lacroix, Andrea, McWilliams, Robert R, Steplowski, Emily, Stolzenberg-Solomon, Rachael Z, Arslan, Alan A, Bueno-de-Mesquita, H Bas, Gross, Myron, Helzlsouer, Kathy, Petersen, Gloria, Zheng, Wei, Agalliu, Ilir, Allen, Naomi E, Amundadottir, Laufey, Boutron-Ruault, Marie-Christine, Buring, Julie E, Canzian, Federico, Clipp, Sandra, Dorronsoro, Miren, Gaziano, J Michael, Giovannucci, Edward L, Hankinson, Susan E, Hartge, Patricia, Hoover, Robert N, Hunter, David J, Jacobs, Kevin B, Jenab, Mazda, Kraft, Peter, Kooperberg, Charles, Lynch, Shannon M, Sund, Malin, Mendelsohn, Julie B, Mouw, Tracy, Newton, Christina C, Overvad, Kim, Palli, Domenico, Peeters, Petra HM, Rajkovic, Aleksandar, Shu, Xiao-Ou, Thomas, Gilles, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Virtamo, Jarmo, Wactawski-Wende, Jean, Wolpin, Brian M, Yu, Kai, and Zeleniuch-Jacquotte, Anne

Subjects
Humans, Pancreatic Neoplasms, Genetic Predisposition to Disease, Case-Control Studies, Cohort Studies, Genome-Wide Association Study, Colo-Rectal Cancer, Clinical Research, Rare Diseases, Aging, Cancer, Digestive Diseases, Prostate Cancer, Ovarian Cancer, Pancreatic Cancer, Breast Cancer, Prevention, Urologic Diseases, 2.1 Biological and endogenous factors, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19-2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12-1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52-1.31), breast cancer (OR = 1.21, 95% CI = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93-1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.

Published
2010

35. Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan)

Author

Michaud, Dominique S, Vrieling, Alina, Jiao, Li, Mendelsohn, Julie B, Steplowski, Emily, Lynch, Shannon M, Wactawski-Wende, Jean, Arslan, Alan A, Bas Bueno-de-Mesquita, H, Fuchs, Charles S, Gross, Myron, Helzlsouer, Kathy, Jacobs, Eric J, LaCroix, Andrea, Petersen, Gloria, Zheng, Wei, Allen, Naomi, Ammundadottir, Laufey, Bergmann, Manuela M, Boffetta, Paolo, Buring, Julie E, Canzian, Federico, Chanock, Stephen J, Clavel-Chapelon, Françoise, Clipp, Sandra, Freiberg, Matthew S, Michael Gaziano, J, Giovannucci, Edward L, Hankinson, Susan, Hartge, Patricia, Hoover, Robert N, Allan Hubbell, F, Hunter, David J, Hutchinson, Amy, Jacobs, Kevin, Kooperberg, Charles, Kraft, Peter, Manjer, Jonas, Navarro, Carmen, Peeters, Petra HM, Shu, Xiao-Ou, Stevens, Victoria, Thomas, Gilles, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Tumino, Rosario, Vineis, Paolo, Virtamo, Jarmo, Wallace, Robert, Wolpin, Brian M, Yu, Kai, Zeleniuch-Jacquotte, Anne, and Stolzenberg-Solomon, Rachael Z

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Alcoholism, Alcohol Use and Health, Cancer, Digestive Diseases, Pancreatic Cancer, Rare Diseases, Clinical Research, Substance Misuse, Oral and gastrointestinal, Good Health and Well Being, Aged, Alcohol Drinking, Case-Control Studies, Cohort Studies, Female, Humans, Male, Pancreatic Neoplasms, Prospective Studies, Alcohol, Pancreatic cancer, Pooled analysis, Oncology and Carcinogenesis, Public Health and Health Services, Epidemiology, Oncology and carcinogenesis
Abstract

The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. >0 to

Published
2010

36. Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium.

Author

Wolpin, Brian M, Kraft, Peter, Gross, Myron, Helzlsouer, Kathy, Bueno-de-Mesquita, H Bas, Steplowski, Emily, Stolzenberg-Solomon, Rachael Z, Arslan, Alan A, Jacobs, Eric J, Lacroix, Andrea, Petersen, Gloria, Zheng, Wei, Albanes, Demetrius, Allen, Naomi E, Amundadottir, Laufey, Anderson, Garnet, Boutron-Ruault, Marie-Christine, Buring, Julie E, Canzian, Federico, Chanock, Stephen J, Clipp, Sandra, Gaziano, John Michael, Giovannucci, Edward L, Hallmans, Göran, Hankinson, Susan E, Hoover, Robert N, Hunter, David J, Hutchinson, Amy, Jacobs, Kevin, Kooperberg, Charles, Lynch, Shannon M, Mendelsohn, Julie B, Michaud, Dominique S, Overvad, Kim, Patel, Alpa V, Rajkovic, Aleksandar, Sanchéz, Maria-José, Shu, Xiao-Ou, Slimani, Nadia, Thomas, Gilles, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vineis, Paolo, Virtamo, Jarmo, Wactawski-Wende, Jean, Yu, Kai, Zeleniuch-Jacquotte, Anne, Hartge, Patricia, and Fuchs, Charles S

Subjects
Humans, Pancreatic Neoplasms, Genetic Predisposition to Disease, ABO Blood-Group System, Logistic Models, Odds Ratio, Risk Factors, Cohort Studies, Gene Frequency, Genotype, Alleles, Aged, Middle Aged, Female, Male, Clinical Research, Genetics, Pancreatic Cancer, Rare Diseases, Digestive Diseases, Cancer, Prevention, 2.1 Biological and endogenous factors, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk.

Published
2010

39. A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Author

Clark, Rosie, primary, Lee, Samantha Sze-Yee, additional, Du, Ran, additional, Wang, Yining, additional, Kneepkens, Sander C.M., additional, Charng, Jason, additional, Huang, Yu, additional, Hunter, Michael L., additional, Jiang, Chen, additional, Tideman, J.Willem L., additional, Melles, Ronald B., additional, Klaver, Caroline C.W., additional, Mackey, David A., additional, Williams, Cathy, additional, Choquet, Hélène, additional, Ohno-Matsui, Kyoko, additional, Guggenheim, Jeremy A., additional, Bailey-Wilson, Joan E., additional, Baird, Paul N., additional, Barathi, Veluchamy A., additional, Biino, Ginevra, additional, Burdon, Kathryn P., additional, Campbell, Harry, additional, Chen, Li Jia, additional, Cheng, Ching-Yu, additional, Chew, Emily Y., additional, Craig, Jamie E., additional, Deangelis, Margaret M., additional, Delcourt, Cécile, additional, Ding, Xiaohu, additional, Fan, Qiao, additional, Fossarello, Maurizio, additional, Foster, Paul J., additional, Gharahkhani, Puya, additional, Guo, Xiaobo, additional, Haarman, Annechien E.G., additional, Haller, Toomas, additional, Hammond, Christopher J., additional, Han, Xikun, additional, Hayward, Caroline, additional, He, Mingguang, additional, Hewitt, Alex W., additional, Hoang, Quan, additional, Hysi, Pirro G., additional, Iglesias, Adriana I., additional, Igo, Robert P., additional, Iyengar, Sudha K., additional, Jonas, Jost B., additional, Kähönen, Mika, additional, Kaprio, Jaakko, additional, Khawaja, Anthony P., additional, Klein, Barbara E., additional, Lass, Jonathan H., additional, Lee, Kris, additional, Lehtimäki, Terho, additional, Lewis, Deyana, additional, Li, Qing, additional, Li, Shi-Ming, additional, Lyytikäinen, Leo-Pekka, additional, MacGregor, Stuart, additional, Martin, Nicholas G., additional, Meguro, Akira, additional, Metspalu, Andres, additional, Middlebrooks, Candace, additional, Miyake, Masahiro, additional, Mizuki, Nobuhisa, additional, Musolf, Anthony, additional, Nickels, Stefan, additional, Oexle, Konrad, additional, Pang, Chi Pui, additional, Pärssinen, Olavi, additional, Paterson, Andrew D., additional, Pfeiffer, Norbert, additional, Polasek, Ozren, additional, Rahi, Jugnoo S., additional, Raitakari, Olli, additional, Rudan, Igor, additional, Sahebjada, Srujana, additional, Saw, Seang-Mei, additional, Simpson, Claire L., additional, Stambolian, Dwight, additional, Tai, E-Shyong, additional, Tedja, Milly S., additional, Tideman, J. Willem L., additional, Tsujikawa, Akitaka, additional, van Duijn, Cornelia M., additional, Verhoeven, Virginie J.M., additional, Vitart, Veronique, additional, Wang, Ningli, additional, Wang, Ya Xing, additional, Wedenoja, Juho, additional, Wei, Wen Bin, additional, Williams, Katie M., additional, Wilson, James F., additional, Wojciechowski, Robert, additional, Yam, Jason C.S., additional, Yamashiro, Kenji, additional, Yap, Maurice K.H., additional, Yazar, Seyhan, additional, Yip, Shea Ping, additional, Young, Terri L., additional, Zhou, Xiangtian, additional, Allen, Naomi, additional, Aslam, Tariq, additional, Atan, Denize, additional, Barman, Sarah, additional, Barrett, Jenny, additional, Bishop, Paul, additional, Black, Graeme, additional, Bunce, Catey, additional, Carare, Roxana, additional, Chakravarthy, Usha, additional, Chan, Michelle, additional, Chua, Sharon, additional, Cipriani, Valentina, additional, Day, Alexander, additional, Desai, Parul, additional, Dhillon, Bal, additional, Dick, Andrew, additional, Doney, Alexander, additional, Egan, Cathy, additional, Ennis, Sarah, additional, Foster, Paul, additional, Fruttiger, Marcus, additional, Gallacher, John, additional, Garway-Heath, David, additional, Gibson, Jane, additional, Gore, Dan, additional, Guggenheim, Jeremy, additional, Hammond, Chris, additional, Hardcastle, Alison, additional, Harding, Simon, additional, Hogg, Ruth, additional, Hysi, Pirro, additional, Keane, Pearse A., additional, Khaw, Peng Tee, additional, Khawaja, Anthony, additional, Lascaratos, Gerassimos, additional, Littlejohns, Thomas, additional, Lotery, Andrew, additional, Luthert, Phil, additional, MacGillivray, Tom, additional, Mackie, Sarah, additional, McGuinness, Bernadette, additional, McKay, Gareth, additional, McKibbin, Martin, additional, Mitry, Danny, additional, Moore, Tony, additional, Morgan, James, additional, Muthy, Zaynah, additional, O'Sullivan, Eoin, additional, Owen, Chris, additional, Patel, Praveen, additional, Paterson, Euan, additional, Peto, Tunde, additional, Petzold, Axel, additional, Pontikos, Nikolas, additional, Rahi, Jugnoo, additional, Rudnicka, Alicja, additional, Self, Jay, additional, Sergouniotis, Panagiotis, additional, Sivaprasad, Sobha, additional, Steel, David, additional, Stratton, Irene, additional, Strouthidis, Nicholas, additional, Sudlow, Cathie, additional, Tapp, Robyn, additional, Thaung, Caroline, additional, Thomas, Dhanes, additional, Trucco, Emanuele, additional, Tufail, Adnan, additional, Vernon, Stephen, additional, Viswanathan, Ananth, additional, Williams, Katie, additional, Woodside, Jayne, additional, Yates, Max, additional, Yip, Jennifer, additional, and Zheng, Yalin, additional

Published
2023
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42. The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions

Author

Littlejohns, Thomas J., Holliday, Jo, Gibson, Lorna M., Garratt, Steve, Oesingmann, Niels, Alfaro-Almagro, Fidel, Bell, Jimmy D., Boultwood, Chris, Collins, Rory, Conroy, Megan C., Crabtree, Nicola, Doherty, Nicola, Frangi, Alejandro F., Harvey, Nicholas C., Leeson, Paul, Miller, Karla L., Neubauer, Stefan, Petersen, Steffen E., Sellors, Jonathan, Sheard, Simon, Smith, Stephen M., Sudlow, Cathie L. M., Matthews, Paul M., and Allen, Naomi E.

Published
2020
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44. UK biobank: Enhanced assessment of the epidemiology and long-term impact of coronavirus disease-2019

Author

Feng, Qi, primary, Lacey, Ben, additional, Bešević, Jelena, additional, Omiyale, Wemimo, additional, Conroy, Megan, additional, Starkey, Fenella, additional, Calvin, Catherine, additional, Callen, Howard, additional, Bramley, Laura, additional, Welsh, Samantha, additional, Young, Allen, additional, Effingham, Mark, additional, Young, Alan, additional, Collins, Rory, additional, Holliday, Jo, additional, and Allen, Naomi, additional

Published
2023
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46. The association of alcohol consumption with glaucoma and related traits: Findings from the UK Biobank

Author

Stuart, Kelsey, Luben, Robert N., Warwick, Alasdair N., Madjedi, Kian, Patel, Praveen J., Biradar, Mahantesh I., Sun, Zihan, Chia, Mark, Pasquale, Louis, Wiggs, Janey, Kang, Jae H., Kim, Jihye, Aschard, Hugues, Tran, Jessica H., Lentjes, Marleen, Foster, Paul J., Khawaja, Anthony, Chua, Sharon, Do, Ron, Foster, Paul, Kang, Jae, Kastner, Alan, Luben, Robert, Montesano, Giovanni, Warwick, Alasdair, Allen, Naomi, Aslam, Tariq, Atan, Denize, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Black, Graeme, Carare, Roxana, Ennis, Sarah, Gibson, Jane, Lotery, Andrew, Morgan, James, Self, Jay, Stratton, Irene, Chen, Li, Cheng, Ching Yu, Cree, Angela, and Wilson, James

Abstract

Purpose: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. Design: Cross-sectional observational and gene–environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. Participants: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407). Methods: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. Main Outcome Measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell–inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. Results: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 μm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol–IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. Conclusions: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Published
2022

47. UK Biobank: a globally important resource for cancer research

Author

Conroy, Megan C., primary, Lacey, Ben, additional, Bešević, Jelena, additional, Omiyale, Wemimo, additional, Feng, Qi, additional, Effingham, Mark, additional, Sellers, Jonathan, additional, Sheard, Simon, additional, Pancholi, Mahesh, additional, Gregory, Gareth, additional, Busby, John, additional, Collins, Rory, additional, and Allen, Naomi E., additional

Published
2022
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48. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer:a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author

Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, and consortium, The PRACTICAL

Subjects
Cancer och onkologi, prospective analysis, Epidemiology, General Medicine, prostate cancer, aggressive prostate cancer, Cancer and Oncology, Mendelian randomization, international consortia, Insulin-like growth factor-I, ICEP, Bristol Population Health Science Institute
Abstract

Background Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.

Published
2022

50. Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses

Author

Dimou, Niki, primary, Omiyale, Wemimo, additional, Biessy, Carine, additional, Viallon, Vivian, additional, Kaaks, Rudolf, additional, O'Mara, Tracy A., additional, Aglago, Elom K., additional, Ardanaz, Eva, additional, Bergmann, Manuela M., additional, Bondonno, Nicola P., additional, Braaten, Tonje, additional, Colorado-Yohar, Sandra M., additional, Crous-Bou, Marta, additional, Dahm, Christina C., additional, Fortner, Renée T., additional, Gram, Inger T., additional, Harlid, Sophia, additional, Heath, Alicia K., additional, Idahl, Annika, additional, Kvaskoff, Marina, additional, Nøst, Therese H., additional, Overvad, Kim, additional, Palli, Domenico, additional, Perez-Cornago, Aurora, additional, Sacerdote, Carlotta, additional, Sánchez, Maria-Jose, additional, Schulze, Matthias B., additional, Severi, Gianluca, additional, Simeon, Vittorio, additional, Tagliabue, Giovanna, additional, Tjønneland, Anne, additional, Truong, Thérèse, additional, Tumino, Rosario, additional, Johansson, Mattias, additional, Weiderpass, Elisabete, additional, Murphy, Neil, additional, Gunter, Marc J., additional, Lacey, Ben, additional, Allen, Naomi E., additional, and Dossus, Laure, additional

Published
2022
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