المؤلفون: Andrew R. Hamel, Wenjun Yan, John M. Rouhana, Aboozar Monovarfeshani, Xinyi Jiang, Puja A. Mehta, Jayshree Advani, Yuyang Luo, Qingnan Liang, Skanda Rajasundaram, Arushi Shrivastava, Katherine Duchinski, Sreekar Mantena, Jiali Wang, Tavé van Zyl, Louis R. Pasquale, Anand Swaroop, Puya Gharahkhani, Anthony P. Khawaja, Stuart MacGregor, International Glaucoma Genetics Consortium (IGGC), Rui Chen, Veronique Vitart, Joshua R. Sanes, Janey L. Wiggs, Ayellet V. Segrè

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-25 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/7f45f11f740249d881e78d06fd091c4eTest

المؤلفون: Jue-Sheng Ong, Mathias Seviiri, Jean Claude Dusingize, Yeda Wu, Xikun Han, Jianxin Shi, Catherine M. Olsen, Rachel E. Neale, John F. Thompson, Robyn P. M. Saw, Kerwin F. Shannon, Graham J. Mann, Nicholas G. Martin, Sarah E. Medland, Scott D. Gordon, Richard A. Scolyer, Georgina V. Long, Mark M. Iles, Maria Teresa Landi, David C. Whiteman, Stuart MacGregor, Matthew H. Law

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-12 (2023)

مصطلحات موضوعية: Science

الوصف: Abstract Male-pattern baldness (MPB) is related to dysregulation of androgens such as testosterone. A previously observed relationship between MPB and skin cancer may be due to greater exposure to ultraviolet radiation or indicate a role for androgenic pathways in the pathogenesis of skin cancers. We dissected this relationship via Mendelian randomization (MR) analyses, using genetic data from recent male-only meta-analyses of cutaneous melanoma (12,232 cases; 20,566 controls) and keratinocyte cancers (KCs) (up to 17,512 cases; >100,000 controls), followed by stratified MR analysis by body-sites. We found strong associations between MPB and the risk of KC, but not with androgens, and multivariable models revealed that this relationship was heavily confounded by MPB single nucleotide polymorphisms involved in pigmentation pathways. Site-stratified MR analyses revealed strong associations between MPB with head and neck squamous cell carcinoma and melanoma, suggesting that sun exposure on the scalp, rather than androgens, is the main driver. Men with less hair covering likely explains, at least in part, the higher incidence of melanoma in men residing in countries with high ambient UV.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/104552cdb9d144b6866af7b840d364e2Test

المؤلفون: Mathias Seviiri, Matthew H. Law, Jue-Sheng Ong, Puya Gharahkhani, Pierre Fontanillas, The 23andMe Research Team, Catherine M. Olsen, David C. Whiteman, Stuart MacGregor

المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-14 (2022)

مصطلحات موضوعية: Science

الوصف: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin cancers and have genetic overlap. Here, the authors use a multi-trait genetic and phenotypic analysis to reveal susceptibility loci for BCC and SCC, and report an optimised polygenic risk score for risk stratification.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/e5e726bee58844e491cc8fdc2767f5c3Test

المؤلفون: Anne Senabouth, Maciej Daniszewski, Grace E. Lidgerwood, Helena H. Liang, Damián Hernández, Mehdi Mirzaei, Stacey N. Keenan, Ran Zhang, Xikun Han, Drew Neavin, Louise Rooney, Maria Isabel G. Lopez Sanchez, Lerna Gulluyan, Joao A. Paulo, Linda Clarke, Lisa S. Kearns, Vikkitharan Gnanasambandapillai, Chia-Ling Chan, Uyen Nguyen, Angela M. Steinmann, Rachael A. McCloy, Nona Farbehi, Vivek K. Gupta, David A. Mackey, Guy Bylsma, Nitin Verma, Stuart MacGregor, Matthew J. Watt, Robyn H. Guymer, Joseph E. Powell, Alex W. Hewitt, Alice Pébay

المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-18 (2022)

مصطلحات موضوعية: Science

الوصف: Age-related macular degeneration (AMD) is a leading cause of vision loss, and there is no approved treatment for AMD with geographic atrophy. Here, the authors used transcriptomic and proteomic analyses of patient induced pluripotent stem cell-derived retinal pigment epithelium to better understand disease mechanisms.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/26ee70153c844e808b5ef6d67e2ac7a9Test

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

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)

مصطلحات موضوعية: Science

الوصف: Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/ea46188f0f2c4f0cae58f959caf971a2Test

المؤلفون: Jue-Sheng Ong, Suzanne C. Dixon-Suen, Xikun Han, Jiyuan An, Esophageal Cancer Consortium, and Me Research Team, Upekha Liyanage, Jean-Cluade Dusingize, Johannes Schumacher, Ines Gockel, Anne Böhmer, Janusz Jankowski, Claire Palles, Tracy O’Mara, Amanda Spurdle, Matthew H. Law, Mark M. Iles, Paul Pharoah, Andrew Berchuck, Wei Zheng, Aaron P. Thrift, Catherine Olsen, Rachel E. Neale, Puya Gharahkhani, Penelope M. Webb, Stuart MacGregor

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021)

مصطلحات موضوعية: Science

الوصف: Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/7744806243e1477e9baddee9305b938eTest

المؤلفون: Yan Dora Zhang, Amber N. Hurson, Haoyu Zhang, Parichoy Pal Choudhury, Douglas F. Easton, Roger L. Milne, Jacques Simard, Per Hall, Kyriaki Michailidou, Joe Dennis, Marjanka K. Schmidt, Jenny Chang-Claude, Puya Gharahkhani, David Whiteman, Peter T. Campbell, Michael Hoffmeister, Mark Jenkins, Ulrike Peters, Li Hsu, Stephen B. Gruber, Graham Casey, Stephanie L. Schmit, Tracy A. O’Mara, Amanda B. Spurdle, Deborah J. Thompson, Ian Tomlinson, Immaculata De Vivo, Maria Teresa Landi, Matthew H. Law, Mark M. Iles, Florence Demenais, Rajiv Kumar, Stuart MacGregor, D. Timothy Bishop, Sarah V. Ward, Melissa L. Bondy, Richard Houlston, John K. Wiencke, Beatrice Melin, Jill Barnholtz-Sloan, Ben Kinnersley, Margaret R. Wrensch, Christopher I. Amos, Rayjean J. Hung, Paul Brennan, James McKay, Neil E. Caporaso, Sonja I. Berndt, Brenda M. Birmann, Nicola J. Camp, Peter Kraft, Nathaniel Rothman, Susan L. Slager, Andrew Berchuck, Paul D. P. Pharoah, Thomas A. Sellers, Simon A. Gayther, Celeste L. Pearce, Ellen L. Goode, Joellen M. Schildkraut, Kirsten B. Moysich, Laufey T. Amundadottir, Eric J. Jacobs, Alison P. Klein, Gloria M. Petersen, Harvey A. Risch, Rachel Z. Stolzenberg-Solomon, Brian M. Wolpin, Donghui Li, Rosalind A. Eeles, Christopher A. Haiman, Zsofia Kote-Jarai, Fredrick R. Schumacher, Ali Amin Al Olama, Mark P. Purdue, Ghislaine Scelo, Marlene D. Dalgaard, Mark H. Greene, Tom Grotmol, Peter A. Kanetsky, Katherine A. McGlynn, Katherine L. Nathanson, Clare Turnbull, Fredrik Wiklund, Breast Cancer Association Consortium (BCAC), Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), Colon Cancer Family Registry (CCFR), Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT), Endometrial Cancer Association Consortium (ECAC), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Melanoma Genetics Consortium (GenoMEL), Glioma International Case-Control Study (GICC), International Lung Cancer Consortium (ILCCO), Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph), Ovarian Cancer Association Consortium (OCAC), Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium (PanC4), Pancreatic Cancer Cohort Consortium (PanScan), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), Renal Cancer GWAS, Testicular Cancer Consortium (TECAC), Stephen J. Chanock, Nilanjan Chatterjee, Montserrat Garcia-Closas

المصدر: Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020)

مصطلحات موضوعية: Science

الوصف: In cancer many gene variants may contribute to disease etiology, but the impact of a given gene variant may have varied effect size. Here, the authors analyse summary statistics of genome-wide association studies from fourteen cancers, and show the utility of polygenic risk scores may vary depending on cancer type.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/043bfd656ef148a0993f50953c04b25fTest

المؤلفون: Jiyuan An, Puya Gharahkhani, Matthew H. Law, Jue-Sheng Ong, Xikun Han, Catherine M. Olsen, Rachel E. Neale, John Lai, Tom L. Vaughan, Ines Gockel, René Thieme, Anne C. Böhmer, Janusz Jankowski, Rebecca C. Fitzgerald, Johannes Schumacher, Claire Palles, BEACON, andMe Research Team, David C. Whiteman, Stuart MacGregor

المصدر: Nature Communications, Vol 10, Iss 1, Pp 1-10 (2019)

مصطلحات موضوعية: Science

الوصف: Gastroesophageal reflux disease (GERD) is a major risk factor for Barret’s esophagus (BE) and esophageal adenocarcinoma (EA). Here, An et al. report 25 genetic loci for GERD, many of which associate with BE and EA or with other traits such as BMI.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/69989b38dc994e248ea97c1493de2f41Test

المؤلفون: David L. Duffy, Gu Zhu, Xin Li, Marianna Sanna, Mark M. Iles, Leonie C. Jacobs, David M. Evans, Seyhan Yazar, Jonathan Beesley, Matthew H. Law, Peter Kraft, Alessia Visconti, John C. Taylor, Fan Liu, Margaret J. Wright, Anjali K. Henders, Lisa Bowdler, Dan Glass, M. Arfan Ikram, André G. Uitterlinden, Pamela A. Madden, Andrew C. Heath, Elliot C. Nelson, Adele C. Green, Stephen Chanock, Jennifer H. Barrett, Matthew A. Brown, Nicholas K. Hayward, Stuart MacGregor, Richard A. Sturm, Alex W. Hewitt, Melanoma GWAS Consortium, Manfred Kayser, David J. Hunter, Julia A. Newton Bishop, Timothy D. Spector, Grant W. Montgomery, David A. Mackey, George Davey Smith, Tamar E. Nijsten, D. Timothy Bishop, Veronique Bataille, Mario Falchi, Jiali Han, Nicholas G. Martin

المصدر: Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018)

مصطلحات موضوعية: Science

الوصف: Melanocytic nevus count is associated with melanoma risk. In this study, a meta-analysis of 11 nevus GWAS studies identifies novel SNPs in KITLG and 9q32, and bivariate analysis with melanoma GWAS meta-analysis reveals that most nevus genes affect melanoma risk, while melanoma risk loci do not alter the nevus count.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/ffdbab560c8441628effd5dbb028717dTest

المؤلفون: Adriana I. Iglesias, Aniket Mishra, Veronique Vitart, Yelena Bykhovskaya, René Höhn, Henriët Springelkamp, Gabriel Cuellar-Partida, Puya Gharahkhani, Jessica N. Cooke Bailey, Colin E. Willoughby, Xiaohui Li, Seyhan Yazar, Abhishek Nag, Anthony P. Khawaja, Ozren Polašek, David Siscovick, Paul Mitchell, Yih Chung Tham, Jonathan L. Haines, Lisa S. Kearns, Caroline Hayward, Yuan Shi, Elisabeth M. van Leeuwen, Kent D. Taylor, Blue Mountains Eye Study—GWAS group, Pieter Bonnemaijer, Jerome I. Rotter, Nicholas G. Martin, Tanja Zeller, Richard A. Mills, Emmanuelle Souzeau, Sandra E. Staffieri, Jost B. Jonas, Irene Schmidtmann, Thibaud Boutin, Jae H. Kang, Sionne E. M. Lucas, Tien Yin Wong, Manfred E. Beutel, James F. Wilson, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2), André G. Uitterlinden, Eranga N. Vithana, Paul J. Foster, Pirro G. Hysi, Alex W. Hewitt, Chiea Chuen Khor, Louis R. Pasquale, Grant W. Montgomery, Caroline C. W. Klaver, Tin Aung, Norbert Pfeiffer, David A. Mackey, Christopher J. Hammond, Ching-Yu Cheng, Jamie E. Craig, Yaron S. Rabinowitz, Janey L. Wiggs, Kathryn P. Burdon, Cornelia M. van Duijn, Stuart MacGregor

المصدر: Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018)

مصطلحات موضوعية: Science

الوصف: Reduced central corneal thickness (CCT) is observed in common eye diseases as well as in rare Mendelian disorders. Here, in a cross-ancestry GWAS, the authors identify 19 novel genetic loci associated with CCT, a subset of which is involved in rare corneal or connective tissue disorders.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/f7334f0a8f8b42b18a3180c2a6650fb9Test