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1,995 results on '"Zhang, Hong-Wei"'

5. $L^2$-spectrum, growth indicator function and critical exponent on locally symmetric spaces

Author

Wolf, Lasse L. and Zhang, Hong-Wei

Subjects
Mathematics - Spectral Theory, 22E40, A7A10, 58J50
Abstract

In this short note we observe, on locally symmetric spaces of higher rank, a connection between the growth indicator function introduced by Quint and the modified critical exponent of the Poincar\'e series equipped with the polyhedral distance. As a consequence, we provide a different characterization of the bottom of the $L^2$-spectrum of the Laplace-Beltrami operator in terms of the growth indicator function. Moreover, we explore the relationship between these three objects and the temperedness., Comment: 9 pages

Published
2023

7. Stein-Weiss inequality on non-compact symmetric spaces

Author

Kumar, Vishvesh, Ruzhansky, Michael, and Zhang, Hong-Wei

Subjects
Mathematics - Analysis of PDEs, 22E30, 43A85, 43A90
Abstract

Let $\Delta$ be the Laplace-Beltrami operator on a non-compact symmetric space of any rank, and denote the bottom of its $L^2$-spectrum as $-|\rho|^{2}$. In this paper, we provide a comprehensive characterization of both the sufficient and necessary conditions ensuring the validity of the Stein-Weiss inequality for the entire family of operators $\lbrace{(-\Delta+b)^{-\frac{\sigma}{2}}}\rbrace_{\sigma\ge0,\,b\ge-|\rho|^{2}}$. As an application, some weighted functional inequalities, such as Heisenberg's uncertainty principle, Gagliardo-Nirenberg's interpolation inequality, Pitt's inequality, etc., become available in this context. In particular, their sets of admissible indices are larger than those in the Euclidean setting., Comment: The "fill opacity" feature in Tikz images was automatically disabled in v1. We enable it in this new version

Published
2023

9. Smoothing properties of dispersive equations on non-compact symmetric spaces

Author

Kumar, Vishvesh, Ruzhansky, Michael, and Zhang, Hong-Wei

Subjects
Mathematics - Analysis of PDEs, 22E30, 35J10, 35P25, 43A85, 43A90
Abstract

We establish the Kato-type smoothing property, i.e., global-in-time smoothing estimates with homogeneous weights, for the Schr\"odinger equation on Riemannian symmetric spaces of non-compact type and general rank. These form a rich class of manifolds with nonpositive sectional curvature and exponential volume growth at infinity, e.g., hyperbolic spaces. We achieve it by proving the Stein-Weiss inequality and the resolvent estimate of the corresponding Fourier multiplier, which are of independent interest. Moreover, we extend the comparison principles to symmetric spaces and deduce different types of smoothing properties for the wave equation, the Klein-Gordon equation, the relativistic and general orders Schr\"odinger equations. In particular, we observe that some smoothing properties, which are known to fail on the Euclidean plane, hold on the hyperbolic plane., Comment: 32 pages, 2 figures

Published
2023

13. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

Author

Wang, Anqi, Shen, Jiayi, Rodriguez, Alex A., Saunders, Edward J., Chen, Fei, Janivara, Rohini, Darst, Burcu F., Sheng, Xin, Xu, Yili, Chou, Alisha J., Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Plym, Anna, Sahimi, Ali, Hoffman, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerêdo, Jéssica, Muir, Kenneth, Ito, Shuji, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy P., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Røder, Andreas, Stroomberg, Hein V., Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith A., Tilly, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordstrom, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie, Cook, Michael B., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Jr., Ian M., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L., Ostrander, Elaine A., Koutros, Stella, Beane Freeman, Laura E., Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Butler, Ebonee N., Mohler, James L., Taylor, Jack A., Kogevinas, Manolis, Dierssen-Sotos, Trinidad, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Pilie, Patrick, Yu, Yao, Bohlender, Ryan J., Gu, Jian, Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Brenner, Hermann, Chen, Xuechen, Holleczek, Bernd, Schöttker, Ben, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine M., Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Abraham, Aswin, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer, Petrovics, Gyorgy, Casey, Graham, Wang, Ying, Tettey, Yao, Lachance, Joseph, Tang, Wei, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Yamoah, Kosj, Govindasami, Koveela, Chokkalingam, Anand P., Keaton, Jacob M., Hellwege, Jacklyn N., Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Shittu, Olayiwola, Amodu, Olukemi, Adebiyi, Akindele O., Aisuodionoe-Shadrach, Oseremen I., Ajibola, Hafees O., Jamda, Mustapha A., Oluwole, Olabode P., Nwegbu, Maxwell, Adusei, Ben, Mante, Sunny, Darkwa-Abrahams, Afua, Diop, Halimatou, Gundell, Susan M., Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Kachuri, Linda, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Preuss, Michael H., Loos, Ruth J. F., Zawistowski, Matthew, Zöllner, Sebastian, Lu, Zeyun, Van Den Eeden, Stephen K., Easton, Douglas F., Ambs, Stefan, Edwards, Todd L., Mägi, Reedik, Rebbeck, Timothy R., Fritsche, Lars, Chanock, Stephen J., Berndt, Sonja I., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Gaziano, J. Michael, Justice, Amy C., Mancuso, Nick, Terao, Chikashi, Eeles, Rosalind A., Kote-Jarai, Zsofia, Madduri, Ravi K., Conti, David V., and Haiman, Christopher A.

Published
2023
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14. Asymptotic behavior of the heat semigroup on certain Riemannian manifolds

Author

Grigor'yan, Alexander, Papageorgiou, Effie, and Zhang, Hong-Wei

Subjects
Mathematics - Differential Geometry, Mathematics - Analysis of PDEs, 58J35, 35B40, 35K05
Abstract

We show that, on a complete, connected and non-compact Riemannian manifold of non-negative Ricci curvature, the solution to the heat equation with $L^{1}$ initial data behaves asymptotically as the mass times the heat kernel. In contrast to the previously known results in negatively curved contexts, the radiality assumption on the initial data is not required. Similar long-time convergence results remain valid on more general manifolds satisfying the Li-Yau two-sided estimate of the heat kernel. Moreover, we provide a counterexample such that this asymptotic phenomenon fails in sup norm on manifolds with two Euclidean ends., Comment: to appear in "From Classical Analysis to Analysis on Fractals - The Robert Strichartz Memorial Volume", Springer

Published
2022

16. Asymptotic behavior of solutions to the heat equation on noncompact symmetric spaces

Author

Anker, Jean-Philippe, Papageorgiou, Effie, and Zhang, Hong-Wei

Subjects
Mathematics - Analysis of PDEs, 22E30, 35B40, 35K05, 58J35
Abstract

This paper is twofold. The first part aims to study the long-time asymptotic behavior of solutions to the heat equation on Riemannian symmetric spaces $G/K$ of noncompact type and of general rank. We show that any solution to the heat equation with bi-$K$-invariant $L^{1}$ initial data behaves asymptotically as the mass times the fundamental solution, and provide a counterexample in the non bi-$K$-invariant case. These answer problems recently raised by J.L. V\'azquez. In the second part, we investigate the long-time asymptotic behavior of solutions to the heat equation associated with the so-called distinguished Laplacian on $G/K$. Interestingly, we observe in this case phenomena which are similar to the Euclidean setting, namely $L^1$ asymptotic convergence with no bi-$K$-invariance condition and strong $L^{\infty}$ convergence., Comment: To appear in J. Funct. Anal

Published
2021
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21. Schr\'odinger equation on noncompact symmetric spaces

Author

Anker, Jean-Philippe, Meda, Stefano, Pierfelice, Vittoria, Vallarino, Maria, and Zhang, Hong-Wei

Subjects
Mathematics - Analysis of PDEs, 22E30, 35J10, 35P25, 43A85, 43A90
Abstract

We establish sharp-in-time kernel and dispersive estimates for the Schr\"odinger equation on non-compact Riemannian symmetric spaces of any rank. Due to the particular geometry at infinity and the Kunze-Stein phenomenon, these properties are more pronounced in large time and enable us to prove the global-in-time Strichartz inequality for a larger family of admissible couples than in the Euclidean case. Consequently, we obtain the global well-posedness for the corresponding semilinear equation with lower regularity data and some scattering properties for small powers which are known to fail in the Euclidean setting. The crucial kernel estimates are achieved by combining the stationary phase method based on a subtle barycentric decomposition, a subordination formula of the Schr\"odinger group to the wave propagator and an improved Hadamard parametrix., Comment: 19 pages, major revision with more details

Published
2021
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22. Asymptotic Behavior of the Heat Semigroup on Certain Riemannian Manifolds

Author

Grigor’yan, Alexander, Papageorgiou, Effie, Zhang, Hong-Wei, Benedetto, John J., Series Editor, Czaja, Wojciech, Series Editor, Okoudjou, Kasso, Series Editor, Aldroubi, Akram, Editorial Board Member, Casazza, Peter, Editorial Board Member, Cochran, Douglas, Editorial Board Member, Feichtinger, Hans G., Editorial Board Member, Gilbert, Anna C., Editorial Board Member, Heil, Christopher, Editorial Board Member, Jaffard, Stéphane, Editorial Board Member, Kutyniok, Gitta, Editorial Board Member, Maggioni, Mauro, Editorial Board Member, Molter, Ursula, Editorial Board Member, Shen, Zuowei, Editorial Board Member, Strohmer, Thomas, Editorial Board Member, Unser, Michael, Editorial Board Member, Wang, Yang, Editorial Board Member, Alonso Ruiz, Patricia, editor, Hinz, Michael, editor, Okoudjou, Kasso A., editor, Rogers, Luke G., editor, and Teplyaev, Alexander, editor

Published
2023
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24. Wave equation on general noncompact symmetric spaces

Author

Anker, Jean-Philippe and Zhang, Hong-Wei

Subjects
Mathematics - Analysis of PDEs, 22E30, 35L05, 43A85, 43A90
Abstract

We establish sharp pointwise kernel estimates and dispersive properties for the wave equation on noncompact symmetric spaces of general rank. This is achieved by combining the stationary phase method and the Hadamard parametrix, and in particular, by introducing a subtle spectral decomposition, which allows us to overcome a well-known difficulty in higher rank analysis, namely the fact that the Plancherel density is not a differential symbol in general. As consequences, we deduce the Strichartz inequality for a large family of admissible pairs and prove global well-posedness results for the corresponding semilinear equation with low regularity data as on hyperbolic spaces.

Published
2020

25. Wave equation on certain noncompact symmetric spaces

Author

Zhang, Hong-Wei

Subjects
Mathematics - Analysis of PDEs, 35Q55, 43A85, 22E30, 35P25, 47J35, 58D25
Abstract

In this paper, we prove sharp pointwise kernel estimates and dispersive properties for the linear wave equation on noncompact Riemannian symmetric spaces G/K of any rank with G complex. As a consequence, we deduce Strichartz inequalities for a large family of admissible pairs and prove global well-posedness results for the corresponding semilinear equation with low regularity data as on hyperbolic spaces., Comment: To appear in Pure and Applied Analysis

Published
2020
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26. Bottom of the $L^2$ spectrum of the Laplacian on locally symmetric spaces

Author

Anker, Jean-Philippe and Zhang, Hong-Wei

Subjects
Mathematics - Spectral Theory, Mathematics - Analysis of PDEs
Abstract

We estimate the bottom of the $L^2$ spectrum of the Laplacian on locally symmetric spaces in terms of the critical exponents of appropriate Poincar\'e series. Our main result is the higher rank analog of a characterization due to Elstrodt, Patterson, Sullivan and Corlette in rank one. It improves upon previous results obtained by Leuzinger and Weber in higher rank., Comment: To appear in Geometriae Dedicata

Published
2020
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28. Rapid determination of sulfites by microextraction-ion chromatography in red wine

Author

WANG Zhi-hong, LU Fei, NI Yong-fu, CAO Peng, and ZHANG Hong-wei

Subjects
micro extraction, ion chromatography, red wine, sulfites, Food processing and manufacture, TP368-456
Abstract

Objective: In view of the improvement of the national standard method of distillation pretreatment, combined with the advantages of ion chromatography, a rapid determination of sulfite by microextract-ion chromatography in red wine was established. Methods: Sulfur dioxide was released by microextraction device, which was absorbed by sodium hydroxide solution to form sulfite, and then oxidized to sulfate. The samples were then filtered by 0.45 μm filter and determined by ion chromatograph. Results: The concentration of sulfite ion in range of 1.0~50 mg/L showed a linear relationship with the peak area, with correlation coefficient of 0.999 9, and the detection limit was 0.24 mg/L. The average recoveries of different levels of sulfate were 95.2%~99.1%, and the relative standard deviations (RSD) were 6.84%~8.65%. Conclusion: The method has the advantages of simple and fast pretreatment operation, reduced impurity interference significantly, and is suitable for the detection of batch samples.

Published
2023
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38. Wave and Klein-Gordon equations on certain locally symmetric spaces

Author

Zhang, Hong-Wei

Subjects
Mathematics - Analysis of PDEs
Abstract

This paper is devoted to study the dispersive properties of the linear Klein-Gordon and wave equations on a class of locally symmetric spaces. As a consequence, we obtain the Strichartz estimate and prove global well-posedness results for the corresponding semilinear equation with low regularity data as on real hyperbolic spaces.

Published
2018
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47. Active Heme Metabolism Suppresses Macrophage Phagocytosis via the TLR4/Type I IFN Signaling/CD36 in Uterine Endometrial Cancer.

Author

Zhang, Xing, Yang, Yi‐Xing, Lu, Jia‐Jing, Hou, Ding‐Yu, Abudukeyoumu, Ayitila, Zhang, Hong‐Wei, Li, Ming‐Qing, and Xie, Feng

Subjects
PHAGOCYTIC function tests, METRORRHAGIA, SUCCINATE dehydrogenase, UTERINE cancer, ESTROGEN regulation
Abstract

Background: Uterine endometrial cancer (UEC) is a common gynecological estrogen‐dependent carcinoma, usually accompanied by intermenstrual bleeding. Active heme metabolism frequently plays an increasingly important role in many diseases, especially in cancers. Tumor‐associated macrophages (TAMs) are the major population in the immune microenvironment of UEC. However, the roles of heme metabolisms in the crosstalk between UEC cells (UECCs) and macrophages are unclear. Materials and Methods: In our study, by using TCGA database analysis, integration analysis of the protein–protein interaction (PPI) network and sample RNA transcriptome sequencing were done. The expression level of both heme‐associated molecules and iron metabolism‐related molecules were measured by quantitative real‐time polymerase chain reaction. Heme level detection was done through dehydrohorseradish peroxidase assay. In addition to immunohistochemistry, phagocytosis assay of macrophages, immunofluorescence staining, intracellular ferrous iron staining, as well as enzyme‐linked immune sorbent assay were performed. Results: In the study, we verified that heme accumulation in UECCs is apparently higher than in endometrial epithelium cells. Low expression of succinate dehydrogenase B under the regulation of estrogen contributes to over‐production of succinate and heme accumulation in UECC. More importantly, excessive heme in UECCs impaired macrophage phagocytosis by regulation of CD36. Mechanistically, this process is dependent on toll‐like receptor (TLR4)/type I interferons alpha (IFN Iα) regulatory axis in macrophage. Conclusion: Collectively, these findings elucidate that active heme metabolism of UECCs directly decreases phagocytosis by controlling the secretion of TLR4‐mediated IFN Iα and the expression of CD36, and further contributing to the immune escape of UEC. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Author

Schumacher, Fredrick R, Al Olama, Ali Amin, Berndt, Sonja I, Benlloch, Sara, Ahmed, Mahbubl, Saunders, Edward J, Dadaev, Tokhir, Leongamornlert, Daniel, Anokian, Ezequiel, Cieza-Borrella, Clara, Goh, Chee, Brook, Mark N, Sheng, Xin, Fachal, Laura, Dennis, Joe, Tyrer, Jonathan, Muir, Kenneth, Lophatananon, Artitaya, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Håkansson, Niclas, West, Catharine ML, Dunning, Alison M, Burnet, Neil, Mucci, Lorelei A, Giovannucci, Edward, Andriole, Gerald L, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Beane Freeman, Laura E, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Travis, Ruth C, Key, Tim J, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C, Rosenstein, Barry S, Kerns, Sarah L, Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, FitzGerald, Liesel M, Kibel, Adam S, Drake, Bettina F, Vega, Ana, Gómez-Caamaño, Antonio, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L, Stampfer, Meir, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Stanford, Janet L, and Cybulski, Cezary

Subjects
Cancer, Aging, Prostate Cancer, Genetics, Urologic Diseases, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Case-Control Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk, Profile Study, Australian Prostate Cancer BioResource, IMPACT Study, Canary PASS Investigators, Breast and Prostate Cancer Cohort Consortium, PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Cancer of the Prostate in Sweden, Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci, Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.

Published
2018

49. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Author

Dadaev, Tokhir, Saunders, Edward J, Newcombe, Paul J, Anokian, Ezequiel, Leongamornlert, Daniel A, Brook, Mark N, Cieza-Borrella, Clara, Mijuskovic, Martina, Wakerell, Sarah, Olama, Ali Amin Al, Schumacher, Fredrick R, Berndt, Sonja I, Benlloch, Sara, Ahmed, Mahbubl, Goh, Chee, Sheng, Xin, Zhang, Zhuo, Muir, Kenneth, Govindasami, Koveela, Lophatananon, Artitaya, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Tangen, Catherine M, Goodman, Phyllis, Thompson, Ian M, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail, Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Hakansson, Niclas, West, Catharine, Dunning, Alison M, Burnet, Neil, Mucci, Lorelei, Giovannucci, Edward, Andriole, Gerald, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Freeman, Laura E Beane, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Travis, Ruth C, Key, Tim J, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C, Rosenstein, Barry, Kerns, Sarah, Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, FitzGerald, Liesel M, Kibel, Adam S, Drake, Bettina F, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L, Stampfer, Meir, Park, Jong Y, and Sellers, Thomas A

Subjects
Genetics, Aging, Urologic Diseases, Prostate Cancer, Prevention, Human Genome, Cancer, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Algorithms, Bayes Theorem, Black People, Chromosome Mapping, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Molecular Sequence Annotation, Multivariate Analysis, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Quantitative Trait Loci, Risk, White People, PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium
Abstract

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

Published
2018

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