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Meta-Analysis
. 2013 Jan 15;22(2):408-15.
doi: 10.1093/hmg/dds425. Epub 2012 Oct 12.

A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

Ali Amin Al Olama  1 , Zsofia Kote-Jarai, Fredrick R Schumacher, Fredrik Wiklund, Sonja I Berndt, Sara Benlloch, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, David J Hunter, Brian E Henderson, Michael J Thun, Michael Gaziano, Edward L Giovannucci, Afshan Siddiq, Ruth C Travis, David G Cox, Federico Canzian, Elio Riboli, Timothy J Key, Gerald Andriole, Demetrius Albanes, Richard B Hayes, Johanna Schleutker, Anssi Auvinen, Teuvo L J Tammela, Maren Weischer, Janet L Stanford, Elaine A Ostrander, Cezary Cybulski, Jan Lubinski, Stephen N Thibodeau, Daniel J Schaid, Karina D Sorensen, Jyotsna Batra, Judith A Clements, Suzanne Chambers, Joanne Aitken, Robert A Gardiner, Christiane Maier, Walther Vogel, Thilo Dörk, Hermann Brenner, Tomonori Habuchi, Sue Ingles, Esther M John, Joanne L Dickinson, Lisa Cannon-Albright, Manuel R Teixeira, Radka Kaneva, Hong-Wei Zhang, Yong-Jie Lu, Jong Y Park, Kathleen A Cooney, Kenneth R Muir, Daniel A Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Nadiya Mahmud, Michelle Guy, Koveela Govindasami, Lynne T O'Brien, Rosemary A Wilkinson, Amanda L Hall, Emma J Sawyer, Tokhir Dadaev, Jonathan Morrison, David P Dearnaley, Alan Horwich, Robert A Huddart, Vincent S Khoo, Christopher C Parker, Nicholas Van As, Christopher J Woodhouse, Alan Thompson, Tim Dudderidge, Chris Ogden, Colin S Cooper, Artitaya Lophatonanon, Melissa C Southey, John L Hopper, Dallas English, Jarmo Virtamo, Loic Le Marchand, Daniele Campa, Rudolf Kaaks, Sara Lindstrom, W Ryan Diver, Susan Gapstur, Meredith Yeager, Angela Cox, Mariana C Stern, Roman Corral, Markus Aly, William Isaacs, Jan Adolfsson, Jianfeng Xu, S Lilly Zheng, Tiina Wahlfors, Kimmo Taari, Paula Kujala, Peter Klarskov, Børge G Nordestgaard, M Andreas Røder, Ruth Frikke-Schmidt, Stig E Bojesen, Liesel M FitzGerald, Suzanne Kolb, Erika M Kwon, Danielle M Karyadi, Torben Falck Orntoft, Michael Borre, Antje Rinckleb, Manuel Luedeke, Kathleen Herkommer, Andreas Meyer, Jürgen Serth, James R Marthick, Briony Patterson, Dominika Wokolorczyk, Amanda Spurdle, Felicity Lose, Shannon K McDonnell, Amit D Joshi, Ahva Shahabi, Pedro Pinto, Joana Santos, Ana Ray, Thomas A Sellers, Hui-Yi Lin, Robert A Stephenson, Craig Teerlink, Heiko Muller, Dietrich Rothenbacher, Norihiko Tsuchiya, Shintaro Narita, Guang-Wen Cao, Chavdar Slavov, Vanio Mitev; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology; UK ProtecT Study Collaborators; Australian Prostate Cancer Bioresource; PRACTICAL Consortium; Stephen Chanock, Henrik Gronberg, Christopher A Haiman, Peter Kraft, Douglas F Easton, Rosalind A Eeles
Affiliations
Meta-Analysis

A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

Ali Amin Al Olama et al. Hum Mol Genet. .

Abstract

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

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Figures

Figure 1.
Figure 1.
Regional plots of the associated SNPs at (A) 19q13 and (B) 22q13. Circles and diamonds denote imputed and genotyped SNPs, respectively. Plots show the genomic regions associated with PrCa and –log10 association P-values of SNPs. Also shown are the SNP build 36/hg18 coordinates in kilo bases, recombination rates and genes in the region. The intensity of red shading indicates the strength of LD (r2) with the index SNP. Plots were drawn with a modified R script from http://www.broadinstitute.org/mpg/snap/ldplot.php.
See this image and copyright information in PMC

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