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Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Overview of attention for article published in Human Molecular Genetics, May 2015
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Title
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Published in
Human Molecular Genetics, May 2015
DOI 10.1093/hmg/ddv203
Pubmed ID
Authors

Ali Amin Al Olama, Tokhir Dadaev, Dennis J. Hazelett, Qiuyan Li, Daniel Leongamornlert, Edward J. Saunders, Sarah Stephens, Clara Cieza-Borrella, Ian Whitmore, Sara Benlloch Garcia, Graham G. Giles, Melissa C. Southey, Liesel Fitzgerald, Henrik Gronberg, Fredrik Wiklund, Markus Aly, Brian E. Henderson, Fredrick Schumacher, Christopher A. Haiman, Johanna Schleutker, Tiina Wahlfors, Teuvo L. Tammela, Børge G. Nordestgaard, Tim J. Key, Ruth C. Travis, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Paul Pharoah, Nora Pashayan, Kay-Tee Khaw, Janet L. Stanford, Stephen N. Thibodeau, Shannon K. Mcdonnell, Daniel J. Schaid, Christiane Maier, Walther Vogel, Manuel Luedeke, Kathleen Herkommer, Adam S. Kibel, Cezary Cybulski, Dominika Wokołorczyk, Wojciech Kluzniak, Lisa Cannon-Albright, Hermann Brenner, Katja Butterbach, Volker Arndt, Jong Y. Park, Thomas Sellers, Hui-Yi Lin, Chavdar Slavov, Radka Kaneva, Vanio Mitev, Jyotsna Batra, Judith A. Clements, Amanda Spurdle, Manuel R. Teixeira, Paula Paulo, Sofia Maia, Hardev Pandha, Agnieszka Michael, Andrzej Kierzek, Koveela Govindasami, Michelle Guy, Artitaya Lophatonanon, Kenneth Muir, Ana Viñuela, Andrew A. Brown, Mathew Freedman, David V. Conti, Douglas Easton, Gerhard A. Coetzee, Rosalind A. Eeles, Zsofia Kote-Jarai, Douglas F. Easton, Paul Pharoah, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Andrew Berchuck, Rosalind A. Eeles, Douglas F. Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Georgia Chenevix-Trench, Antonis Antoniou, Lesley McGuffog, Fergus Couch, Ken Offit, Joe Dennis, Alison M. Dunning, Andrew Lee, Ed Dicks, Craig Luccarini, Javier Benitez, Anna Gonzalez-Neira, Jacques Simard, Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissière, Frederic Robidoux, Stig E. Bojesen, Sune F. Nielsen, Borge G. Nordestgaard, Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer

Abstract

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large scale genotyping and imputation in 25,723 PrCa cases and 26,274 controls of European ancestry.We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, whilst the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed 2 association signals in Europeans that had been previously reported only in East-Asian GWAS.Based on statistical evidence and LD structure we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain approximately 38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.

X Demographics

X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 185 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 3 2%
United States 2 1%
Unknown 180 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 24 13%
Researcher 19 10%
Student > Master 16 9%
Professor 15 8%
Student > Doctoral Student 14 8%
Other 41 22%
Unknown 56 30%
Readers by discipline Count As %
Medicine and Dentistry 51 28%
Biochemistry, Genetics and Molecular Biology 24 13%
Agricultural and Biological Sciences 22 12%
Computer Science 7 4%
Business, Management and Accounting 3 2%
Other 16 9%
Unknown 62 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 September 2015.
All research outputs
#14,026,250
of 24,792,414 outputs
Outputs from Human Molecular Genetics
#6,113
of 8,246 outputs
Outputs of similar age
#122,074
of 271,069 outputs
Outputs of similar age from Human Molecular Genetics
#63
of 123 outputs
Altmetric has tracked 24,792,414 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,246 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 271,069 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
We're also able to compare this research output to 123 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.