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CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer

Overview of attention for article published in Endocrine-Related Cancer, November 2015
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Title
CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer
Published in
Endocrine-Related Cancer, November 2015
DOI 10.1530/erc-15-0386
Pubmed ID
Authors

Deborah J Thompson, Tracy A O'Mara, Dylan M Glubb, Jodie N Painter, Timothy Cheng, Elizabeth Folkerd, Deborah Doody, Joe Dennis, Penelope M Webb, Maggie Gorman, Lynn Martin, Shirley Hodgson, Kyriaki Michailidou, Jonathan P Tyrer, Mel J Maranian, Per Hall, Kamila Czene, Hatef Darabi, Jingmei Li, Peter A Fasching, Alexander Hein, Matthias W Beckmann, Arif B Ekici, Thilo Dörk, Peter Hillemanns, Matthias Dürst, Ingo Runnebaum, Hui Zhao, Jeroen Depreeuw, Stefanie Schrauwen, Frederic Amant, Ellen L Goode, Brooke L Fridley, Sean C Dowdy, Stacey J Winham, Helga B Salvesen, Jone Trovik, Tormund S Njolstad, Henrica M J Werner, Katie Ashton, Tony Proietto, Geoffrey Otton, Luis Carvajal-Carmona, Emma Tham, Tao Liu, Miriam Mints, Rodney J Scott, Mark McEvoy, John Attia, Elizabeth G Holliday, Grant W Montgomery, Nicholas G Martin, Dale R Nyholt, Anjali K Henders, John L Hopper, Nadia Traficante, Matthias Ruebner, Anthony J Swerdlow, Barbara Burwinkel, Hermann Brenner, Alfons Meindl, Hiltrud Brauch, Annika Lindblom, Diether Lambrechts, Jenny Chang-Claude, Fergus J Couch, Graham G Giles, Vessela N Kristensen, Angela Cox, Manjeet K Bolla, Qin Wang, Stig E Bojesen, Mitul Shah, Robert Luben, Kay-Tee Khaw, Paul D P Pharoah, Alison M Dunning, Ian Tomlinson, Mitch Dowsett, Douglas F Easton, Amanda B Spurdle

Abstract

Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol concentrations. We analysed 2,937 SNPs in 6,608 endometrial cancer cases and 37,925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10-11). SNP rs727479 was also among those most strongly associated with circulating estradiol concentrations in 2,767 post-menopausal controls (P=7.4x10-8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on estradiol concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by estradiol. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 76 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 76 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 16%
Student > Ph. D. Student 11 14%
Other 7 9%
Professor 6 8%
Student > Master 6 8%
Other 14 18%
Unknown 20 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 28%
Medicine and Dentistry 16 21%
Agricultural and Biological Sciences 6 8%
Mathematics 2 3%
Nursing and Health Professions 1 1%
Other 5 7%
Unknown 25 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 18 November 2015.
All research outputs
#17,376,384
of 25,498,750 outputs
Outputs from Endocrine-Related Cancer
#1,060
of 1,511 outputs
Outputs of similar age
#164,197
of 274,925 outputs
Outputs of similar age from Endocrine-Related Cancer
#14
of 20 outputs
Altmetric has tracked 25,498,750 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,511 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 22nd percentile – i.e., 22% 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 274,925 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.