| Title |
Genome-wide association and pathway analysis of left ventricular function after anthracycline exposure in adults
|
|---|---|
| Published in |
Pharmacogenetics and Genomics, July 2017
|
| DOI | 10.1097/fpc.0000000000000284 |
| Pubmed ID | |
| Authors |
Quinn S. Wells, Olivia J. Veatch, Joshua P. Fessel, Aron Y. Joon, Rebecca T. Levinson, Jonathan D. Mosley, Elizabeth P. Held, Chase S. Lindsay, Christian M. Shaffer, Peter E. Weeke, Andrew M. Glazer, Kevin R. Bersell, Sara L. Van Driest, Jason H. Karnes, Marcia A. Blair, Lore W. Lagrone, Yan R. Su, Erica A. Bowton, Ziding Feng, Bonnie Ky, Daniel J. Lenihan, Michael J. Fisch, Joshua C. Denny, Dan M. Roden |
| Abstract |
Anthracyclines are important chemotherapeutic agents, but their use is limited by cardiotoxicity. Candidate gene and genome-wide studies have identified putative risk loci for overt cardiotoxicity and heart failure, but there has been no comprehensive assessment of genomic variation influencing the intermediate phenotype of anthracycline-related changes in left ventricular (LV) function. The purpose of this study was to identify genetic factors influencing changes in LV function after anthracycline chemotherapy. We conducted a genome-wide association study (GWAS) of change in LV function after anthracycline exposure in 385 patients identified from BioVU, a resource linking DNA samples to de-identified electronic medical record data. Variants with P values less than 1×10 were independently tested for replication in a cohort of 181 anthracycline-exposed patients from a prospective clinical trial. Pathway analysis was performed to assess combined effects of multiple genetic variants. Both cohorts were middle-aged adults of predominantly European descent. Among 11 candidate loci identified in discovery GWAS, one single nucleotide polymorphism near PR domain containing 2, with ZNF domain (PRDM2), rs7542939, had a combined P value of 6.5×10 in meta-analysis. Eighteen Kyoto Encyclopedia of Gene and Genomes pathways showed strong enrichment for variants associated with the primary outcome. Identified pathways related to DNA repair, cellular metabolism, and cardiac remodeling. Using genome-wide association we identified a novel candidate susceptibility locus near PRDM2. Variation in genes belonging to pathways related to DNA repair, metabolism, and cardiac remodeling may influence changes in LV function after anthracycline exposure. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 43% |
| Unknown | 4 | 57% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 43% |
| Scientists | 2 | 29% |
| Practitioners (doctors, other healthcare professionals) | 2 | 29% |
Mendeley readers
The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 2% |
| Unknown | 60 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 16% |
| Student > Bachelor | 9 | 15% |
| Researcher | 9 | 15% |
| Student > Doctoral Student | 5 | 8% |
| Student > Master | 4 | 7% |
| Other | 10 | 16% |
| Unknown | 14 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 19 | 31% |
| Biochemistry, Genetics and Molecular Biology | 12 | 20% |
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 10% |
| Nursing and Health Professions | 3 | 5% |
| Agricultural and Biological Sciences | 3 | 5% |
| Other | 3 | 5% |
| Unknown | 15 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 11 June 2017.
All research outputs
#7,303,959
of 25,382,440 outputs
Outputs from Pharmacogenetics and Genomics
#294
of 1,236 outputs
Outputs of similar age
#108,438
of 326,855 outputs
Outputs of similar age from Pharmacogenetics and Genomics
#5
of 13 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 1,236 research outputs from this source. They receive a mean Attention Score of 3.8. This one has done well, scoring higher than 76% of its peers.
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We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.