A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose
- Publication Date
- March 20, 2009
- Journal
- PLOS Genetics
- Authors
- Fumihiko Takeuchi, Ralph Mc Ginnis, Stephane Bourgeois, Chris Barnes, et al
- Volume
- 5
- Issue
- 3
- Pages
- e1000433
- DOI
- https://dx.plos.org/10.1371/journal.pgen.1000433
- Publisher URL
- http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1000433
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/19300499
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652833
- Europe PMC
- http://europepmc.org/abstract/MED/19300499
- Web of Science
- 000266320100039
- Scopus
- 63449117825
- Mendeley
- http://www.mendeley.com/research/genomewide-association-study-confirms-vkorc1-cyp2c9-cyp4f2-principal-genetic-determinants-warfarin-d
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CiteULike | Further Information
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Mendeley | Further Information
{"title"=>"A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose", "type"=>"journal", "authors"=>[{"first_name"=>"Fumihiko", "last_name"=>"Takeuchi", "scopus_author_id"=>"7103237031"}, {"first_name"=>"Ralph", "last_name"=>"McGinnis", "scopus_author_id"=>"7003755585"}, {"first_name"=>"Stephane", "last_name"=>"Bourgeois", "scopus_author_id"=>"8098017100"}, {"first_name"=>"Chris", "last_name"=>"Barnes", "scopus_author_id"=>"24764733700"}, {"first_name"=>"Niclas", "last_name"=>"Eriksson", "scopus_author_id"=>"15072587100"}, {"first_name"=>"Nicole", "last_name"=>"Soranzo", "scopus_author_id"=>"55800239500"}, {"first_name"=>"Pamela", "last_name"=>"Whittaker", "scopus_author_id"=>"56804575900"}, {"first_name"=>"Venkatesh", "last_name"=>"Ranganath", "scopus_author_id"=>"21741481400"}, {"first_name"=>"Vasudev", "last_name"=>"Kumanduri", "scopus_author_id"=>"12776775800"}, {"first_name"=>"William", "last_name"=>"McLaren", "scopus_author_id"=>"16686734100"}, {"first_name"=>"Lennart", "last_name"=>"Holm", "scopus_author_id"=>"24080378700"}, {"first_name"=>"Jonatan", "last_name"=>"Lindh", "scopus_author_id"=>"7003857375"}, {"first_name"=>"Anders", "last_name"=>"Rane", "scopus_author_id"=>"7102519032"}, {"first_name"=>"Mia", "last_name"=>"Wadelius", "scopus_author_id"=>"6603005522"}, {"first_name"=>"Panos", "last_name"=>"Deloukas", "scopus_author_id"=>"7003287098"}], "year"=>2009, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-63449117825", "pui"=>"354404871", "pmid"=>"19300499", "issn"=>"15537390", "isbn"=>"1553-7404 (Electronic)", "doi"=>"10.1371/journal.pgen.1000433", "sgr"=>"63449117825"}, "id"=>"eb6ae9b8-f78e-3512-92af-86e327b8feb6", "abstract"=>"We report the first genome-wide association study (GWAS) whose sample size (1,053 Swedish subjects) is sufficiently powered to detect genome-wide significance (p<1.5 x 10(-7)) for polymorphisms that modestly alter therapeutic warfarin dose. The anticoagulant drug warfarin is widely prescribed for reducing the risk of stroke, thrombosis, pulmonary embolism, and coronary malfunction. However, Caucasians vary widely (20-fold) in the dose needed for therapeutic anticoagulation, and hence prescribed doses may be too low (risking serious illness) or too high (risking severe bleeding). Prior work established that approximately 30% of the dose variance is explained by single nucleotide polymorphisms (SNPs) in the warfarin drug target VKORC1 and another approximately 12% by two non-synonymous SNPs (*2, *3) in the cytochrome P450 warfarin-metabolizing gene CYP2C9. We initially tested each of 325,997 GWAS SNPs for association with warfarin dose by univariate regression and found the strongest statistical signals (p<10(-78)) at SNPs clustering near VKORC1 and the second lowest p-values (p<10(-31)) emanating from CYP2C9. No other SNPs approached genome-wide significance. To enhance detection of weaker effects, we conducted multiple regression adjusting for known influences on warfarin dose (VKORC1, CYP2C9, age, gender) and identified a single SNP (rs2108622) with genome-wide significance (p = 8.3 x 10(-10)) that alters protein coding of the CYP4F2 gene. We confirmed this result in 588 additional Swedish patients (p<0.0029) and, during our investigation, a second group provided independent confirmation from a scan of warfarin-metabolizing genes. We also thoroughly investigated copy number variations, haplotypes, and imputed SNPs, but found no additional highly significant warfarin associations. We present power analysis of our GWAS that is generalizable to other studies, and conclude we had 80% power to detect genome-wide significance for common causative variants or markers explaining at least 1.5% of dose variance. These GWAS results provide further impetus for conducting large-scale trials assessing patient benefit from genotype-based forecasting of warfarin dose.", "link"=>"http://www.mendeley.com/research/genomewide-association-study-confirms-vkorc1-cyp2c9-cyp4f2-principal-genetic-determinants-warfarin-d", "reader_count"=>231, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>17, "Librarian"=>1, "Researcher"=>49, "Student > Doctoral Student"=>12, "Student > Ph. D. Student"=>42, "Student > Postgraduate"=>18, "Student > Master"=>30, "Other"=>7, "Student > Bachelor"=>39, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>5, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>17, "Librarian"=>1, "Researcher"=>49, "Student > Doctoral Student"=>12, "Student > Ph. D. Student"=>42, "Student > Postgraduate"=>18, "Student > Master"=>30, "Other"=>7, "Student > Bachelor"=>39, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>5, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>11, "Agricultural and Biological Sciences"=>111, "Business, Management and Accounting"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Chemical Engineering"=>1, "Computer Science"=>4, "Decision Sciences"=>1, "Earth and Planetary Sciences"=>1, "Engineering"=>1, "Environmental Science"=>3, "Biochemistry, Genetics and Molecular Biology"=>20, "Mathematics"=>2, "Medicine and Dentistry"=>61, "Design"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>7, "Psychology"=>3, "Social Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>61}, "Social Sciences"=>{"Social Sciences"=>2}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Psychology"=>{"Psychology"=>3}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>11}, "Environmental Science"=>{"Environmental Science"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>7}, "Chemical Engineering"=>{"Chemical Engineering"=>1}, "Design"=>{"Design"=>1}, "Engineering"=>{"Engineering"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>111}, "Computer Science"=>{"Computer Science"=>4}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>20}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "Colombia"=>1, "United States"=>6, "Japan"=>3, "United Kingdom"=>1, "Portugal"=>2, "Switzerland"=>1, "Russia"=>1, "Spain"=>2, "Canada"=>1, "Netherlands"=>1, "Pakistan"=>1, "Brazil"=>1, "Mexico"=>3, "Italy"=>1, "France"=>1, "Chile"=>1, "Germany"=>2}, "group_count"=>14}CrossRef
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- {"month"=>"2", "year"=>"2015", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"72"}
- {"month"=>"3", "year"=>"2015", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"118"}
- {"month"=>"4", "year"=>"2015", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"115"}
- {"month"=>"5", "year"=>"2015", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"115"}
- {"month"=>"6", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"64"}
- {"month"=>"7", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"47"}
- {"month"=>"8", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"62"}
- {"month"=>"9", "year"=>"2015", "pdf_views"=>"18", "xml_views"=>"1", "html_views"=>"106"}
- {"month"=>"10", "year"=>"2015", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"109"}
- {"month"=>"11", "year"=>"2015", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"99"}
- {"month"=>"12", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"102"}
- {"month"=>"1", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"87"}
- {"month"=>"2", "year"=>"2016", "pdf_views"=>"29", "xml_views"=>"1", "html_views"=>"79"}
- {"month"=>"3", "year"=>"2016", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"75"}
- {"month"=>"4", "year"=>"2016", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"148"}
- {"month"=>"5", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"67"}
- {"month"=>"6", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"50"}
- {"month"=>"7", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"53"}
- {"month"=>"8", "year"=>"2016", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"78"}
- {"month"=>"9", "year"=>"2016", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"116"}
- {"month"=>"10", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"84"}
- {"month"=>"11", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"102"}
- {"month"=>"12", "year"=>"2016", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"83"}
- {"month"=>"1", "year"=>"2017", "pdf_views"=>"23", "xml_views"=>"3", "html_views"=>"69"}
- {"month"=>"2", "year"=>"2017", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"84"}
- {"month"=>"3", "year"=>"2017", "pdf_views"=>"17", "xml_views"=>"3", "html_views"=>"81"}
- {"month"=>"4", "year"=>"2017", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"87"}
- {"month"=>"5", "year"=>"2017", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"84"}
- {"month"=>"6", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"53"}
- {"month"=>"7", "year"=>"2017", "pdf_views"=>"29", "xml_views"=>"1", "html_views"=>"109"}
- {"month"=>"8", "year"=>"2017", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"53"}
- {"month"=>"9", "year"=>"2017", "pdf_views"=>"21", "xml_views"=>"2", "html_views"=>"55"}
- {"month"=>"10", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"3", "html_views"=>"46"}
- {"month"=>"11", "year"=>"2017", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"91"}
- {"month"=>"12", "year"=>"2017", "pdf_views"=>"27", "xml_views"=>"1", "html_views"=>"109"}
- {"month"=>"1", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"68"}
- {"month"=>"2", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"22"}
- {"month"=>"3", "year"=>"2018", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"39"}
- {"month"=>"4", "year"=>"2018", "pdf_views"=>"45", "xml_views"=>"1", "html_views"=>"73"}
- {"month"=>"5", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"50"}
- {"month"=>"6", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"40"}
- {"month"=>"7", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"5", "html_views"=>"23"}
- {"month"=>"8", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"30"}
- {"month"=>"9", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"22"}
- {"month"=>"10", "year"=>"2018", "pdf_views"=>"24", "xml_views"=>"1", "html_views"=>"62"}
- {"month"=>"11", "year"=>"2018", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"47"}
- {"month"=>"12", "year"=>"2018", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"52"}
- {"month"=>"1", "year"=>"2019", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"45"}
- {"month"=>"2", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"33"}
- {"month"=>"3", "year"=>"2019", "pdf_views"=>"16", "xml_views"=>"2", "html_views"=>"34"}
- {"month"=>"4", "year"=>"2019", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"55"}
- {"month"=>"5", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"34"}
- {"month"=>"6", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"12"}
- {"month"=>"7", "year"=>"2019", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"30"}
- {"month"=>"8", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"14"}
- {"month"=>"9", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"9"}
- {"month"=>"10", "year"=>"2019", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"28"}
- {"month"=>"11", "year"=>"2019", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"49"}
- {"month"=>"12", "year"=>"2019", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"11"}
PMC Usage Stats | Further Information
- {"month"=>"1", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"102", "year"=>"2010", "pdf"=>"68", "unique-ip"=>"96", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"4"}
- {"scanned-page-browse"=>"0", "month"=>"2", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"74", "unique-ip"=>"70", "pdf"=>"58", "year"=>"2010", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"1"}
- {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"6", "full-text"=>"135", "year"=>"2010", "pdf"=>"84", "unique-ip"=>"117", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"3"}
- {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"90", "unique-ip"=>"78", "pdf"=>"51", "year"=>"2010", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"19"}
- {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"1", "abstract"=>"4", "full-text"=>"92", "year"=>"2010", "pdf"=>"50", "unique-ip"=>"77", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"14"}
- {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"80", "unique-ip"=>"75", "pdf"=>"54", "year"=>"2010", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"12"}
- {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"75", "year"=>"2010", "pdf"=>"52", "unique-ip"=>"74", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"11"}
- {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"50", "unique-ip"=>"48", "pdf"=>"32", "year"=>"2010", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"3"}
- {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"57", "year"=>"2010", "pdf"=>"42", "unique-ip"=>"62", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"4"}
- {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"51", "unique-ip"=>"52", "pdf"=>"39", "year"=>"2010", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"13"}
- {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"62", "year"=>"2010", "pdf"=>"43", "unique-ip"=>"64", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"5"}
- {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"52", "unique-ip"=>"54", "pdf"=>"41", "year"=>"2010", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"10"}
- {"month"=>"1", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"58", "year"=>"2011", "pdf"=>"36", "unique-ip"=>"49", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"6"}
- {"scanned-page-browse"=>"0", "month"=>"2", "cited-by"=>"1", "abstract"=>"1", "full-text"=>"78", "unique-ip"=>"73", "pdf"=>"46", "year"=>"2011", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
- {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"73", "year"=>"2011", "pdf"=>"47", "unique-ip"=>"74", "figure"=>"20", "scanned-summary"=>"0", "supp-data"=>"6"}
- {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"1", "abstract"=>"0", "full-text"=>"93", "unique-ip"=>"78", "pdf"=>"55", "year"=>"2011", "figure"=>"12", "scanned-summary"=>"0", "supp-data"=>"1"}
- {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"51", "year"=>"2011", "pdf"=>"35", "unique-ip"=>"53", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"1"}
- {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"65", "unique-ip"=>"58", "pdf"=>"36", "year"=>"2011", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"4"}
- {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"40", "year"=>"2011", "pdf"=>"23", "unique-ip"=>"40", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"6"}
- {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"40", "unique-ip"=>"40", "pdf"=>"25", "year"=>"2011", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"2"}
- {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"49", "year"=>"2011", "pdf"=>"25", "unique-ip"=>"44", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"1"}
- {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"1", "abstract"=>"0", "full-text"=>"66", "unique-ip"=>"64", "pdf"=>"40", "year"=>"2011", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"1"}
- {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"53", "year"=>"2011", "pdf"=>"22", "unique-ip"=>"48", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
- {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"51", "unique-ip"=>"44", "pdf"=>"29", "year"=>"2011", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"8"}
- {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"51", "unique-ip"=>"49", "pdf"=>"26", "year"=>"2012", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"1"}
- {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"48", "year"=>"2012", "pdf"=>"30", "unique-ip"=>"46", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
- {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"62", "unique-ip"=>"54", "pdf"=>"29", "year"=>"2012", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"12"}
- {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"44", "year"=>"2012", "pdf"=>"28", "unique-ip"=>"47", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"3"}
- {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"71", "unique-ip"=>"60", "pdf"=>"30", "year"=>"2012", "figure"=>"17", "scanned-summary"=>"0", "supp-data"=>"2"}
- {"month"=>"3", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"119", "year"=>"2009", "pdf"=>"95", "unique-ip"=>"110", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"32"}
- {"scanned-page-browse"=>"0", "month"=>"4", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"253", "unique-ip"=>"209", "pdf"=>"184", "year"=>"2009", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"45"}
- {"month"=>"5", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"136", "year"=>"2009", "pdf"=>"108", "unique-ip"=>"119", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"10"}
- {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"156", "unique-ip"=>"148", "pdf"=>"114", "year"=>"2009", "figure"=>"13", "scanned-summary"=>"0", "supp-data"=>"2"}
- {"month"=>"7", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"152", "year"=>"2009", "pdf"=>"122", "unique-ip"=>"137", "figure"=>"12", "scanned-summary"=>"0", "supp-data"=>"17"}
- {"scanned-page-browse"=>"0", "month"=>"8", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"106", "unique-ip"=>"99", "pdf"=>"98", "year"=>"2009", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"13"}
- {"month"=>"9", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"116", "year"=>"2009", "pdf"=>"87", "unique-ip"=>"98", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"21"}
- {"scanned-page-browse"=>"0", "month"=>"10", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"56", "unique-ip"=>"49", "pdf"=>"33", "year"=>"2009", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"10"}
- {"month"=>"11", "scanned-page-browse"=>"0", "cited-by"=>"1", "abstract"=>"3", "full-text"=>"151", "year"=>"2009", "pdf"=>"110", "unique-ip"=>"139", "figure"=>"12", "scanned-summary"=>"0", "supp-data"=>"5"}
- {"scanned-page-browse"=>"0", "month"=>"12", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"96", "unique-ip"=>"83", "pdf"=>"74", "year"=>"2009", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"5"}
- {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"40", "year"=>"2012", "pdf"=>"16", "unique-ip"=>"34", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"4"}
- {"unique-ip"=>"40", "full-text"=>"44", "pdf"=>"20", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
- {"unique-ip"=>"33", "full-text"=>"43", "pdf"=>"20", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
- {"unique-ip"=>"49", "full-text"=>"49", "pdf"=>"32", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
- {"unique-ip"=>"46", "full-text"=>"53", "pdf"=>"18", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"6", "cited-by"=>"2", "year"=>"2012", "month"=>"10"}
- {"unique-ip"=>"28", "full-text"=>"25", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
- {"unique-ip"=>"42", "full-text"=>"45", "pdf"=>"20", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
- {"unique-ip"=>"38", "full-text"=>"48", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
- {"unique-ip"=>"40", "full-text"=>"40", "pdf"=>"15", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
- {"unique-ip"=>"37", "full-text"=>"45", "pdf"=>"16", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
- {"unique-ip"=>"34", "full-text"=>"32", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
- {"unique-ip"=>"28", "full-text"=>"39", "pdf"=>"16", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
- {"unique-ip"=>"20", "full-text"=>"20", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
- {"unique-ip"=>"26", "full-text"=>"27", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
- {"unique-ip"=>"23", "full-text"=>"28", "pdf"=>"10", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
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