Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study
Publication Date
August 25, 2015
Journal
PLOS Medicine
Authors
Lauren E. Mokry, Stephanie Ross, Omar S. Ahmad, Vincenzo Forgetta, et al
Volume
12
Issue
8
Pages
e1001866
DOI
https://dx.plos.org/10.1371/journal.pmed.1001866
Publisher URL
http://journals.plos.org/plosmedicine/article?id=10.1371%2Fjournal.pmed.1001866
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/26305103
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549308
Europe PMC
http://europepmc.org/abstract/MED/26305103
Web of Science
000360708300008
Scopus
84940745586
Mendeley
http://www.mendeley.com/research/vitamin-d-risk-multiple-sclerosis-mendelian-randomization-study-4
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{"title"=>"Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study", "type"=>"journal", "authors"=>[{"first_name"=>"Lauren E.", "last_name"=>"Mokry", "scopus_author_id"=>"56578371700"}, {"first_name"=>"Stephanie", "last_name"=>"Ross", "scopus_author_id"=>"55212899800"}, {"first_name"=>"Omar S.", "last_name"=>"Ahmad", "scopus_author_id"=>"49760889000"}, {"first_name"=>"Vincenzo", "last_name"=>"Forgetta", "scopus_author_id"=>"6503914820"}, {"first_name"=>"George Davey", "last_name"=>"Smith", "scopus_author_id"=>"35354080500"}, {"first_name"=>"Aaron", "last_name"=>"Leong", "scopus_author_id"=>"12794363900"}, {"first_name"=>"Celia M.T.", "last_name"=>"Greenwood", "scopus_author_id"=>"34570534700"}, {"first_name"=>"George", "last_name"=>"Thanassoulis", "scopus_author_id"=>"24829870900"}, {"first_name"=>"J. Brent", "last_name"=>"Richards", "scopus_author_id"=>"56706824400"}], "year"=>2015, "source"=>"PLoS Medicine", "identifiers"=>{"scopus"=>"2-s2.0-84940745586", "sgr"=>"84940745586", "issn"=>"15491676", "doi"=>"10.1371/journal.pmed.1001866", "pmid"=>"26305103", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)", "pui"=>"605889201"}, "id"=>"e5369057-1ccf-3769-975b-37fd3d550847", "abstract"=>"BACKGROUND: Observational studies have demonstrated an association between decreased vitamin D level and risk of multiple sclerosis (MS); however, it remains unclear whether this relationship is causal. We undertook a Mendelian randomization (MR) study to evaluate whether genetically lowered vitamin D level influences the risk of MS.\\n\\nMETHODS AND FINDINGS: We identified single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D (25OHD) level from SUNLIGHT, the largest (n = 33,996) genome-wide association study to date for vitamin D. Four SNPs were genome-wide significant for 25OHD level (p-values ranging from 6 × 10-10 to 2 × 10-109), and all four SNPs lay in, or near, genes strongly implicated in separate mechanisms influencing 25OHD. We then ascertained their effect on 25OHD level in 2,347 participants from a population-based cohort, the Canadian Multicentre Osteoporosis Study, and tested the extent to which the 25OHD-decreasing alleles explained variation in 25OHD level. We found that the count of 25OHD-decreasing alleles across these four SNPs was strongly associated with lower 25OHD level (n = 2,347, F-test statistic = 49.7, p = 2.4 × 10-12). Next, we conducted an MR study to describe the effect of genetically lowered 25OHD on the odds of MS in the International Multiple Sclerosis Genetics Consortium study, the largest genetic association study to date for MS (including up to 14,498 cases and 24,091 healthy controls). Alleles were weighted by their relative effect on 25OHD level, and sensitivity analyses were performed to test MR assumptions. MR analyses found that each genetically determined one-standard-deviation decrease in log-transformed 25OHD level conferred a 2.0-fold increase in the odds of MS (95% CI: 1.7-2.5; p = 7.7 × 10-12; I2 = 63%, 95% CI: 0%-88%). This result persisted in sensitivity analyses excluding SNPs possibly influenced by population stratification or pleiotropy (odds ratio [OR] = 1.7, 95% CI: 1.3-2.2; p = 2.3 × 10-5; I2 = 47%, 95% CI: 0%-85%) and including only SNPs involved in 25OHD synthesis or metabolism (ORsynthesis = 2.1, 95% CI: 1.6-2.6, p = 1 × 10-9; ORmetabolism = 1.9, 95% CI: 1.3-2.7, p = 0.002). While these sensitivity analyses decreased the possibility that pleiotropy may have biased the results, residual pleiotropy is difficult to exclude entirely.\\n\\nCONCLUSIONS: A genetically lowered 25OHD level is strongly associated with increased susceptibility to MS. Whether vitamin D sufficiency can delay, or prevent, MS onset merits further investigation in long-term randomized controlled trials.", "link"=>"http://www.mendeley.com/research/vitamin-d-risk-multiple-sclerosis-mendelian-randomization-study-4", "reader_count"=>157, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>32, "Student > Doctoral Student"=>11, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>8, "Student > Master"=>24, "Other"=>18, "Student > Bachelor"=>26, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>32, "Student > Doctoral Student"=>11, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>8, "Student > Master"=>24, "Other"=>18, "Student > Bachelor"=>26, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Agricultural and Biological Sciences"=>39, "Arts and Humanities"=>1, "Chemistry"=>1, "Computer Science"=>2, "Decision Sciences"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>11, "Nursing and Health Professions"=>6, "Mathematics"=>1, "Medicine and Dentistry"=>62, "Neuroscience"=>14, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>4, "Social Sciences"=>1, "Immunology and Microbiology"=>4, "Energy"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>62}, "Social Sciences"=>{"Social Sciences"=>1}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Psychology"=>{"Psychology"=>4}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>4}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Neuroscience"=>{"Neuroscience"=>14}, "Energy"=>{"Energy"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>39}, "Computer Science"=>{"Computer Science"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>11}}, "reader_count_by_country"=>{"Greece"=>1, "Canada"=>2, "Netherlands"=>1, "United States"=>1, "Brazil"=>1, "United Kingdom"=>1, "France"=>1, "Australia"=>1, "Chile"=>1, "Iceland"=>1}, "group_count"=>8}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2224721"], "description"=>"<p><sup>a</sup>OR is expressed as the odds of MS for a 1-SD decrease in natural-log-transformed 25OHD level. Note that the 95% CI for the <i>I</i><sup>2</sup> cannot be properly estimated given that there are only two SNPs per model.</p><p>Mendelian randomization estimate of the association of decreased 25OHD with the risk of multiple sclerosis stratified by SNPs near genes involved in 25OHD synthesis versus metabolism using a fixed-effects model.</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520213, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.t004", "stats"=>{"downloads"=>4, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mendelian_randomization_estimate_of_the_association_of_decreased_25OHD_with_the_risk_of_multiple_sclerosis_stratified_by_SNPs_near_genes_involved_in_25OHD_synthesis_versus_metabolism_using_a_fixed_effects_model_/1520213", "title"=>"Mendelian randomization estimate of the association of decreased 25OHD with the risk of multiple sclerosis stratified by SNPs near genes involved in 25OHD synthesis versus metabolism using a fixed-effects model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224720"], "description"=>"<p><sup>a</sup>OR is expressed as the odds of MS for a 1-SD decrease in natural-log-transformed 25OHD level.</p><p>Mendelian randomization estimate of the association of decreased 25OHD with the risk of multiple sclerosis excluding the <i>DHCR7</i> locus.</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520212, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.t003", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mendelian_randomization_estimate_of_the_association_of_decreased_25OHD_with_the_risk_of_multiple_sclerosis_excluding_the_DHCR7_locus_/1520212", "title"=>"Mendelian randomization estimate of the association of decreased 25OHD with the risk of multiple sclerosis excluding the <i>DHCR7</i> locus.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224717"], "description"=>"<p>Estimates obtained using a fixed-effects model.</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520209, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.g004", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mendelian_randomization_estimate_of_the_association_of_25OHD_level_with_risk_of_multiple_sclerosis_/1520209", "title"=>"Mendelian randomization estimate of the association of 25OHD level with risk of multiple sclerosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224713"], "description"=>"<p>Here we show the box-plot of natural-log-transformed 25OHD by the count of 25OHD-decreasing alleles in the CaMos population. A count of zero represents individuals with no 25OHD-decreasing alleles (or homozygous at each loci for the 25OHD-increasing allele), and a count of six represents an individual with six 25OHD-decreasing alleles. No individuals with a count of seven or more 25OHD-decreasing alleles were observed in this cohort. The center line and error bars represent the mean level of natural-log-transformed 25OHD and its 95% CI for each respective allele count. Note a negative trend between allele count and mean natural-log-transformed 25OHD.</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520207, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.g003", "stats"=>{"downloads"=>2, "page_views"=>47, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_25OHD_level_by_number_of_25OHD_decreasing_alleles_in_the_CaMos_cohort_/1520207", "title"=>"25OHD level by number of 25OHD-decreasing alleles in the CaMos cohort.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224712"], "description"=>"<p>In blue are the genes containing, or in proximity to, SNPs that were genome-wide significant for 25OHD level in SUNLIGHT (<i>n</i> = 33,996). The <i>p</i>-values for the association with 25OHD level were 1.9 × 10<sup>−109</sup> for <i>GC</i>, 2.1 × 10<sup>−27</sup> for <i>DHCR7</i>, 3.3 × 10<sup>−20</sup> for <i>CYP2R1</i>, and 6.0 × 10<sup>−10</sup> for <i>CYP24A1</i>. Note that each gene plays an independent role in modulating the level of 25OHD. Kidney and liver images credit: <a href=\"https://openclipart.org/\" target=\"_blank\">https://openclipart.org/</a>.</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520206, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.g002", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vitamin_D_pathway_/1520206", "title"=>"Vitamin D pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224709"], "description"=>"<p>The leftmost box lists SNPs that were genome-wide significant for 25OHD level in SUNLIGHT (<i>n</i> = 33,996). The blue arrow represents the effect of SNPs on multiply adjusted natural-log-transformed 25OHD level using data from CaMos (<i>n</i> = 2,347). The green arrow represents the causal association of decreased 25OHD level with the risk of MS using data from the largest genetic association study to date for MS (the IMSGC Immunochip study, up to 14,498 cases and 24,091 healthy controls).</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520203, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.g001", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_representation_of_Mendelian_randomization_analysis_/1520203", "title"=>"Schematic representation of Mendelian randomization analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224723", "https://ndownloader.figshare.com/files/2224724", "https://ndownloader.figshare.com/files/2224725", "https://ndownloader.figshare.com/files/2224726", "https://ndownloader.figshare.com/files/2224727", "https://ndownloader.figshare.com/files/2224728", "https://ndownloader.figshare.com/files/2224729", "https://ndownloader.figshare.com/files/2224730"], "description"=>"<div><p>Background</p><p>Observational studies have demonstrated an association between decreased vitamin D level and risk of multiple sclerosis (MS); however, it remains unclear whether this relationship is causal. We undertook a Mendelian randomization (MR) study to evaluate whether genetically lowered vitamin D level influences the risk of MS.</p><p>Methods and Findings</p><p>We identified single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D (25OHD) level from SUNLIGHT, the largest (<i>n</i> = 33,996) genome-wide association study to date for vitamin D. Four SNPs were genome-wide significant for 25OHD level (<i>p</i>-values ranging from 6 × 10<sup>−10</sup> to 2 × 10<sup>−109</sup>), and all four SNPs lay in, or near, genes strongly implicated in separate mechanisms influencing 25OHD. We then ascertained their effect on 25OHD level in 2,347 participants from a population-based cohort, the Canadian Multicentre Osteoporosis Study, and tested the extent to which the 25OHD-decreasing alleles explained variation in 25OHD level. We found that the count of 25OHD-decreasing alleles across these four SNPs was strongly associated with lower 25OHD level (<i>n</i> = 2,347, F-test statistic = 49.7, <i>p</i> = 2.4 × 10<sup>−12</sup>). Next, we conducted an MR study to describe the effect of genetically lowered 25OHD on the odds of MS in the International Multiple Sclerosis Genetics Consortium study, the largest genetic association study to date for MS (including up to 14,498 cases and 24,091 healthy controls). Alleles were weighted by their relative effect on 25OHD level, and sensitivity analyses were performed to test MR assumptions. MR analyses found that each genetically determined one-standard-deviation decrease in log-transformed 25OHD level conferred a 2.0-fold increase in the odds of MS (95% CI: 1.7–2.5; <i>p</i> = 7.7 × 10<sup>−12</sup>; <i>I</i><sup>2</sup> = 63%, 95% CI: 0%–88%). This result persisted in sensitivity analyses excluding SNPs possibly influenced by population stratification or pleiotropy (odds ratio [OR] = 1.7, 95% CI: 1.3–2.2; <i>p</i> = 2.3 × 10<sup>−5</sup>; <i>I</i><sup>2</sup> = 47%, 95% CI: 0%–85%) and including only SNPs involved in 25OHD synthesis or metabolism (OR<sub>synthesis</sub> = 2.1, 95% CI: 1.6–2.6, <i>p</i> = 1 × 10<sup>−9</sup>; OR<sub>metabolism</sub> = 1.9, 95% CI: 1.3–2.7, <i>p</i> = 0.002). While these sensitivity analyses decreased the possibility that pleiotropy may have biased the results, residual pleiotropy is difficult to exclude entirely.</p><p>Conclusions</p><p>A genetically lowered 25OHD level is strongly associated with increased susceptibility to MS. Whether vitamin D sufficiency can delay, or prevent, MS onset merits further investigation in long-term randomized controlled trials.</p></div>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520215, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001866.s001", "https://dx.doi.org/10.1371/journal.pmed.1001866.s002", "https://dx.doi.org/10.1371/journal.pmed.1001866.s003", "https://dx.doi.org/10.1371/journal.pmed.1001866.s004", "https://dx.doi.org/10.1371/journal.pmed.1001866.s005", "https://dx.doi.org/10.1371/journal.pmed.1001866.s006", "https://dx.doi.org/10.1371/journal.pmed.1001866.s007", "https://dx.doi.org/10.1371/journal.pmed.1001866.s008"], "stats"=>{"downloads"=>24, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vitamin_D_and_Risk_of_Multiple_Sclerosis_A_Mendelian_Randomization_Study_/1520215", "title"=>"Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224722"], "description"=>"<p><sup><b>a</b></sup>Expressed as the equivalent of a natural-log-transformed SD increase in 25OHD on the nanomoles/liter scale.</p><p>Clinical equivalence of a 1-SD natural-log increase in 25OHD for various vitamin D thresholds.</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520214, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.t005", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_equivalence_of_a_1_SD_natural_log_increase_in_25OHD_for_various_vitamin_D_thresholds_/1520214", "title"=>"Clinical equivalence of a 1-SD natural-log increase in 25OHD for various vitamin D thresholds.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224719"], "description"=>"<p><sup>a</sup>OR is expressed as the odds of MS for a 1-SD decrease in natural-log-transformed 25OHD level.</p><p>Mendelian randomization estimate of the association of decreased 25OHD with the risk of multiple sclerosis.</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520211, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.t002", "stats"=>{"downloads"=>5, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mendelian_randomization_estimate_of_the_association_of_decreased_25OHD_with_the_risk_of_multiple_sclerosis_/1520211", "title"=>"Mendelian randomization estimate of the association of decreased 25OHD with the risk of multiple sclerosis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-25 04:10:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/2224718"], "description"=>"<p>Estimates obtained using a fixed-effects model.</p>", "links"=>[], "tags"=>["Canadian Multicentre Osteoporosis Study", "sensitivity analyses", "International Multiple Sclerosis Genetics Consortium study", "sunlight", "snp", "25 OHD level", "vitamin D level influences", "vitamin D level", "Mendelian Randomization Study BackgroundObservational studies", "25 OHD", "vitamin D sufficiency", "MS onset merits", "ci", "test MR assumptions", "25 OHD synthesis"], "article_id"=>1520210, "categories"=>["Uncategorised"], "users"=>["Lauren E. Mokry", "Stephanie Ross", "Omar S. Ahmad", "Vincenzo Forgetta", "George Davey Smith", "Aaron Leong", "Celia M. T. Greenwood", "George Thanassoulis", "J. Brent Richards"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001866.g005", "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mendelian_randomization_estimate_of_the_association_of_25OHD_level_with_risk_of_multiple_sclerosis_excluding_the_DHCR7_locus_/1520210", "title"=>"Mendelian randomization estimate of the association of 25OHD level with risk of multiple sclerosis excluding the <i>DHCR7</i> locus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-25 04:10:25"}

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  • {"unique-ip"=>"30", "full-text"=>"30", "pdf"=>"18", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"56", "full-text"=>"69", "pdf"=>"15", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"19", "supp-data"=>"15", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"29", "full-text"=>"20", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"30", "full-text"=>"31", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"39", "full-text"=>"49", "pdf"=>"13", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"2", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"49", "full-text"=>"61", "pdf"=>"21", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"41", "full-text"=>"46", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"30", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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