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The MR-Base platform supports systematic causal inference across the human phenome.

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cam.issuedOnline2018-03-30
datacite.isderivedfrom.doi10.1101/078972
datacite.isderivedfrom.doi10.7554/elife.34408.001
dc.contributor.authorHemani, Gibran
dc.contributor.authorZheng, Jie
dc.contributor.authorElsworth, Benjamin
dc.contributor.authorWade, Kaitlin H
dc.contributor.authorHaberland, Valeriia
dc.contributor.authorBaird, Denis
dc.contributor.authorLaurin, Charles
dc.contributor.authorBurgess, Stephen
dc.contributor.authorBowden, Jack
dc.contributor.authorLangdon, Ryan
dc.contributor.authorTan, Vanessa Y
dc.contributor.authorYarmolinsky, James
dc.contributor.authorShihab, Hashem A
dc.contributor.authorTimpson, Nicholas J
dc.contributor.authorEvans, David M
dc.contributor.authorRelton, Caroline
dc.contributor.authorMartin, Richard M
dc.contributor.authorDavey Smith, George
dc.contributor.authorGaunt, Tom R
dc.contributor.authorHaycock, Philip C
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
dc.date.accessioned2018-09-12T08:24:45Z
dc.date.available2018-09-12T08:24:45Z
dc.date.issued2018-05-30
dc.description.abstractResults from genome-wide association studies (GWAS) can be used to infer causal relationships between phenotypes, using a strategy known as 2-sample Mendelian randomization (2SMR) and bypassing the need for individual-level data. However, 2SMR methods are evolving rapidly and GWAS results are often insufficiently curated, undermining efficient implementation of the approach. We therefore developed MR-Base (<ext-link ext-link-type="uri" xlink:href="http://www.mrbase.org">http://www.mrbase.org</ext-link>): a platform that integrates a curated database of complete GWAS results (no restrictions according to statistical significance) with an application programming interface, web app and R packages that automate 2SMR. The software includes several sensitivity analyses for assessing the impact of horizontal pleiotropy and other violations of assumptions. The database currently comprises 11 billion single nucleotide polymorphism-trait associations from 1673 GWAS and is updated on a regular basis. Integrating data with software ensures more rigorous application of hypothesis-driven analyses and allows millions of potential causal relationships to be efficiently evaluated in phenome-wide association studies.
dc.description.sponsorshipSupported by Cancer Research UK grant C18281/A19169 (the Integrative Cancer Epidemiology Programme) and the Roy Castle Lung Cancer Foundation (2013/18/Relton). The Medical Research Council Integrative Epidemiology Unit is supported by grants MC_UU_12013/1, MC_UU_12013/2 and MC_UU_12013/8. PCH is supported by a Cancer Research UK Population Research Postdoctoral Fellowship (C52724/A20138). Jack Bowden is supported by a MRC Methodology Research Fellowship (grant MR/N501906/1). DME supported by the NHMRC APP1125200, APP1137714. GH is supported by Wellcome (208806/Z/17/Z).
dc.identifier.doi10.17863/CAM.27599
dc.identifier.eissn2050-084X
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280231
dc.languageeng
dc.language.isoeng
dc.publishereLife Sciences Publications
dc.publisher.urlhttps://elifesciences.org/articles/34408
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGWAS
dc.subjectMendelian randomization
dc.subjectcausal inference
dc.subjectcomputational biology
dc.subjecthuman
dc.subjecthuman biology
dc.subjectmedicine
dc.subjectsystems biology
dc.titleThe MR-Base platform supports systematic causal inference across the human phenome.
dc.typeArticle
dcterms.dateAccepted2018-03-28
prism.numbere34408
prism.publicationDate2018
prism.publicationNameeLife
prism.volume7
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MC_UU_00002/7)
pubs.funder-project-idWellcome Trust (204623/Z/16/Z)
rioxxterms.licenseref.startdate2018-05-30
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.7554/eLife.34408

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