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To assess if platelet count mediated the effect, we then performed a two\u2010step MR study. Putative associations (GPIb\u03b1\/platelet count\/disease) detected by MR analyses were subsequently assessed using multiple\u2010trait colocalization analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After correction for multiple testing (Bonferroni\u2010corrected threshold <jats:italic>P<\/jats:italic> \u2264 2 \u00d7 10<jats:sup>\u22123<\/jats:sup>), GPIb\u03b1, instrumented by either <jats:italic>cis<\/jats:italic>\u2010pQTL or <jats:italic>trans<\/jats:italic>\u2010pQTL, was causally implicated with an increased risk of oligoarticular and rheumatoid factor (RF)\u2013negative polyarticular juvenile idiopathic arthritis (JIA). These effects of GPIb\u03b1 appeared to be mediated by platelet count and were supported by strong evidence of colocalization (probability of all 3 traits sharing a common causal variant \u22650.80). GPIb\u03b1 instrumented by <jats:italic>cis<\/jats:italic>\u2010pQTL did not appear to affect cardiovascular risk, although the GPIb\u03b1 <jats:italic>trans<\/jats:italic>\u2010pQTL was associated with an increased risk of cardiovascular diseases and autoimmune diseases but a decreased risk of autoinflammatory diseases, suggesting that this <jats:italic>trans\u2010<\/jats:italic>acting instrument operates through other pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The role of platelets in thrombosis is well\u2010established; however, our findings provide some novel genetic evidence that platelets may be causally implicated in the development of oligoarticular and RF\u2010negative polyarticular JIA, and indicate that GPIb\u03b1 may serve as a putative therapeutic target for these JIA subtypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41561","type":"journal-article","created":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T13:00:47Z","timestamp":1603198847000},"page":"693-701","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Platelet Glycoprotein Ib \u03b1\u2010Chain as a Putative Therapeutic Target for Juvenile Idiopathic Arthritis: A Mendelian Randomization Study"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3368-9935","authenticated-orcid":false,"given":"Shan","family":"Luo","sequence":"first","affiliation":[{"name":"The University of Hong Kong, Hong Kong, China, and University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7385-6307","authenticated-orcid":false,"given":"Sarah L. 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