{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:21:56Z","timestamp":1777983716927,"version":"3.51.4"},"reference-count":19,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["grant no. 21173, 21754 and 21755"],"award-info":[{"award-number":["grant no. 21173, 21754 and 21755"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Scleroderma and Related Disorders"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction\/Objectives:<\/jats:title>\n                    <jats:p>Raynaud\u2019s phenomenon is a common vasospastic disorder associated with reduced health-related quality of life and, occasionally, ischaemic tissue damage depending on aetiology. The effect of beta-1-adrenoceptor blockers (e.g. bisoprolol, atenolol) on Raynaud\u2019s phenomenon remains unclear. We aimed to assess the association between genetically mimicked beta-1-adrenoceptor blockade and the risk of Raynaud\u2019s phenomenon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We used two protein-coding single nucleotide polymorphisms in the\n                      <jats:italic>ADRB1<\/jats:italic>\n                      gene, rs1801252 (A\u2009&gt;\u2009G; Ser49Gly) and rs1801253 (G\u2009&gt;\u2009C; Arg389Gly), to derive an unweighted allele count as the instrumental variable, using individual-level UK Biobank data. Raynaud\u2019s phenomenon was defined using International Classification of Diseases or Read codes. We used the ratio method and analysis was performed separately using systolic and diastolic blood pressure as the biomarker. To examine the validity of this approach and the Raynaud\u2019s phenomenon case definition, we also tested the known association between phosphodiesterase-5 inhibition and Raynaud\u2019s phenomenon risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Analysis included 4743 individuals with Raynaud\u2019s phenomenon (mean age 58\u2009years, 68% female) and 403,762 controls. There was no evidence of an effect of genetically mimicked beta-1-adrenoreceptor blockade on the risk of Raynaud\u2019s phenomenon, using systolic blood pressure (odds ratio = 0.93 per mmHg reduction; 95% confidence interval = [0.83, 1.04]; p\u2009=\u20090.19) or diastolic blood pressure (odds ratio = 0.91 per mmHg reduction; 95% confidence interval = [0.78, 1.05]; p\u2009=\u20090.19). The positive control exposure phosphodiesterase-5 inhibition was associated with reduced Raynaud\u2019s phenomenon risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We found no genetic evidence to support a causal association between beta-1-adrenoceptor blockade and Raynaud\u2019s phenomenon risk in either direction. Randomised controlled trials are required to confirm the safety of beta-1-adrenoceptor blockers in people with Raynaud\u2019s phenomenon.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/23971983241312543","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T22:21:24Z","timestamp":1742941284000},"page":"151-155","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between beta-1-adrenoceptor blockade and risk of Raynaud\u2019s phenomenon: Mendelian randomisation study"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3737-557X","authenticated-orcid":false,"given":"Jacob C","family":"Williams","sequence":"first","affiliation":[{"name":"St James\u2019s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK"},{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kira","family":"Rogers","sequence":"additional","affiliation":[{"name":"Manchester Medical School, The University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Coulson","sequence":"additional","affiliation":[{"name":"Manchester Medical School, The University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, UK"},{"name":"Division of Musculoskeletal and Dermatological Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-7353","authenticated-orcid":false,"given":"Sizheng Steven","family":"Zhao","sequence":"additional","affiliation":[{"name":"Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, The University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2024.152521"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-019-04745-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X17740074"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0386-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/0003319711432861"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109039"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(87)90023-9"},{"issue":"6","key":"e_1_3_2_9_2","first-page":"767","article-title":"The importance of presynaptic beta receptors in Raynaud\u2019s disease","volume":"9","author":"Brotzu G","year":"1989","unstructured":"Brotzu G, Falchi S, Mannu B, et al. The importance of presynaptic beta receptors in Raynaud\u2019s disease. J Vasc Surg 1989; 9(6): 767\u2013771.","journal-title":"J Vasc Surg"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2011.04.004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X9700200404"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.6024.1498"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1979.tb00953.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.72.3.466"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1992.tb05777.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S75482"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.16544.1"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00549-w"},{"key":"e_1_3_2_20_2","article-title":"A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: Mendelian randomisation study","volume":"383","author":"Woolf B","year":"2023","unstructured":"Woolf B, Rajasundaram S, Cronj\u00e9 HT, et al. A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: Mendelian randomisation study. 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