{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T05:01:55Z","timestamp":1786770115338,"version":"build-2736575974"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["starting grant 2018-02247"],"award-info":[{"award-number":["starting grant 2018-02247"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K99\/R00AG054573"],"award-info":[{"award-number":["K99\/R00AG054573"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vitamin D has been associated with a variety of human complex traits and diseases in observational studies, but a causal relationship remains unclear. To examine a putative causal effect of vitamin D across phenotypic domains and disease categories, we conducted Mendelian randomization (MR) analyses using genetic instruments associated with circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We leveraged genome-wide significant 25(OH)D-associated SNPs (N\u2009=\u2009138) from a meta-analysis combining a vitamin D GWAS conducted in 401,460 white British UK Biobank (UKBB) participants and an independent vitamin D GWAS including 42,274 samples of European ancestry, and examined 190 large-scale health-related GWAS spanning a broad spectrum of complex traits, diseases and biomarkers. We applied multiple MR methods to estimate the causal effect of vitamin D while testing and controlling for potential biases from horizontal pleiotropy. Consistent with previous findings, genetically predicted increased 25(OH)D levels significantly decreased the risk of multiple sclerosis (OR\u2009=\u20090.824; 95% CI 0.689\u20130.986). The protective effect estimate was consistent across different MR methods and four different multiple sclerosis GWAS with varying sample sizes and genotyping platforms. On the contrary, we found limited evidence in support of a causal effect of 25(OH)D on anthropometric traits, obesity, cognitive function, sleep behavior, breast and prostate cancer, and autoimmune, cardiovascular, metabolic, neurological and psychiatric traits and diseases, and blood biomarkers. Our results may inform ongoing and future randomized clinical trials of vitamin D supplementation.<\/jats:p>","DOI":"10.1038\/s41598-020-80655-w","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T06:19:34Z","timestamp":1610086774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study"],"prefix":"10.1038","volume":"11","author":[{"given":"Xia","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"80655_CR1","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/S0030-5898(20)31262-1","volume":"15","author":"SH Doppelt","year":"1984","unstructured":"Doppelt, S. H. Vitamin D, rickets, and osteomalacia. Orthop. Clin. North Am. 15, 671\u2013686 (1984).","journal-title":"Orthop. Clin. North Am."},{"key":"80655_CR2","doi-asserted-by":"crossref","unstructured":"Scaranti, M., J\u00fanior, G. de C. & Hoff, A. O. Vitamin D and cancer: does it really matter? Curr. Opin. Oncol. 28, 205 (2016).","DOI":"10.1097\/CCO.0000000000000282"},{"key":"80655_CR3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s11154-016-9405-9","volume":"18","author":"B Altieri","year":"2017","unstructured":"Altieri, B. et al. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept. Rev. Endocr. Metab. Disord. 18, 335\u2013346 (2017).","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"80655_CR4","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3390\/nu9070651","volume":"9","author":"PHF Gois","year":"2017","unstructured":"Gois, P. H. F., Ferreira, D., Olenski, S. & Seguro, A. C. Vitamin D and infectious diseases: Simple bystander or contributing factor?. Nutrients 9, 2 (2017).","journal-title":"Nutrients"},{"key":"80655_CR5","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jacc.2017.05.031","volume":"70","author":"I Al Mheid","year":"2017","unstructured":"Al Mheid, I. & Quyyumi, A. A. Vitamin D and cardiovascular disease: Controversy unresolved. J. Am. Coll. Cardiol. 70, 89\u2013100 (2017).","journal-title":"J. Am. Coll. Cardiol."},{"key":"80655_CR6","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/978-3-319-56017-5_16","volume":"996","author":"CM Issa","year":"2017","unstructured":"Issa, C. M. Vitamin D and type 2 diabetes mellitus. Adv. Exp. Med. Biol. 996, 193\u2013205 (2017).","journal-title":"Adv. Exp. Med. Biol."},{"key":"80655_CR7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.cct.2011.09.009","volume":"33","author":"JE Manson","year":"2012","unstructured":"Manson, J. E. et al. The VITamin D and OmegA-3 TriaL (VITAL): Rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp. Clin. Trials 33, 159\u2013171 (2012).","journal-title":"Contemp. Clin. Trials"},{"key":"80655_CR8","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.cct.2016.04.005","volume":"48","author":"RE Neale","year":"2016","unstructured":"Neale, R. E. et al. The D-health trial: A randomized trial of vitamin D for prevention of mortality and cancer. Contemp. Clin. Trials 48, 83\u201390 (2016).","journal-title":"Contemp. Clin. Trials"},{"key":"80655_CR9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1056\/NEJMoa1809944","volume":"380","author":"JE Manson","year":"2019","unstructured":"Manson, J. E. et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N. Engl. J. Med. 380, 33\u201344 (2019).","journal-title":"N. Engl. J. Med."},{"key":"80655_CR10","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1001\/jama.2020.10224","volume":"324","author":"OI Okereke","year":"2020","unstructured":"Okereke, O. I. et al. Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: A randomized clinical trial. JAMA 324, 471\u2013480 (2020).","journal-title":"JAMA"},{"key":"80655_CR11","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/S0140-6736(10)60588-0","volume":"376","author":"TJ Wang","year":"2010","unstructured":"Wang, T. J. et al. Common genetic determinants of vitamin D insufficiency: A genome-wide association study. Lancet 376, 180\u2013188 (2010).","journal-title":"Lancet"},{"key":"80655_CR12","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/s41467-017-02662-2","volume":"9","author":"X Jiang","year":"2018","unstructured":"Jiang, X. et al. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nat. Commun. 9, 260 (2018).","journal-title":"Nat. Commun."},{"key":"80655_CR13","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.ajhg.2020.01.017","volume":"106","author":"D Manousaki","year":"2020","unstructured":"Manousaki, D. et al. Genome-wide association study for vitamin D levels reveals 69 independent loci. Am. J. Hum. Genet. 106, 327\u2013337 (2020).","journal-title":"Am. J. Hum. Genet."},{"key":"80655_CR14","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1038\/s41467-020-15421-7","volume":"11","author":"JA Revez","year":"2020","unstructured":"Revez, J. A. et al. Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration. Nat. Commun. 11, 1647 (2020).","journal-title":"Nat. Commun."},{"key":"80655_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","volume":"32","author":"G Davey Smith","year":"2003","unstructured":"Davey Smith, G. & Ebrahim, S. \u2018Mendelian randomization\u2019: Can genetic epidemiology contribute to understanding environmental determinants of disease?. Int. J. Epidemiol. 32, 1\u201322 (2003).","journal-title":"Int. J. Epidemiol."},{"key":"80655_CR16","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1097\/EDE.0000000000000081","volume":"25","author":"TJ VanderWeele","year":"2014","unstructured":"VanderWeele, T. J., Tchetgen Tchetgen, E. J., Cornelis, M. & Kraft, P. Methodological challenges in mendelian randomization. Epidemiology 25, 427\u2013435 (2014).","journal-title":"Epidemiology"},{"key":"80655_CR17","doi-asserted-by":"publisher","first-page":"e1001866","DOI":"10.1371\/journal.pmed.1001866","volume":"12","author":"LE Mokry","year":"2015","unstructured":"Mokry, L. E. et al. Vitamin D and risk of multiple sclerosis: A mendelian randomization study. PLOS Med. 12, e1001866 (2015).","journal-title":"PLOS Med."},{"key":"80655_CR18","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1212\/NXG.0000000000000097","volume":"2","author":"B Rhead","year":"2016","unstructured":"Rhead, B. et al. Mendelian randomization shows a causal effect of low vitamin D on multiple sclerosis risk. Neurol. Genet. 2, e97 (2016).","journal-title":"Neurol. Genet."},{"key":"80655_CR19","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1212\/WNL.0000000000003849","volume":"88","author":"MA Gianfrancesco","year":"2017","unstructured":"Gianfrancesco, M. A. et al. Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS. Neurology 88, 1623\u20131629 (2017).","journal-title":"Neurology"},{"key":"80655_CR20","doi-asserted-by":"publisher","first-page":"2567","DOI":"10.1212\/WNL.0000000000003430","volume":"87","author":"LE Mokry","year":"2016","unstructured":"Mokry, L. E. et al. Genetically decreased vitamin D and risk of Alzheimer disease. Neurology 87, 2567\u20132574 (2016).","journal-title":"Neurology"},{"key":"80655_CR21","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3390\/nu10091243","volume":"10","author":"SC Larsson","year":"2018","unstructured":"Larsson, S. C., Traylor, M., Markus, H. S. & Micha\u00eblsson, K. Serum parathyroid hormone, 25-hydroxyvitamin D, and risk of Alzheimer\u2019s disease: A mendelian randomization study. Nutrients 10, 2 (2018).","journal-title":"Nutrients"},{"key":"80655_CR22","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/S2213-8587(14)70113-5","volume":"2","author":"KS Vimaleswaran","year":"2014","unstructured":"Vimaleswaran, K. S. et al. Association of vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study. Lancet Diabetes Endocrinol. 2, 719\u2013729 (2014).","journal-title":"Lancet Diabetes Endocrinol."},{"key":"80655_CR23","doi-asserted-by":"publisher","first-page":"g6330","DOI":"10.1136\/bmj.g6330","volume":"349","author":"S Afzal","year":"2014","unstructured":"Afzal, S., Br\u00f8ndum-Jacobsen, P., Bojesen, S. E. & Nordestgaard, B. G. Genetically low vitamin D concentrations and increased mortality: Mendelian randomisation analysis in three large cohorts. BMJ 349, g6330 (2014).","journal-title":"BMJ"},{"key":"80655_CR24","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1093\/ije\/dyw207","volume":"45","author":"J-S Ong","year":"2016","unstructured":"Ong, J.-S. et al. Association of vitamin D levels and risk of ovarian cancer: A Mendelian randomization study. Int. J. Epidemiol. 45, 1619\u20131630 (2016).","journal-title":"Int. J. Epidemiol."},{"key":"80655_CR25","doi-asserted-by":"publisher","first-page":"j4761","DOI":"10.1136\/bmj.j4761","volume":"359","author":"VI Dimitrakopoulou","year":"2017","unstructured":"Dimitrakopoulou, V. I. et al. Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study. BMJ 359, j4761 (2017).","journal-title":"BMJ"},{"key":"80655_CR26","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/s41588-018-0144-6","volume":"50","author":"P-R Loh","year":"2018","unstructured":"Loh, P.-R., Kichaev, G., Gazal, S., Schoech, A. P. & Price, A. L. Mixed-model association for biobank-scale datasets. Nat. Genet. 50, 906\u2013908 (2018).","journal-title":"Nat. Genet."},{"key":"80655_CR27","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","volume":"88","author":"J Yang","year":"2011","unstructured":"Yang, J., Hong Lee, S., Goddard, M. E. & Visscher, P. M. GCTA: A tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76\u201382 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"80655_CR28","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","volume":"44","author":"J Bowden","year":"2015","unstructured":"Bowden, J., Davey Smith, G. & Burgess, S. Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression. Int. J. Epidemiol. 44, 512\u2013525 (2015).","journal-title":"Int. J. Epidemiol."},{"key":"80655_CR29","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck, M., Chen, C.-Y., Neale, B. & Do, R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat. Genet. 50, 693\u2013698 (2018).","journal-title":"Nat. Genet."},{"key":"80655_CR30","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","volume":"40","author":"J Bowden","year":"2016","unstructured":"Bowden, J., Smith, G. D., Haycock, P. C. & Burgess, S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol. 40, 304\u2013314 (2016).","journal-title":"Genet. Epidemiol."},{"key":"80655_CR31","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1093\/ije\/dyy258","volume":"48","author":"J Bowden","year":"2019","unstructured":"Bowden, J. et al. Improving the accuracy of two-sample summary-data Mendelian randomization: Moving beyond the NOME assumption. Int. J. Epidemiol. 48, 728\u2013742 (2019).","journal-title":"Int. J. Epidemiol."},{"key":"80655_CR32","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1183\/09031936.00029011","volume":"38","author":"EM Hollams","year":"2011","unstructured":"Hollams, E. M. et al. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur. Respir. J. 38, 1320\u20131327 (2011).","journal-title":"Eur. Respir. J."},{"key":"80655_CR33","doi-asserted-by":"publisher","first-page":"e1001383","DOI":"10.1371\/journal.pmed.1001383","volume":"10","author":"KS Vimaleswaran","year":"2013","unstructured":"Vimaleswaran, K. S. et al. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 10, e1001383 (2013).","journal-title":"PLoS Med."},{"key":"80655_CR34","doi-asserted-by":"publisher","first-page":"3267","DOI":"10.1210\/jc.2018-00250","volume":"103","author":"J Lund-Nielsen","year":"2018","unstructured":"Lund-Nielsen, J. et al. Vitamin D and inflammatory bowel disease: Mendelian randomization analyses in the copenhagen studies and UK biobank. J. Clin. Endocrinol. Metab. 103, 3267\u20133277 (2018).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"80655_CR35","doi-asserted-by":"publisher","first-page":"e1002294","DOI":"10.1371\/journal.pmed.1002294","volume":"14","author":"D Manousaki","year":"2017","unstructured":"Manousaki, D. et al. Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study. PLOS Med. 14, e1002294 (2017).","journal-title":"PLOS Med."},{"key":"80655_CR36","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.1007\/s10067-018-4152-9","volume":"37","author":"S-C Bae","year":"2018","unstructured":"Bae, S.-C. & Lee, Y. H. Vitamin D level and risk of systemic lupus erythematosus and rheumatoid arthritis: A Mendelian randomization. Clin. Rheumatol. 37, 2415\u20132421 (2018).","journal-title":"Clin. Rheumatol."},{"key":"80655_CR37","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1161\/CIRCGENETICS.116.001396","volume":"9","author":"D Manousaki","year":"2016","unstructured":"Manousaki, D., Mokry, L. E., Ross, S., Goltzman, D. & Brent, R. J. Mendelian randomization studies do not support a role for vitamin D in coronary artery disease. Circ. Cardiovasc. Genet. 9, 349\u2013356 (2016).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"80655_CR38","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1093\/ije\/dyv078","volume":"44","author":"P Brondum-Jacobsen","year":"2015","unstructured":"Brondum-Jacobsen, P., Benn, M., Afzal, S. & Nordestgaard, B. G. No evidence that genetically reduced 25-hydroxyvitamin D is associated with increased risk of ischaemic heart disease or myocardial infarction: A Mendelian randomization study. Int. J. Epidemiol. 44, 651\u2013661 (2015).","journal-title":"Int. J. Epidemiol."},{"key":"80655_CR39","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1161\/CIRCGENETICS.113.000416","volume":"7","author":"EM Ooi","year":"2014","unstructured":"Ooi, E. M., Afzal, S. & Nordestgaard, B. G. Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population. Circ. Cardiovasc. Genet. 7, 650\u2013658 (2014).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"80655_CR40","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/S2213-8587(13)70200-6","volume":"2","author":"S Afzal","year":"2014","unstructured":"Afzal, S., Br\u00f8ndum-Jacobsen, P., Bojesen, S. E. & Nordestgaard, B. G. Vitamin D concentration, obesity, and risk of diabetes: A mendelian randomisation study. Lancet Diabet. Endocrinol. 2, 298\u2013306 (2014).","journal-title":"Lancet Diabet. Endocrinol."},{"key":"80655_CR41","doi-asserted-by":"publisher","first-page":"e1002566","DOI":"10.1371\/journal.pmed.1002566","volume":"15","author":"L Lu","year":"2018","unstructured":"Lu, L. et al. Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults. PLOS Med. 15, e1002566 (2018).","journal-title":"PLOS Med."},{"key":"80655_CR42","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/ejcn.2013.233","volume":"68","author":"LLN Husemoen","year":"2014","unstructured":"Husemoen, L. L. N. et al. Investigating the causal effect of vitamin D on serum adiponectin using a mendelian randomization approach. Eur. J. Clin. Nutr. 68, 189\u2013195 (2014).","journal-title":"Eur. J. Clin. Nutr."},{"key":"80655_CR43","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1093\/ije\/dyy284","volume":"48","author":"X Jiang","year":"2019","unstructured":"Jiang, X. et al. Circulating vitamin D concentrations and risk of breast and prostate cancer: A Mendelian randomization study. Int. J. Epidemiol. 48, 1416\u20131424 (2019).","journal-title":"Int. J. Epidemiol."},{"key":"80655_CR44","doi-asserted-by":"publisher","first-page":"13230","DOI":"10.1038\/s41598-017-13189-3","volume":"7","author":"J Maddock","year":"2017","unstructured":"Maddock, J. et al. Vitamin D and cognitive function: A Mendelian randomisation study. Sci. Rep. 7, 13230 (2017).","journal-title":"Sci. Rep."},{"key":"80655_CR45","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.3390\/nu10121987","volume":"10","author":"K Micha\u00eblsson","year":"2018","unstructured":"Micha\u00eblsson, K., Melhus, H. & Larsson, S. Serum 25-hydroxyvitamin D concentrations and major depression: A Mendelian randomization study. Nutrients 10, 1987 (2018).","journal-title":"Nutrients"},{"key":"80655_CR46","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/gepi.21998","volume":"40","author":"S Burgess","year":"2016","unstructured":"Burgess, S., Davies, N. M. & Thompson, S. G. Bias due to participant overlap in two-sample Mendelian randomization. Genet. Epidemiol. 40, 597\u2013608 (2016).","journal-title":"Genet. Epidemiol."},{"key":"80655_CR47","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1214\/19-AOS1866","volume":"48","author":"Q Zhao","year":"2020","unstructured":"Zhao, Q., Wang, J., Hemani, G., Bowden, J. & Small, D. S. Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score. Ann. Stat. 48, 1742\u20131769 (2020).","journal-title":"Ann. Stat."},{"key":"80655_CR48","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/s41588-020-0631-4","volume":"52","author":"J Morrison","year":"2020","unstructured":"Morrison, J., Knoblauch, N., Marcus, J. H., Stephens, M. & He, X. Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics. Nat. Genet. 52, 740\u2013747 (2020).","journal-title":"Nat. Genet."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80655-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80655-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80655-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T06:16:19Z","timestamp":1674800179000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80655-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["80655"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-80655-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/677922","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]},"assertion":[{"value":"8 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"184"}}