{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T02:08:35Z","timestamp":1783908515485,"version":"3.55.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Tianjin Municipal Health and Wellness Science and Technology Project","award":["TJWJ2024ZD001"],"award-info":[{"award-number":["TJWJ2024ZD001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1007\/s00210-026-05275-z","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T02:22:30Z","timestamp":1775096550000},"page":"13831-13850","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring spinal degenerative diseases therapy targets through druggability genes: a Mendelian randomization study"],"prefix":"10.1007","volume":"399","author":[{"given":"Hao","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Diao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Rong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"issue":"7571","key":"5275_CR1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"1000 Genomes Project Consortium, Auton A, Brooks LD et al (2015) A global reference for human genetic variation. Nature 526(7571):68\u201374. https:\/\/doi.org\/10.1038\/nature15393","journal-title":"Nature"},{"issue":"41","key":"5275_CR2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000035461","volume":"102","author":"XH Bai","year":"2023","unstructured":"Bai XH, Su J, Mu YY et al (2023) Association between the ESR1 and ESR2 polymorphisms and osteoporosis risk: an updated meta-analysis. Medicine (Baltimore) 102(41):e35461. https:\/\/doi.org\/10.1097\/MD.0000000000035461","journal-title":"Medicine (Baltimore)"},{"issue":"7302","key":"5275_CR3","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature09204","volume":"466","author":"C Behrends","year":"2010","unstructured":"Behrends C, Sowa ME, Gygi SP, Harper JW (2010) Network organization of the human autophagy system. Nature 466(7302):68\u201376. https:\/\/doi.org\/10.1038\/nature09204","journal-title":"Nature"},{"issue":"2","key":"5275_CR4","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 (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44(2):512\u2013525. https:\/\/doi.org\/10.1093\/ije\/dyv080","journal-title":"Int J Epidemiol"},{"issue":"4","key":"5275_CR5","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","volume":"40","author":"J Bowden","year":"2016","unstructured":"Bowden J, Davey Smith G, Haycock PC, Burgess S (2016) Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 40(4):304\u2013314. https:\/\/doi.org\/10.1002\/gepi.21965","journal-title":"Genet Epidemiol"},{"issue":"3","key":"5275_CR6","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","volume":"40","author":"S Burgess","year":"2011","unstructured":"Burgess S, Thompson SG, CRP CHD Genetics Collaboration (2011) Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol 40(3):755\u2013764. https:\/\/doi.org\/10.1093\/ije\/dyr036","journal-title":"Int J Epidemiol"},{"issue":"5","key":"5275_CR7","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1177\/0962280215597579","volume":"26","author":"S Burgess","year":"2017","unstructured":"Burgess S, Small DS, Thompson SG (2017) A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res 26(5):2333\u20132355. https:\/\/doi.org\/10.1177\/0962280215597579","journal-title":"Stat Methods Med Res"},{"issue":"7726","key":"5275_CR8","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft C, Freeman C, Petkova D et al (2018) The UK biobank resource with deep phenotyping and genomic data. Nature 562(7726):203\u2013209. https:\/\/doi.org\/10.1038\/s41586-018-0579-z","journal-title":"Nature"},{"issue":"14","key":"5275_CR9","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1016\/j.febslet.2015.05.001","volume":"589","author":"CC Campa","year":"2015","unstructured":"Campa CC, Franco I, Hirsch E (2015) PI3K-C2 \u03b1: one enzyme for two products coupling vesicle trafficking and signal transduction. FEBS Lett 589(14):1552\u20131558. https:\/\/doi.org\/10.1016\/j.febslet.2015.05.001","journal-title":"FEBS Lett"},{"issue":"21","key":"5275_CR10","doi-asserted-by":"publisher","first-page":"7205","DOI":"10.26355\/eurrev_201811_16254","volume":"22","author":"LM Chao","year":"2018","unstructured":"Chao LM, Sun W, Chen H, Liu BY, Li PF, Zhao DW (2018) MicroRNA-31 inhibits osteosarcoma cell proliferation, migration and invasion by targeting PIK3C2A. Eur Rev Med Pharmacol Sci 22(21):7205\u20137213. https:\/\/doi.org\/10.26355\/eurrev_201811_16254","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"5275_CR11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.nut.2018.08.005","volume":"59","author":"R Costa de Miranda","year":"2019","unstructured":"Costa de Miranda R, Di Lorenzo N, Andreoli A et al (2019) Body composition and bone mineral density in Huntington\u2019s disease. Nutrition 59:145\u2013149. https:\/\/doi.org\/10.1016\/j.nut.2018.08.005","journal-title":"Nutrition"},{"key":"5275_CR12","doi-asserted-by":"publisher","unstructured":"Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J, et al (2013) Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials.\u00a0Lancet 382(9894):769\u2013779\u00a0https:\/\/doi.org\/10.1016\/S0140-6736(13)60900-9","DOI":"10.1016\/S0140-6736(13)60900-9"},{"issue":"10","key":"5275_CR13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076405","volume":"8","author":"K Devereaux","year":"2013","unstructured":"Devereaux K, Dall\u2019Armi C, Alcazar-Roman A et al (2013) Regulation of mammalian autophagy by class II and III PI 3-kinases through PI3P synthesis. PLoS One 8(10):e76405. https:\/\/doi.org\/10.1371\/journal.pone.0076405","journal-title":"PLoS One"},{"issue":"3","key":"5275_CR14","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1080\/14740338.2021.1965988","volume":"21","author":"MJ Domper Arnal","year":"2022","unstructured":"Domper Arnal MJ, Hijos-Mallada G, Lanas A (2022) Gastrointestinal and cardiovascular adverse events associated with NSAIDs. Expert Opin Drug Saf 21(3):373\u2013384. https:\/\/doi.org\/10.1080\/14740338.2021.1965988","journal-title":"Expert Opin Drug Saf"},{"issue":"3","key":"5275_CR15","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1042\/BJ20120008","volume":"443","author":"M Falasca","year":"2012","unstructured":"Falasca M, Maffucci T (2012) Regulation and cellular functions of class II phosphoinositide 3-kinases. Biochem J 443(3):587\u2013601. https:\/\/doi.org\/10.1042\/BJ20120008","journal-title":"Biochem J"},{"issue":"383","key":"5275_CR16","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aag1166","volume":"9","author":"C Finan","year":"2017","unstructured":"Finan C, Gaulton A, Kruger FA et al (2017) The druggable genome and support for target identification and validation in drug development. Sci Transl Med 9(383):eaag1166. https:\/\/doi.org\/10.1126\/scitranslmed.aag1166","journal-title":"Sci Transl Med"},{"issue":"6","key":"5275_CR17","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.devcel.2014.01.022","volume":"28","author":"I Franco","year":"2014","unstructured":"Franco I, Gulluni F, Campa CC et al (2014) PI3K class II \u03b1 controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function. Dev Cell 28(6):647\u2013658. https:\/\/doi.org\/10.1016\/j.devcel.2014.01.022","journal-title":"Dev Cell"},{"key":"5275_CR18","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/bs.apcsb.2019.01.001","volume":"116","author":"N Fuentes","year":"2019","unstructured":"Fuentes N, Silveyra P (2019) Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol 116:135\u2013170. https:\/\/doi.org\/10.1016\/bs.apcsb.2019.01.001","journal-title":"Adv Protein Chem Struct Biol"},{"issue":"4","key":"5275_CR19","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41591-021-01310-z","volume":"27","author":"L Gaziano","year":"2021","unstructured":"Gaziano L, Giambartolomei C, Pereira AC et al (2021) Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19. Nat Med 27(4):668\u2013676. https:\/\/doi.org\/10.1038\/s41591-021-01310-z","journal-title":"Nat Med"},{"issue":"5","key":"5275_CR20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383","volume":"10","author":"C Giambartolomei","year":"2014","unstructured":"Giambartolomei C, Vukcevic D, Schadt EE et al (2014) Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet 10(5):e1004383. https:\/\/doi.org\/10.1371\/journal.pgen.1004383","journal-title":"PLoS Genet"},{"key":"5275_CR21","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1214","volume":"3","author":"AO Goodman","year":"2011","unstructured":"Goodman AO, Barker RA (2011) Body composition in premanifest Huntington\u2019s disease reveals lower bone density compared to controls. PLoS Curr 3:RRN1214. https:\/\/doi.org\/10.1371\/currents.RRN1214","journal-title":"PLoS Curr"},{"issue":"21","key":"5275_CR22","doi-asserted-by":"publisher","first-page":"2926","DOI":"10.1002\/sim.6522","volume":"34","author":"MFD Greco","year":"2015","unstructured":"Greco MFD, Minelli C, Sheehan NA, Thompson JR (2015) Detecting Pleiotropy in Med 34(21):2926\u20132940. https:\/\/doi.org\/10.1002\/sim.6522","journal-title":"Detecting Pleiotropy in Med"},{"issue":"4","key":"5275_CR23","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1055\/s-0044-1787545","volume":"44","author":"K Griffin","year":"2024","unstructured":"Griffin K, Stitt D (2024) Opioid-associated nervous system injuries. Semin Neurol 44(4):452\u2013458. https:\/\/doi.org\/10.1055\/s-0044-1787545","journal-title":"Semin Neurol"},{"issue":"4","key":"5275_CR24","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.ccell.2017.09.002","volume":"32","author":"F Gulluni","year":"2017","unstructured":"Gulluni F, Martini M, De Santis MC et al (2017) Mitotic spindle assembly and genomic stability in breast cancer require PI3K-C2 \u03b1 scaffolding function. Cancer Cell 32(4):444-459.e7. https:\/\/doi.org\/10.1016\/j.ccell.2017.09.002","journal-title":"Cancer Cell"},{"issue":"4","key":"5275_CR25","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.tcb.2019.01.001","volume":"29","author":"F Gulluni","year":"2019","unstructured":"Gulluni F, De Santis MC, Margaria JP, Martini M, Hirsch E (2019) Class II PI3K functions in cell biology and disease. Trends Cell Biol 29(4):339\u2013359. https:\/\/doi.org\/10.1016\/j.tcb.2019.01.001","journal-title":"Trends Cell Biol"},{"issue":"5","key":"5275_CR26","doi-asserted-by":"publisher","first-page":"821","DOI":"10.18433\/j3vw2f","volume":"16","author":"S Harirforoosh","year":"2013","unstructured":"Harirforoosh S, Asghar W, Jamali F (2013) Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci 16(5):821\u2013847. https:\/\/doi.org\/10.18433\/j3vw2f","journal-title":"J Pharm Pharm Sci"},{"issue":"11","key":"5275_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081","volume":"13","author":"G Hemani","year":"2017","unstructured":"Hemani G, Tilling K, Davey Smith G (2017) Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genet 13(11):e1007081. https:\/\/doi.org\/10.1371\/journal.pgen.1007081","journal-title":"PLoS Genet"},{"issue":"1","key":"5275_CR28","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1253\/circj.cj-12-1573","volume":"78","author":"A Hirayama","year":"2014","unstructured":"Hirayama A, Tanahashi N, Daida H et al (2014) Assessing the cardiovascular riskbetween celecoxib and nonselective nonsteroidal antiinflammatory drugs in patients with rheumatoid arthritis and osteoarthritis. Circ J 78(1):194\u2013205. https:\/\/doi.org\/10.1253\/circj.cj-12-1573","journal-title":"Circ J"},{"issue":"2","key":"5275_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27020785","volume":"27","author":"Z Huang","year":"2026","unstructured":"Huang Z, Wu Y, Li Y (2026) Bone metastasis in estrogen receptor-positive breast cancer: molecular insights and therapeutic advances. Int J Mol Sci 27(2):785. https:\/\/doi.org\/10.3390\/ijms27020785","journal-title":"Int J Mol Sci"},{"key":"5275_CR30","doi-asserted-by":"publisher","unstructured":"Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium, Swerdlow DI, Holmes MV, et al (2012) The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.Lancet.379(9822):1214\u20131224 https:\/\/doi.org\/10.1016\/S0140-6736(12)60110-X","DOI":"10.1016\/S0140-6736(12)60110-X"},{"issue":"42","key":"5275_CR31","doi-asserted-by":"publisher","first-page":"30647","DOI":"10.1039\/d4ra04686b","volume":"14","author":"NA Khalil","year":"2024","unstructured":"Khalil NA, Ahmed EM, Tharwat T, Mahmoud Z (2024) Nsaids between past and present; a long journey towards an ideal COX-2 inhibitor lead. RSC Adv 14(42):30647\u201330661. https:\/\/doi.org\/10.1039\/d4ra04686b","journal-title":"RSC Adv"},{"issue":"24","key":"5275_CR32","doi-asserted-by":"publisher","first-page":"4240","DOI":"10.1242\/jcs.071712","volume":"123","author":"C Krag","year":"2010","unstructured":"Krag C, Malmberg EK, Salcini AE (2010) PI3KC2 \u03b1, a class II PI3K, is required for dynamin-independent internalization pathways. J Cell Sci 123(24):4240\u20134250. https:\/\/doi.org\/10.1242\/jcs.071712","journal-title":"J Cell Sci"},{"issue":"9","key":"5275_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8091306","volume":"8","author":"I Krela-Kazmierczak","year":"2019","unstructured":"Krela-Kazmierczak I, Skrzypczak-Zieli\u0144ska M, Kaczmarek-Ry\u015b M et al (2019) ESR1 gene variants are predictive of osteoporosis in female patients with Crohn\u2019s disease. J Clin Med 8(9):1306. https:\/\/doi.org\/10.3390\/jcm8091306","journal-title":"J Clin Med"},{"issue":"6","key":"5275_CR34","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1096\/fj.09-148072","volume":"24","author":"B Leibiger","year":"2010","unstructured":"Leibiger B, Moede T, Uhles S et al (2010) Insulin-feedback via PI3K-C2alpha activated PKBalpha\/Akt1 is required for glucose-stimulated insulin secretion. FASEB J 24(6):1824\u20131837. https:\/\/doi.org\/10.1096\/fj.09-148072","journal-title":"FASEB J"},{"issue":"1","key":"5275_CR35","doi-asserted-by":"publisher","first-page":"T87","DOI":"10.1530\/JME-17-0284","volume":"61","author":"RC Lindsey","year":"2018","unstructured":"Lindsey RC, Rundle CH, Mohan S (2018) Role of IGF1 and EFN-EPH signaling in skeletal metabolism. J Mol Endocrinol 61(1):T87\u2013T102. https:\/\/doi.org\/10.1530\/JME-17-0284","journal-title":"J Mol Endocrinol"},{"issue":"1","key":"5275_CR36","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1677\/joe.1.06058","volume":"185","author":"P Mendez","year":"2005","unstructured":"Mendez P, Azcoitia I, Garcia-Segura LM (2005) Interdependence of oestrogen and insulin-like growth factor-I in the brain: potential for analysing neuroprotective mechanisms. J Endocrinol 185(1):11\u201317. https:\/\/doi.org\/10.1677\/joe.1.06058","journal-title":"J Endocrinol"},{"issue":"1","key":"5275_CR37","doi-asserted-by":"publisher","DOI":"10.1080\/21675511.2015.1058464","volume":"3","author":"M Mielcarek","year":"2015","unstructured":"Mielcarek M (2015) Huntington\u2019s disease is a multi-system disorder. Rare Dis 3(1):e1058464. https:\/\/doi.org\/10.1080\/21675511.2015.1058464","journal-title":"Rare Dis"},{"issue":"1","key":"5275_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7535","volume":"6","author":"JK Mountford","year":"2015","unstructured":"Mountford JK, Petitjean C, Putra HW et al (2015) The class II PI 3-kinase, PI3KC2 \u03b1, links platelet internal membrane structure to shear-dependent adhesive function. Nat Commun 6(1):6535. https:\/\/doi.org\/10.1038\/ncomms7535","journal-title":"Nat Commun"},{"key":"5275_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2022.113598","volume":"172","author":"NK Panchal","year":"2023","unstructured":"Panchal NK, Prince Sabina E (2023) Non-steroidal anti-inflammatory drugs (NSAIDs): a current insight into its molecular mechanism eliciting organ toxicities. Food Chem Toxicol 172:113598. https:\/\/doi.org\/10.1016\/j.fct.2022.113598","journal-title":"Food Chem Toxicol"},{"issue":"1","key":"5275_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84724-6","volume":"11","author":"CS Parenteau","year":"2021","unstructured":"Parenteau CS, Lau EC, Campbell IC, Courtney A (2021) Prevalence of spine degeneration diagnosis by type, age, gender, and obesity using Medicare data. Sci Rep 11(1):5389. https:\/\/doi.org\/10.1038\/s41598-021-84724-6","journal-title":"Sci Rep"},{"issue":"10","key":"5275_CR41","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1093\/hmg\/8.10.1913","volume":"8","author":"L Peltonen","year":"1999","unstructured":"Peltonen L, Jalanko A, Varilo T (1999) Molecular genetics of the Finnish disease heritage. Hum Mol Genet 8(10):1913\u20131923. https:\/\/doi.org\/10.1093\/hmg\/8.10.1913","journal-title":"Hum Mol Genet"},{"issue":"15","key":"5275_CR42","doi-asserted-by":"publisher","DOI":"10.3390\/nu14153209","volume":"14","author":"L Pelusi","year":"2022","unstructured":"Pelusi L, Mandatori D, Di Pietrantonio N et al (2022) Estrogen receptor 1 (ESR1) and the Wnt\/\u03b2-catenin pathway mediate the effect of the coumarin derivative umbelliferon on bone mineralization. Nutrients 14(15):3209. https:\/\/doi.org\/10.3390\/nu14153209","journal-title":"Nutrients"},{"issue":"7457","key":"5275_CR43","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nature12360","volume":"499","author":"Y Posor","year":"2013","unstructured":"Posor Y, Eichhorn-Gruenig M, Puchkov D et al (2013) Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate. Nature 499(7457):233\u2013237. https:\/\/doi.org\/10.1038\/nature12360","journal-title":"Nature"},{"issue":"4","key":"5275_CR44","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.jocd.2022.08.007","volume":"25","author":"H Ren","year":"2022","unstructured":"Ren H, Liu H, Huang L, Xie W, Lin D, Luo D (2022) Association of ESR1 and ESR2 polymorphisms with osteoporosis: a meta-analysis from 36 studies. J Clin Densitom 25(4):699\u2013711. https:\/\/doi.org\/10.1016\/j.jocd.2022.08.007","journal-title":"J Clin Densitom"},{"issue":"10","key":"5275_CR45","doi-asserted-by":"publisher","first-page":"3705","DOI":"10.1523\/JNEUROSCI.20-10-03705.2000","volume":"20","author":"D Rigamonti","year":"2000","unstructured":"Rigamonti D, Bauer JH, De-Fraja C et al (2000) Wild-type huntingtin protects from apoptosis upstream of caspase-3. J Neurosci 20(10):3705\u20133713. https:\/\/doi.org\/10.1523\/JNEUROSCI.20-10-03705.2000","journal-title":"J Neurosci"},{"key":"5275_CR46","doi-asserted-by":"publisher","unstructured":"Schmidt AF, Finan C, Gordillo-Mara\u00f16n M et al (2020) Genetic drug target validation using Mendelian randomisation. Nat Commun 11(1):3255. https:\/\/doi.org\/10.1038\/s41467-020-16969-0","DOI":"10.1038\/s41467-020-16969-0"},{"issue":"3","key":"5275_CR47","doi-asserted-by":"publisher","first-page":"227","DOI":"10.3233\/JHD-220543","volume":"11","author":"M Seefelder","year":"2022","unstructured":"Seefelder M, Klein FAC, Landwehrmeyer B, Fern\u00e1ndez-Busnadiego R, Kochanek S (2022) Huntingtin and its partner Huntingtin-Associated Protein 40: structural and functional considerations in health and disease. J Huntingtons Dis 11(3):227\u2013242. https:\/\/doi.org\/10.3233\/JHD-220543","journal-title":"J Huntingtons Dis"},{"issue":"2","key":"5275_CR48","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.bpg.2009.11.005","volume":"24","author":"C Sostres","year":"2010","unstructured":"Sostres C, Gargallo CJ, Arroyo MT, Lanas A (2010) Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol 24(2):121\u2013132. https:\/\/doi.org\/10.1016\/j.bpg.2009.11.005","journal-title":"Best Pract Res Clin Gastroenterol"},{"issue":"1","key":"5275_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26280-1","volume":"12","author":"CS Storm","year":"2021","unstructured":"Storm CS, Kia DA, Almramhi MM et al (2021) Finding genetically-supported drug targets for Parkinson\u2019s disease using Mendelian randomization of the druggable genome. Nat Commun 12(1):7342. https:\/\/doi.org\/10.1038\/s41467-021-26280-1","journal-title":"Nat Commun"},{"issue":"2","key":"5275_CR50","doi-asserted-by":"publisher","first-page":"131","DOI":"10.7861\/clinmed.2021-0039","volume":"21","author":"FWD Tai","year":"2021","unstructured":"Tai FWD, McAlindon ME (2021) Non-steroidal anti-inflammatory drugs and the gastrointestinal tract. Clin Med (Lond) 21(2):131\u2013134. https:\/\/doi.org\/10.7861\/clinmed.2021-0039","journal-title":"Clin Med (Lond)"},{"issue":"4","key":"5275_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008088","volume":"15","author":"D Tiosano","year":"2019","unstructured":"Tiosano D, Baris HN, Chen A et al (2019) Mutations in PIK3C2A cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction. PLoS Genet 15(4):e1008088. https:\/\/doi.org\/10.1371\/journal.pgen.1008088","journal-title":"PLoS Genet"},{"issue":"9","key":"5275_CR52","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/s41588-021-00913-z","volume":"53","author":"U V\u00f5sa","year":"2021","unstructured":"V\u00f5sa U, Claringbould A, Westra HJ et al (2021) Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat Genet 53(9):1300\u20131310. https:\/\/doi.org\/10.1038\/s41588-021-00913-z","journal-title":"Nat Genet"},{"issue":"2","key":"5275_CR53","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.yexcr.2016.05.011","volume":"345","author":"B Wang","year":"2016","unstructured":"Wang B, Wang D, Yan T, Yuan H (2016) MiR-138-5p promotes TNF- \u03b1-induced apoptosis in human intervertebral disc degeneration by targeting SIRT1 through PTEN\/PI3K\/Akt signaling. Exp Cell Res 345(2):199\u2013205. https:\/\/doi.org\/10.1016\/j.yexcr.2016.05.011","journal-title":"Exp Cell Res"},{"issue":"10","key":"5275_CR54","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1038\/nm.2928","volume":"18","author":"K Yoshioka","year":"2012","unstructured":"Yoshioka K, Yoshida K, Cui H et al (2012) Endothelial PI3K-C2 \u03b1, a class II PI3K, has an essential role in angiogenesis and vascular barrier function. Nat Med 18(10):1560\u20131569. https:\/\/doi.org\/10.1038\/nm.2928","journal-title":"Nat Med"},{"key":"5275_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104859","volume":"98","author":"N Zhang","year":"2023","unstructured":"Zhang N, Li Y, Sundquist J, Sundquist K, Ji J (2023) Identifying actionable druggable targets for breast cancer: mendelian randomization and population-based analyses. EBioMedicine 98:104859. https:\/\/doi.org\/10.1016\/j.ebiom.2023.104859","journal-title":"EBioMedicine"},{"issue":"5","key":"5275_CR56","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ng.3538","volume":"48","author":"Z Zhu","year":"2016","unstructured":"Zhu Z, Zhang F, Hu H et al (2016) Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat Genet 48(5):481\u2013487. https:\/\/doi.org\/10.1038\/ng.3538","journal-title":"Nat Genet"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05275-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-026-05275-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05275-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T01:44:16Z","timestamp":1783907056000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-026-05275-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":56,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["5275"],"URL":"https:\/\/doi.org\/10.1007\/s00210-026-05275-z","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]},"assertion":[{"value":"14 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval is presented in the mentioned GWAS studies.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for participate"}},{"value":"The authors have given consent for publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial number"}}]}}