{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T13:36:05Z","timestamp":1771076165648,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anorexia nervosa (AN) is a severe psychiatric disorder characterized by substantial heritability and a high mortality rate among psychiatric disorders. While cerebrospinal fluid (CSF) metabolomics has emerged as a novel approach to investigating central nervous system pathologies, its specific causal relationship with anorexia nervosa remains to be fully elucidated. Using genome-wide association study (GWAS) summary statistics for human CSF metabolites and AN information from publicly available datasets, we performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW) method as the primary approach, complemented by sensitivity analyses. Through a comprehensive analysis of 338 CSF metabolites, we identified six metabolites with significant causal relationships with AN risk. 1-stearoyl-2-linoleoyl-gpc (18:0\/18:2) (OR = 1.09, 95% CI 1.00\u20131.18) and alpha-tocopherol (OR = 1.36, 95% CI 1.00\u20131.83) showed positive associations, increasing AN risk. Conversely, sphingomyelin (d18:1\/20:0, d16:1\/22:0) (OR = 0.86, 95% CI 0.77\u20130.95), 2,3-dihydroxy-2-methylbutyrate (OR = 0.92, 95% CI 0.86\u20130.98), N-acetylhistidine (OR = 0.92, 95% CI 0.86\u20130.98), and oxalate (ethanedioate) (OR = 0.83, 95% CI 0.73\u20130.94) had protective effects, reducing AN risk. Sensitivity analyses showed no evidence of horizontal pleiotropy or heterogeneity in the MR results. An MR directionality test and a Steiger filtering test confirmed the absence of reverse causality, thereby substantiating the robustness of our findings. These findings suggest that these CSF metabolites could serve as potential biomarkers for early AN detection and highlight novel therapeutic targets, potentially improving diagnosis and intervention strategies for this challenging disorder.<\/jats:p>","DOI":"10.3390\/ijms26073248","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T07:00:45Z","timestamp":1743490845000},"page":"3248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Six Cerebrospinal Fluid Metabolites Causally Associated with Anorexia Nervosa Risk: A Mendelian Randomization Analysis"],"prefix":"10.3390","volume":"26","author":[{"given":"Cheng-Liang","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu-Wu","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Hong","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1192\/bjp.2019.113","article-title":"Anorexia nervosa: 30-year outcome","volume":"216","author":"Dobrescu","year":"2020","journal-title":"Br. J. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1176\/appi.ajp.157.3.393","article-title":"Controlled family study of anorexia nervosa and bulimia nervosa: Evidence of shared liability and transmission of partial syndromes","volume":"157","author":"Strober","year":"2000","journal-title":"Am. J. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1001\/archpsyc.63.3.305","article-title":"Prevalence, heritability, and prospective risk factors for anorexia nervosa","volume":"63","author":"Bulik","year":"2006","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.biopsych.2006.03.040","article-title":"The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication","volume":"61","author":"Hudson","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1038\/s41588-019-0439-2","article-title":"Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa","volume":"51","author":"Watson","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1177\/0148607188012002212","article-title":"Role of biochemical mediators in clinical nutrition and surgical metabolism","volume":"12","author":"Pomposelli","year":"1988","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jad.2024.09.115","article-title":"Causal effects of gut microbiota, metabolites, immune cells, liposomes, and inflammatory proteins on anorexia nervosa: A mediation joint multi-omics Mendelian randomization analysis","volume":"368","author":"Li","year":"2025","journal-title":"J. Affect. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1017\/S0033291712002620","article-title":"Update on the treatment of anorexia nervosa: Review of clinical trials, practice guidelines and emerging interventions","volume":"43","author":"Watson","year":"2013","journal-title":"Psychol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/eat.22293","article-title":"A nation-wide study of the family aggregation and risk factors in anorexia nervosa over three generations","volume":"48","author":"Steinhausen","year":"2015","journal-title":"Int. J. Eat. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wong, T.H.T., Mo, J.M.Y., Zhou, M., Zhao, J.V., Schooling, C.M., He, B., Luo, S., and Au Yeung, S.L. (2024). A two-sample Mendelian randomization study explores metabolic profiling of different glycemic traits. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-05977-1"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lin, L., Tang, Y., Ning, K., Li, X., and Hu, X. (2024). Investigating the causal associations between metabolic biomarkers and the risk of kidney cancer. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06114-8"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrm.2016.25","article-title":"Metabolomics: Beyond biomarkers and towards mechanisms","volume":"17","author":"Johnson","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/schbul\/sbac130","article-title":"Association Between Human Blood Metabolome and the Risk of Psychiatric Disorders","volume":"49","author":"Jia","year":"2023","journal-title":"Schizophr. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Freuer, D., and Meisinger, C. (2024). Mediation-adjusted multivariable Mendelian randomisation study identified novel metabolites related to mental health. BMJ Ment. Health, 27.","DOI":"10.1136\/bmjment-2024-301230"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tezenas du Montcel, C., Duriez, P., Cao, J., Lebrun, N., Ramoz, N., Viltart, O., Gorwood, P., and Tolle, V. (2023). The role of dysregulated ghrelin\/LEAP-2 balance in anorexia nervosa. iScience, 26.","DOI":"10.1016\/j.isci.2023.107996"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bao, H., Chen, Y., Meng, Z., and Chu, Z. (2024). The causal relationship between CSF metabolites and GBM: A two-sample mendelian randomization analysis. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12901-7"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mravinacov\u00e1, S., Alanko, V., Bergstr\u00f6m, S., Bridel, C., Pijnenburg, Y., Hagman, G., Kivipelto, M., Teunissen, C., Nilsson, P., and Matton, A. (2024). CSF protein ratios with enhanced potential to reflect Alzheimer\u2019s disease pathology and neurodegeneration. Mol. Neurodegener., 19.","DOI":"10.1186\/s13024-024-00705-z"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/BF00339562","article-title":"Reversible and non-reversible enlargement of cerebrospinal fluid spaces in anorexia nervosa","volume":"27","author":"Artmann","year":"1985","journal-title":"Neuroradiology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Curzio, O., Calderoni, S., Maestro, S., Rossi, G., De Pasquale, C.F., Belmonti, V., Apicella, F., Muratori, F., and Retico, A. (2020). Lower gray matter volumes of frontal lobes and insula in adolescents with anorexia nervosa restricting type: Findings from a Brain Morphometry Study. Eur. Psychiatry, 63.","DOI":"10.1192\/j.eurpsy.2020.19"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/epi4.13101","article-title":"Cerebrospinal fluid metabolites as potential biomarkers for epilepsy: Insights from genome-wide association studies","volume":"10","author":"Zhao","year":"2024","journal-title":"Epilepsia Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dong, R., Lu, Q., Kang, H., Suridjan, I., Kollmorgen, G., Wild, N., Deming, Y., Van Hulle, C.A., Anderson, R.M., and Zetterberg, H. (2023). CSF metabolites associated with biomarkers of Alzheimer\u2019s disease pathology. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1214932"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jie, J., Gong, Y., Hu, H., and Liu, S. (2024). The role of cerebrospinal fluid metabolites in mediating the impact of lipids on Late-Onset Alzheimer\u2019s Disease: A two-step mendelian randomization analysis. J. Transl. Med., 22.","DOI":"10.1186\/s12967-024-05796-2"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhang, J., Zhang, X., Xiao, B., Ouyang, J., Wang, P., and Peng, X. (2024). Mendelian randomization study of causal link from Cerebrospinal fluid metabolomics to neurodegenerative diseases. Neurogenetics, 26.","DOI":"10.1007\/s10048-024-00792-6"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian Randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/sim.3034","article-title":"Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: Genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Hemani","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sheehan, N.A., Didelez, V., Burton, P.R., and Tobin, M.D. (2008). Mendelian randomisation and causal inference in observational epidemiology. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050177"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17221","DOI":"10.1074\/jbc.R000005200","article-title":"Structure and function of sphingolipid- and cholesterol-rich membrane rafts","volume":"275","author":"Brown","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_30","unstructured":"Alaaraj, N., Soliman, A., Hamed, N., Alyafei, F., and De Sanctis, V. (2021). Understanding the complex role of mTORC as an intracellular critical mediator of whole-body metabolism in anorexia nervosa: A mini review. Acta Biomed., 92."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.neubiorev.2010.11.001","article-title":"The socio-emotional processing stream in Anorexia Nervosa","volume":"35","author":"Oldershaw","year":"2011","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1053\/scnp.2001.22263","article-title":"Starving the brain: Structural abnormalities and cognitive impairment in adolescents with anorexia nervosa","volume":"6","author":"Katzman","year":"2001","journal-title":"Semin. Clin. Neuropsychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrn2682","article-title":"New insights into symptoms and neurocircuit function of anorexia nervosa","volume":"10","author":"Kaye","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1176\/appi.ajp.161.7.1238","article-title":"Medial prefrontal cortex activity associated with symptom provocation in eating disorders","volume":"161","author":"Uher","year":"2004","journal-title":"Am. J. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.pscychresns.2005.08.002","article-title":"Comparison of regional cerebral blood flow in patients with anorexia nervosa before and after weight gain","volume":"140","author":"Kojima","year":"2005","journal-title":"Psychiatry Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kabir, F., Atkinson, R., Cook, A.L., Phipps, A.J., and King, A.E. (2022). The role of altered protein acetylation in neurodegenerative disease. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.1025473"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.3945\/jn.114.196105","article-title":"Insufficient intake of L-histidine reduces brain histamine and causes anxiety-like behaviors in male mice","volume":"144","author":"Yoshikawa","year":"2014","journal-title":"J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41581-022-00643-3","article-title":"Oxalate homeostasis","volume":"19","author":"Ermer","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1053\/j.ajkd.2012.03.019","article-title":"Anorexia nervosa and the kidney","volume":"60","author":"Bouquegneau","year":"2012","journal-title":"Am. J. Kidney Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1681\/ASN.2007030261","article-title":"Hypokalemic nephropathy is associated with impaired angiogenesis","volume":"19","author":"Reungjui","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"478","DOI":"10.2169\/internalmedicine.31.478","article-title":"A case of anorexia nervosa with acute renal failure induced by rhabdomyolysis; possible involvement of hypophosphatemia or phosphate depletion","volume":"31","author":"Wada","year":"1992","journal-title":"Intern. Med."},{"key":"ref_42","first-page":"453","article-title":"Renal dysfunction in patients with eating disorders","volume":"56","author":"Sonoda","year":"2016","journal-title":"Jpn. J. Psychosom. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1017\/S0033291796004394","article-title":"Medical findings and predictors of long-term physical outcome in anorexia nervosa: A prospective, 12-year follow-up study","volume":"27","author":"Herzog","year":"1997","journal-title":"Psychol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2215\/CJN.08600520","article-title":"NAT8 Variants, N-Acetylated Amino Acids, and Progression of CKD","volume":"16","author":"Luo","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0197-0070(84)80245-4","article-title":"Anorexia nervosa and nephrolithiasis","volume":"5","author":"Silber","year":"1984","journal-title":"J. Adolesc. Health Care"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3233\/JAD-200535","article-title":"Potentially Pathogenic Calcium Oxalate Dihydrate and Titanium Dioxide Crystals in the Alzheimer\u2019s Disease Entorhinal Cortex","volume":"77","author":"Heller","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Yap, H.-M., and Lye, K.-L. (2020). An insight of vitamin E as neuroprotective agents. Prog. Microbes Mol. Biol., 3.","DOI":"10.36877\/pmmb.a0000071"},{"key":"ref_48","first-page":"585","article-title":"Tocopherols and tocotrienols as vitamin E","volume":"68","author":"Nowak","year":"2014","journal-title":"Chemik"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"807","DOI":"10.2165\/00023210-200418120-00005","article-title":"Tocopherol (vitamin E) in Alzheimer\u2019s disease and other neurodegenerative disorders","volume":"18","author":"Berman","year":"2004","journal-title":"CNS Drugs"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Azzi, A. (2019). Tocopherols, tocotrienols and tocomonoenols: Many similar molecules but only one vitamin E. Redox Biol., 26.","DOI":"10.1016\/j.redox.2019.101259"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1007\/BF03325347","article-title":"Tumour necrosis factor alpha and oxidative stress as maintaining factors in the evolution of anorexia nervosa","volume":"17","author":"Agnello","year":"2012","journal-title":"Eat. Weight Disord."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.chembiol.2020.03.013","article-title":"The Chemistry and Biology of Ferroptosis","volume":"27","author":"Stockwell","year":"2020","journal-title":"Cell Chem. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Costa, I., Barbosa, D.J., Benfeito, S., Silva, V., Chavarria, D., Borges, F., Remi\u00e3o, F., and Silva, R. (2023). Molecular mechanisms of ferroptosis and their involvement in brain diseases. Pharmacol. Ther., 244.","DOI":"10.1016\/j.pharmthera.2023.108373"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"La Torre, M.E., Villano, I., Monda, M., Messina, A., Cibelli, G., Valenzano, A., Pisanelli, D., Panaro, M.A., Tartaglia, N., and Ambrosi, A. (2021). Role of Vitamin E and the Orexin System in Neuroprotection. Brain Sci., 11.","DOI":"10.3390\/brainsci11081098"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"602","DOI":"10.4103\/1735-5362.301345","article-title":"Evaluation of neuroprotective effects of alpha-tocopherol in cuprizone-induced demyelination model of multiple sclerosis","volume":"15","author":"Mitra","year":"2020","journal-title":"Res. Pharm. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ambrogini, P., Betti, M., Galati, C., Di Palma, M., Lattanzi, D., Savelli, D., Galli, F., Cuppini, R., and Minelli, A. (2016). \u03b1-Tocopherol and Hippocampal Neural Plasticity in Physiological and Pathological Conditions. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122107"},{"key":"ref_57","first-page":"873","article-title":"Vitamin A metabolism in plasma of normal and anorectic women","volume":"46","author":"Vaisman","year":"1992","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1002\/ajmg.a.38658","article-title":"Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency","volume":"176","author":"Fitzsimons","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3949\/ccjm.87a.19084","article-title":"Medical complications of anorexia nervosa","volume":"87","author":"Cost","year":"2020","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1161\/HYPERTENSIONAHA.124.22999","article-title":"Novel Metabolites Associated With Blood Pressure After Dietary Interventions","volume":"81","author":"Sun","year":"2024","journal-title":"Hypertension"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.clinthera.2020.11.006","article-title":"Current Therapeutic Approaches to Anorexia Nervosa: State of the Art","volume":"43","author":"Muratore","year":"2021","journal-title":"Clin. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pournajaf, S., Dargahi, L., Javan, M., and Pourgholami, M.H. (2022). Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.807639"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1681\/ASN.2016010098","article-title":"Mendelian Randomization as an Approach to Assess Causality Using Observational Data","volume":"27","author":"Sekula","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Au Yeung, S.L., and Gill, D. (2023). Standardizing the reporting of Mendelian randomization studies. BMC Med., 21.","DOI":"10.1186\/s12916-023-02894-8"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Panyard, D.J., Kim, K.M., Darst, B.F., Deming, Y.K., Zhong, X., Wu, Y., Kang, H., Carlsson, C.M., Johnson, S.C., and Asthana, S. (2021). Cerebrospinal fluid metabolomics identifies 19 brain-related phenotype associations. Commun. Biol., 4.","DOI":"10.1038\/s42003-020-01583-z"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1176\/appi.ajp.2017.16121402","article-title":"Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa","volume":"174","author":"Duncan","year":"2017","journal-title":"Am. J. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1093\/ije\/dyx028","article-title":"Two-sample Mendelian randomization: Avoiding the downsides of a powerful, widely applicable but potentially fallible technique","volume":"45","author":"Hartwig","year":"2016","journal-title":"Int. J. Epidemiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3248\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:07:02Z","timestamp":1760029622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,31]]},"references-count":68,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26073248"],"URL":"https:\/\/doi.org\/10.3390\/ijms26073248","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,31]]}}}