{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:28:25Z","timestamp":1790386105418,"version":"4.1.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Although homocysteine (Hcy) increases the risk of cardiovascular diseases, its effects on obesity and musculoskeletal diseases remain unclear. We performed a Mendelian randomization study to estimate the associations between Hcy and B vitamin concentrations and their effects on obesity and musculoskeletal-relevant diseases in the general population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected independent single nucleotide polymorphisms of Hcy (<jats:italic>n<\/jats:italic> = 44,147), vitamin B12 (<jats:italic>n<\/jats:italic> = 45,576), vitamin B6 (<jats:italic>n<\/jats:italic> = 1864), and folate (<jats:italic>n<\/jats:italic> = 37,465) at the genome-wide significance level as instruments and applied them to the studies of summary-level data for fat and musculoskeletal phenotypes from the UK Biobank study (<jats:italic>n<\/jats:italic> = 331,117), the FinnGen consortium (<jats:italic>n<\/jats:italic> = 218,792), and other consortia. Two-sample Mendelian randomization (MR) approaches were utilized in this study. The inverse variance weighting (IVW) was adopted as the main analysis. MR-PRESSO, MR-Egger, the weighted median estimate, bidirectional MR, and multivariable MR were performed as sensitivity methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher Hcy concentrations were robustly associated with an increased risk of knee osteoarthritis [odds ratio (OR) 1.119; 95% confidence interval (CI) 1.032\u20131.214; <jats:italic>P<\/jats:italic> = 0.007], hospital-diagnosed osteoarthritis (OR 1.178; 95% CI 1.012\u20131.37; <jats:italic>P<\/jats:italic> = 0.034), osteoporosis with pathological fracture (OR 1.597; 95% CI 1.036\u20132.46; <jats:italic>P<\/jats:italic> = 0.034), and soft tissue disorder (OR 1.069; 95% CI 1.001\u20131.141; <jats:italic>P<\/jats:italic> = 0.045) <jats:italic>via<\/jats:italic> an inverse variance weighting method and other MR approaches. Higher vitamin B12 levels were robustly associated with decreased body fat percentage and its subtypes (all <jats:italic>P<\/jats:italic> &amp;lt; 0.05). Bidirectional analyses showed no reverse causation. Multivariable MR analyses and other sensitivity analyses showed directionally similar results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There exist significant causal effects of vitamin B12 in the serum and Hcy in the blood on fat and musculoskeletal diseases, respectively. These findings may have an important insight into the pathogenesis of obesity and musculoskeletal diseases and other possible future therapies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2022.1048122","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T21:47:46Z","timestamp":1669326466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study"],"prefix":"10.3389","volume":"9","author":[{"given":"Liwan","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuquan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Qing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/j.1467-789X.2006.00251.x","article-title":"Musculoskeletal disorders associated with obesity: a biomechanical perspective","volume":"7","author":"Wearing","year":"2006","journal-title":"Obes Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1111\/j.1479-8077.2004.00102.x","article-title":"Musculoskeletal medicine: the challenge of the bone and joint decade","volume":"7","author":"Brooks","year":"2004","journal-title":"APLAR J Rheumatol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3389\/fphys.2018.00112","article-title":"Obesity, metabolic syndrome, and musculoskeletal disease: common inflammatory pathways suggest a central role for loss of muscle integrity","volume":"9","author":"Collins","year":"2018","journal-title":"Front Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1136\/annrheumdis-2018-214200","article-title":"Wnt16 attenuates osteoarthritis progression through a PCP\/JNK-mTORC1-PTHrP cascade","volume":"78","author":"Tong","year":"2019","journal-title":"Ann Rheum Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e2202102","DOI":"10.1002\/advs.202202102","article-title":"Magnesium-encapsulated injectable hydrogel and 3D-engineered polycaprolactone conduit facilitate peripheral nerve regeneration","volume":"9","author":"Yao","year":"2022","journal-title":"Adv Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.numecd.2007.10.002","article-title":"Sarcopenic obesity: a new category of obesity in the elderly","volume":"18","author":"Zamboni","year":"2008","journal-title":"Nutr Metab Cardiovasc Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1111\/j.1749-6632.2000.tb06498.x","article-title":"Body composition in healthy aging","volume":"904","author":"Baumgartner","year":"2000","journal-title":"Ann N Y Acad Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.jpain.2015.04.006","article-title":"Body composition is associated with multisite lower body musculoskeletal pain in a community-based study","volume":"16","author":"Brady","year":"2015","journal-title":"J Pain."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/j.clnu.2016.11.011","article-title":"Determinants of hyperhomocysteinemia in healthy and hypertensive subjects: a population-based study and systematic review","volume":"36","author":"Han","year":"2017","journal-title":"Clin Nutr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12986-017-0233-z","article-title":"The metabolism and significance of homocysteine in nutrition and health","volume":"14","author":"Kumar","year":"2017","journal-title":"Nutr Metab."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1016\/j.clnu.2017.07.005","article-title":"Relevance of plasma levels of free homocysteine and methionine as risk predictors for ischemic stroke in the young","volume":"37","author":"Rudreshkumar","year":"2018","journal-title":"Clin Nutr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1093\/ajcn\/73.3.613","article-title":"Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort","volume":"73","author":"Jacques","year":"2001","journal-title":"Am J Clin Nutr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.nutres.2017.10.008","article-title":"Total homocysteine is positively correlated with body mass index, waist-to-hip ratio, and fat mass among overweight reproductive women: a cross-sectional study","volume":"48","author":"Al-Bayyari","year":"2017","journal-title":"Nutr Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.2147\/dmso.s205379","article-title":"Plausible relationship between homocysteine and obesity risk via MTHFR gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization","volume":"12","author":"Fu","year":"2019","journal-title":"Diabetes Metab Syndr Obes."},{"key":"B15","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.gde.2005.08.002","article-title":"DNA methylation and histone modifications: teaming up to silence genes","volume":"15","author":"Fuks","year":"2005","journal-title":"Curr Opin Genet Dev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/bf03350812","article-title":"Are genetic variants of the methyl group metabolism enzymes risk factors predisposing to obesity?","volume":"30","author":"Terruzzi","year":"2007","journal-title":"J Endocrinol Invest."},{"key":"B17","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1093\/jn\/137.2.311","article-title":"New insights into the regulation of methyl group and homocysteine metabolism","volume":"137","author":"Williams","year":"2007","journal-title":"J Nutr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1152\/physrev.00003.2018","article-title":"Homocysteine modification in protein structure\/function and human disease","volume":"99","author":"Jakubowski","year":"2019","journal-title":"Physiol Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/0925-4439(95)00119-0","article-title":"Evidence for McKusick's hypothesis of deficient collagen cross-linking in patients with homocystinuria","volume":"1315","author":"Lubec","year":"1996","journal-title":"Biochim Biophys Acta."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1002\/jor.21415","article-title":"Homocysteine mediated decrease in bone blood flow and remodeling: role of folic acid","volume":"29","author":"Tyagi","year":"2011","journal-title":"J Orthop Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1016\/j.clnu.2021.02.045","article-title":"Causal effects of homocysteine levels on the changes of bone mineral density and risk for bone fracture: a two-sample mendelian randomization study","volume":"40","author":"Wang","year":"2021","journal-title":"Clin Nutr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1359\/jbmr.0301261","article-title":"Association of a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with bone phenotypes depends on plasma folate status","volume":"19","author":"McLean","year":"2004","journal-title":"J Bone Miner Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1096\/fj.08-120584","article-title":"Mouse models of cystathionine beta-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia","volume":"23","author":"Gupta","year":"2009","journal-title":"FASEB J."},{"key":"B24","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1136\/bmj.316.7135.894","article-title":"Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration","volume":"316","author":"Collaboration","year":"1998","journal-title":"BMJ"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1001\/jama.293.9.1082","article-title":"Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial","volume":"293","author":"Sato","year":"2005","journal-title":"JAMA."},{"key":"B26","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1093\/ajcn\/88.3.738","article-title":"Homocysteine, cysteine, and body composition in the Hordaland Homocysteine Study: does cysteine link amino acid and lipid metabolism?","volume":"88","author":"Elshorbagy","year":"2008","journal-title":"Am J Clin Nutr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s00296-008-0693-6","article-title":"Strontium ranelate decreases plasma homocysteine levels in postmenopausal osteoporotic women","volume":"29","author":"Bayhan","year":"2009","journal-title":"Rheumatol Int."},{"key":"B28","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/s00394-010-0165-0","article-title":"Relation of body mass index to blood folate and total homocysteine concentrations in Japanese adults","volume":"50","author":"Nakazato","year":"2011","journal-title":"Eur J Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1007\/s00404-011-2079-3","article-title":"Bone mineral density is not associated with homocysteine level, folate and vitamin B12 status","volume":"285","author":"Rumbak","year":"2012","journal-title":"Arch Gynecol Obstet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"129","DOI":"10.11005\/jbm.2016.23.3.129","article-title":"Association between Homocysteine and Bone Mineral Density according to Age and Sex in Healthy Adults","volume":"23","author":"Kim","year":"2016","journal-title":"J Bone Metab."},{"key":"B31","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s10654-016-0215-x","article-title":"Genetic determinants of serum vitamin B12 and their relation to body mass index","volume":"32","author":"Allin","year":"2017","journal-title":"Eur J Epidemiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"9276097","DOI":"10.1155\/2019\/9276097","article-title":"Hyperhomocysteinemia associated with low muscle mass, muscle function in elderly hemodialysis patients: an analysis of multiple dialysis centers","volume":"2019","author":"Wang","year":"2019","journal-title":"Biomed Res Int."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.3390\/nu11071614","article-title":"Central but not general obesity is positively associated with the risk of hyperhomocysteinemia in middle-aged women","volume":"11","author":"Wang","year":"2019","journal-title":"Nutrients."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1007\/s00394-019-01985-8","article-title":"B-vitamins and body composition: integrating observational and experimental evidence from the B-PROOF study","volume":"59","author":"Oliai Araghi","year":"2020","journal-title":"Eur J Nutr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3648","DOI":"10.3390\/nu13103648","article-title":"Association of obesity with the risk of hyperhomocysteinemia among the Chinese Community residents: a prospective cohort study in < city>Shanghai < \/city>, China","volume":"13","author":"Xiang","year":"2021","journal-title":"Nutrients."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","article-title":"'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?","volume":"32","author":"Smith","year":"2003","journal-title":"Int J Epidemiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1093\/ije\/dyw127","article-title":"Commentary: two-sample Mendelian randomization: opportunities and challenges","volume":"45","author":"Lawlor","year":"2016","journal-title":"Int J Epidemiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"k601","DOI":"10.1136\/bmj.k601","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ."},{"key":"B39","doi-asserted-by":"publisher","first-page":"19009605","DOI":"10.1101\/19009605","article-title":"Exploring and mitigating potential bias when genetic instrumental variables are associated with multiple non-exposure traits in Mendelian randomization","author":"Yang","year":"2019","journal-title":"medRxiv"},{"key":"B40","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1093\/aje\/kwu283","article-title":"Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects","volume":"181","author":"Burgess","year":"2015","journal-title":"Am J Epidemiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e1003530","DOI":"10.1371\/journal.pgen.1003530","article-title":"Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets","volume":"9","author":"Grarup","year":"2013","journal-title":"PLoS Genet."},{"key":"B42","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.ajhg.2009.02.011","article-title":"Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations","volume":"84","author":"Tanaka","year":"2009","journal-title":"Am J Hum Genet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"668","DOI":"10.3945\/ajcn.112.044545","article-title":"Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease","volume":"98","author":"van Meurs","year":"2013","journal-title":"Am J Clin Nutr."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med."},{"key":"B45","unstructured":"2020"},{"key":"B46","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/s41467-017-00108-3","article-title":"Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1\/TOM1L2 locus","volume":"8","author":"Medina-Gomez","year":"2017","journal-title":"Nat Commun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/s41467-017-00031-7","article-title":"Large meta-analysis of genome-wide association studies identifies five loci for lean body mass","volume":"8","author":"Zillikens","year":"2017","journal-title":"Nat Commun."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1038\/s41588-018-0147-3","article-title":"Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 11 million individuals","volume":"50","author":"Lee","year":"2018","journal-title":"Nat Genet."},{"key":"B49","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/s41588-018-0307-5","article-title":"Association studies of up to 12 million individuals yield new insights into the genetic etiology of tobacco and alcohol use","volume":"51","author":"Liu","year":"2019","journal-title":"Nat Genet."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1002\/sim.7221","article-title":"Framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization","volume":"36","author":"Bowden","year":"2017","journal-title":"Stat Med."},{"key":"B51","doi-asserted-by":"publisher","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":"B52","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","article-title":"PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations","volume":"35","author":"Kamat","year":"2019","journal-title":"Bioinformatics."},{"key":"B55","doi-asserted-by":"publisher","first-page":"e002725","DOI":"10.1161\/circgen.119.002725","article-title":"Polygenic hyperlipidemias and coronary artery disease risk","volume":"13","author":"Ripatti","year":"2020","journal-title":"Circ Genom Precis Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1093\/ije\/dyt179","article-title":"Calculating statistical power in Mendelian randomization studies","volume":"42","author":"Brion","year":"2013","journal-title":"Int J Epidemiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1093\/bioinformatics\/btw613","article-title":"LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis","volume":"33","author":"Zheng","year":"2017","journal-title":"Bioinformatics."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1093\/ije\/dyx034","article-title":"MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data","volume":"46","author":"Yavorska","year":"2017","journal-title":"Int J Epidemiol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1002\/oby.22857","article-title":"Causal pathways from body components and regional fat to extensive metabolic phenotypes: a mendelian randomization study","volume":"28","author":"Si","year":"2020","journal-title":"Obesity."},{"key":"B62","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1007\/s00415-020-10119-8","article-title":"An atlas on risk factors for multiple sclerosis: a Mendelian randomization study","volume":"268","author":"Yuan","year":"2021","journal-title":"J Neurol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1001\/jama.1993.03510220049033","article-title":"Vitamin status and intake as primary determinants of homocysteinemia in an elderly population","volume":"270","author":"Selhub","year":"1993","journal-title":"JAMA."},{"key":"B64","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.pcad.2018.07.003","article-title":"An overview and update on obesity and the obesity paradox in cardiovascular diseases","volume":"61","author":"Elagizi","year":"2018","journal-title":"Prog Cardiovasc Dis."},{"key":"B65","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.gene.2018.09.019","article-title":"Gene-gene interactions and associations of six hypertension related single nucleotide polymorphisms with obesity risk in a Chinese children population","volume":"679","author":"Fu","year":"2018","journal-title":"Gene."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1111\/jch.13737","article-title":"Evidence on the causal link between homocysteine and hypertension from a meta-analysis of 40 173 individuals implementing Mendelian randomization","volume":"21","author":"Fu","year":"2019","journal-title":"J Clin Hypertens."},{"key":"B67","doi-asserted-by":"publisher","first-page":"654804","DOI":"10.3389\/fgene.2021.654804","article-title":"A novel approach integrating hierarchical clustering and weighted combination for association study of multiple phenotypes and a genetic variant","volume":"12","author":"Fu","year":"2021","journal-title":"Front Genet."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1016\/j.numecd.2022.03.030","article-title":"Distinct causal effects of body fat distribution on cardiometabolic traits among children: findings from the BCAMS study","volume":"32","author":"Fu","year":"2022","journal-title":"Nutr Metab Cardiovasc Dis."},{"key":"B69","doi-asserted-by":"publisher","first-page":"791920","DOI":"10.3389\/fgene.2022.791920","article-title":"A Novel hierarchical clustering approach for joint analysis of multiple phenotypes uncovers obesity variants based on ARIC","volume":"13","author":"Fu","year":"2022","journal-title":"Front Genet."},{"key":"B70","doi-asserted-by":"publisher","first-page":"e13895","DOI":"10.1111\/eci.13895.","article-title":"Association between homocysteine and nonalcoholic fatty liver disease: Mendelian randomisation study","author":"Fu","year":"2022","journal-title":"Eur J Clin Invest."},{"key":"B71","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1007\/s40471-017-0128-6","article-title":"Recent developments in Mendelian randomization studies","volume":"4","author":"Zheng","year":"2017","journal-title":"Curr Epidemiol Rep."},{"key":"B72","doi-asserted-by":"publisher","first-page":"e1006944","DOI":"10.1371\/journal.pgen.1006944","article-title":"Genetic epidemiology and Mendelian randomization for informing disease therapeutics: conceptual and methodological challenges","volume":"13","author":"Paternoster","year":"2017","journal-title":"PLoS Genet."},{"key":"B73","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.biochi.2020.03.001","article-title":"Body mass index determines the response of plasma sulfur amino acids to methionine loading","volume":"173","author":"Elshorbagy","year":"2020","journal-title":"Biochimie."},{"key":"B74","doi-asserted-by":"publisher","first-page":"E703","DOI":"10.1152\/ajpendo.00050.2011","article-title":"Homocysteine suppresses lipolysis in adipocytes by activating the AMPK pathway","volume":"301","author":"Wang","year":"2011","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"B75","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1097\/MCO.0b013e32834d199f","article-title":"Cysteine and obesity: consistency of the evidence across epidemiologic, animal and cellular studies","volume":"15","author":"Elshorbagy","year":"2012","journal-title":"Curr Opin Clin Nutr Metab Care."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1826780","DOI":"10.1155\/2019\/1826780","article-title":"Hypercysteinemia, a potential risk factor for central obesity and related disorders in Azores, Portugal","volume":"2019","author":"Lima","year":"2019","journal-title":"J Nutr Metab."},{"key":"B77","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.redox.2018.01.010","article-title":"Homocysteine causes dysfunction of chondrocytes and oxidative stress through repression of SIRT1\/AMPK pathway: a possible link between hyperhomocysteinemia and osteoarthritis","volume":"15","author":"Ma","year":"2018","journal-title":"Redox Biol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.amjmed.2014.02.007","article-title":"Muscle mass index as a predictor of longevity in older adults","volume":"127","author":"Srikanthan","year":"2014","journal-title":"Am J Med."},{"key":"B79","doi-asserted-by":"publisher","first-page":"15074","DOI":"10.3390\/ijms140715074","article-title":"Defective homocysteine metabolism: potential implications for skeletal muscle malfunction","volume":"14","author":"Veeranki","year":"2013","journal-title":"Int J Mol Sci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"605","DOI":"10.3945\/jn.114.205203","article-title":"Higher-protein diets are associated with higher HDL cholesterol and lower BMI and waist circumference in US adults","volume":"145","author":"Pasiakos","year":"2015","journal-title":"J Nutr."},{"key":"B81","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.celrep.2017.06.080","article-title":"Loss of hepatic mitochondrial long-chain fatty acid oxidation confers resistance to diet-induced obesity and glucose intolerance","volume":"20","author":"Lee","year":"2017","journal-title":"Cell Rep."},{"key":"B82","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jnutbio.2012.01.004","article-title":"Maternal dietary folate and\/or vitamin B12 restrictions alter body composition (adiposity) and lipid metabolism in Wistar rat offspring","volume":"24","author":"Kumar","year":"2013","journal-title":"J Nutr Biochem."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.3390\/nu12071925","article-title":"Low Vitamin B12 and lipid metabolism: evidence from pre-clinical and clinical studies","volume":"12","author":"Boachie","year":"2020","journal-title":"Nutrients"},{"key":"B84","doi-asserted-by":"publisher","first-page":"19351","DOI":"10.1073\/pnas.0707258104","article-title":"DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status","volume":"104","author":"Sinclair","year":"2007","journal-title":"Proc Natl Acad Sci USA."},{"key":"B85","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1210\/er.2012-1012","article-title":"The roles of vitamin D in skeletal muscle: form, function, and metabolism","volume":"34","author":"Girgis","year":"2013","journal-title":"Endocr Rev."},{"key":"B86","doi-asserted-by":"publisher","first-page":"nu8060319","DOI":"10.3390\/nu8060319","article-title":"Crucial role of vitamin D in the musculoskeletal system","volume":"8","author":"Wintermeyer","year":"2016","journal-title":"Nutrients."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.1048122\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T21:47:52Z","timestamp":1669326472000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.1048122\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":86,"alternative-id":["10.3389\/fnut.2022.1048122"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.1048122","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]},"article-number":"1048122"}}