{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:55:35Z","timestamp":1788782135829,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T00:00:00Z","timestamp":1720742400000},"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. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The relationship between socioeconomic status and frailty has been extensively investigated in the literature, but it remains unclear whether a causal relationship exists. Our goal is to evaluate the causal relationship between six socioeconomic traits and the frailty index using summary-level data for single nucleotide polymorphisms from large genome-wide association studies with individuals of European ancestry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A two-sample MR was performed. We applied the inverse variance weighted (IVW) method for the primary estimate, with sensitivity analyses conducted using alternative MR methods to evaluate the robustness of the findings. A subsequent multivariable MR was undertaken to adjust for the effects of body mass index (BMI). Finally, the MR Steiger directionality test was performed to confirm the causal direction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The IVW MR analysis revealed significant associations between various socioeconomic factors and the frailty index. Specifically, genetically predicated age completed full time education (\u03b2 = \u22120.477, 95% confidence interval [CI]: \u22120.634 to \u22120.319) and average total household income before tax (\u03b2 = \u22120.321, 95% CI: \u22120.410 to \u22120.232) were negatively associated with the frailty index. On the other hand, genetically predicted job involves heavy manual or physical work (\u03b2 = 0.298, 95% CI: 0.113 to 0.484), job involves mainly walking or standing (\u03b2 = 0.179, 95% CI: 0.013 to 0.345), Townsend deprivation index at recruitment (\u03b2 = 0.535, 95% CI: 0.285 to 0.785), and social isolation\/loneliness (\u03b2 = 1.344, 95% CI: 0.834 to 1.853) were positively associated with the frailty index. Sensitivity analysis using other MR methods and multivariable MR analysis adjusting for BMI yielded stable results. The MR Steiger directionality test confirmed the causal direction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings highlight the importance of socioeconomic factors in affecting frailty risk. Future research should focus on unraveling the pathways through which these socioeconomic factors exert their effects on frailty, with the ultimate goal of developing targeted strategies to mitigate the risk of frailty.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1344217","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T04:59:35Z","timestamp":1720760375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Causal effects of socioeconomic traits on frailty: a Mendelian randomization study"],"prefix":"10.3389","volume":"11","author":[{"given":"Jian","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1016\/S0140-6736(19)31785-4","article-title":"Management of frailty: opportunities, challenges, and future directions","volume":"394","author":"Dent","year":"2019","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1093\/ageing\/afu148","article-title":"Prevalence of frailty and disability: findings from the English Longitudinal Study of Ageing","volume":"44","author":"Gale","year":"2015","journal-title":"Age Ageing."},{"key":"B3","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.jamda.2020.12.026","article-title":"Physical frailty, multimorbidity, and all-cause mortality in an older population from Southern Italy: results from the Salus in Apulia study","volume":"22","author":"Castellana","year":"2021","journal-title":"J Am Med Dir Assoc."},{"key":"B4","doi-asserted-by":"publisher","first-page":"879","DOI":"10.3233\/JAD-230312","article-title":"Depressive and biopsychosocial frailty phenotypes: impact on late-life cognitive disorders","volume":"94","author":"Panza","year":"2023","journal-title":"J Alzheimers Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e75847","DOI":"10.1371\/journal.pone.0075847","article-title":"Patterns of frailty in older adults: comparing results from higher and lower income countries using the Survey of Health, Ageing and Retirement in Europe (SHARE) and the Study on Global AGEing and Adult Health (SAGE)","volume":"8","author":"Harttgen","year":"2013","journal-title":"PLoS ONE."},{"key":"B6","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.archger.2019.02.002","article-title":"Factors associated with the prevalence of sarcopenia and frailty syndrome in elderly university workers","volume":"82","author":"de Amorim","year":"2019","journal-title":"Arch Gerontol Geriatr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1093\/eurpub\/ckaa068","article-title":"The dynamics of frailty and change in socio-economic conditions: evidence for the 65+ in Europe","volume":"30","author":"Sirven","year":"2020","journal-title":"Eur J Public Health."},{"key":"B8","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1093\/ageing\/afaa168","article-title":"Social isolation and loneliness as related to progression and reversion of frailty in the Survey of Health Aging Retirement in Europe (SHARE)","volume":"50","author":"Jarach","year":"2021","journal-title":"Age Ageing."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1016\/S2666-7568(20)30038-6","article-title":"The longitudinal relationship between loneliness, social isolation, and frailty in older adults in England: a prospective analysis","volume":"2","author":"Davies","year":"2021","journal-title":"Lancet Healthy Longev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"811076","DOI":"10.3389\/fnut.2022.811076","article-title":"Dietary customs and social deprivation in an aging population from Southern Italy: a machine learning approach","volume":"9","author":"Tatoli","year":"2022","journal-title":"Front Nutr."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.4081\/jphr.2021.2036","article-title":"Frailty and socioeconomic status: a systematic review","volume":"10","author":"Wang","year":"2021","journal-title":"J Public Health Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1007\/s40200-021-00787-2","article-title":"Prevalence of frailty and associated socio-demographic factors among community-dwelling older people in southwestern Iran: a cross-sectional study","volume":"20","author":"Delbari","year":"2021","journal-title":"J Diabetes Metab Disord."},{"key":"B13","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/agm2.12200","article-title":"The relative impact of socioeconomic position and frailty varies by population setting","volume":"5","author":"Goodyer","year":"2022","journal-title":"Aging Med (Milton)."},{"key":"B14","doi-asserted-by":"publisher","first-page":"a040501","DOI":"10.1101\/cshperspect.a040501","article-title":"Mendelian randomization: concepts and scope","volume":"12","author":"Richmond","year":"2022","journal-title":"Cold Spring Harb Perspect Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e34408","DOI":"10.7554\/eLife.34408.012","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife."},{"key":"B16","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"1000 Genomes Project","year":"2015","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"18262","DOI":"10.1038\/s41598-021-97679-5","article-title":"An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank","volume":"11","author":"Li","year":"2021","journal-title":"Sci Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e13459","DOI":"10.1111\/acel.13459","article-title":"A genome-wide association study of the frailty index highlights brain pathways in ageing","volume":"20","author":"Atkins","year":"2021","journal-title":"Aging Cell."},{"key":"B19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/978-3-030-33330-0_3","article-title":"Epidemiology of frailty in older people","volume":"1216","author":"Rohrmann","year":"2020","journal-title":"Adv Exp Med Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1016\/j.csbj.2022.05.015","article-title":"Statistical methods for Mendelian randomization in genome-wide association studies: a review","volume":"20","author":"Boehm","year":"2022","journal-title":"Comput Struct Biotechnol J."},{"key":"B22","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":"B23","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1001\/jamacardio.2019.4281","article-title":"Heterogeneity between genetic variants as a proxy for pleiotropy in Mendelian randomization","volume":"5","author":"Gill","year":"2020","journal-title":"JAMA Cardiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e1007081","DOI":"10.1371\/journal.pgen.1007081","article-title":"Orienting the causal relationship between imprecisely measured traits using GWAS summary data","volume":"13","author":"Hemani","year":"2017","journal-title":"PLoS Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1590\/1516-3180.2016.0028010616","article-title":"Cardiovascular risk factors associated with frailty syndrome among hospitalized elderly people: a cross-sectional study","volume":"134","author":"Tavares","year":"2016","journal-title":"S\u00e3o Paulo Med J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1111\/ggi.13525","article-title":"Transitional status and modifiable risk of frailty in Japanese older adults: a prospective cohort study","volume":"18","author":"Doi","year":"2018","journal-title":"Geriatr Gerontol Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1136\/jech-2023-220882","article-title":"Associations between modifiable risk factors and frailty: a Mendelian randomisation study","volume":"77","author":"Zhang","year":"2023","journal-title":"J Epidemiol Community Health."},{"key":"B28","doi-asserted-by":"publisher","first-page":"14066","DOI":"10.18632\/aging.205290","article-title":"Obesity, birth weight, and lifestyle factors for frailty: a Mendelian randomization study","volume":"15","author":"Gu","year":"2023","journal-title":"Aging (Albany NY)."},{"key":"B29","doi-asserted-by":"publisher","first-page":"775518","DOI":"10.3389\/fmed.2021.775518","article-title":"Sex-specific association between socioeconomic status, lifestyle, and the risk of frailty among the elderly in China","volume":"8","author":"Wang","year":"2021","journal-title":"Front Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.3390\/healthcare10102079","article-title":"The impact of socioeconomic factors and geriatric syndromes on frailty among elderly people receiving home-based healthcare: a cross-sectional study","volume":"10","author":"Aravantinou-Karlatou","year":"2022","journal-title":"Healthcare."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1093\/gerona\/63.12.1399","article-title":"Life course social and health conditions linked to frailty in Latin American older men and women","volume":"63","author":"Alvarado","year":"2008","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1136\/jech-2015-206406","article-title":"Contribution of health behaviours and clinical factors to socioeconomic differences in frailty among older adults","volume":"70","author":"Soler-Vila","year":"2016","journal-title":"J Epidemiol Community Health."},{"key":"B33","doi-asserted-by":"publisher","first-page":"695","DOI":"10.3233\/WOR-210859","article-title":"Physical demands at work and physical activity are associated with frailty in retirement","volume":"73","author":"van der Valk","year":"2022","journal-title":"Work."},{"key":"B34","doi-asserted-by":"publisher","first-page":"209","DOI":"10.22540\/JFSF-06-209","article-title":"Frailty associations with socioeconomic status, healthcare utilisation and quality of life among older women residing in regional Australia","volume":"6","author":"Yong","year":"2021","journal-title":"J Frailty Sarcopenia Falls."},{"key":"B35","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1177\/1403494813517324","article-title":"Musculoskeletal disorders and occupational exposures: how should we judge the evidence concerning the causal association?","volume":"42","author":"Punnett","year":"2014","journal-title":"Scand J Public Health."},{"key":"B36","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12995-022-00358-y","article-title":"Influence of physically demanding occupations on the development of osteoarthritis of the hip: a systematic review","volume":"17","author":"Unverzagt","year":"2022","journal-title":"J Occup Med Toxicol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2737563","DOI":"10.1155\/2018\/2737563","article-title":"Work intensity, low-grade inflammation, and oxidative status: a comparison between office and slaughterhouse workers","volume":"2018","author":"Zelzer","year":"2018","journal-title":"Oxid Med Cell Longev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"633","DOI":"10.3390\/antiox11040633","article-title":"Occupational health aspects with special focus on physiological differences between office and metalworkers","volume":"11","author":"Tatzber","year":"2022","journal-title":"Antioxidants."},{"key":"B39","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12877-021-02745-2","article-title":"Associations of social isolation, social participation, and loneliness with frailty in older adults in Singapore: a panel data analysis","volume":"22","author":"Ge","year":"2022","journal-title":"BMC Geriatr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1186\/s12877-022-03044-0","article-title":"Associations between loneliness and frailty among older adults: evidence from the China Health and Retirement Longitudinal Study","volume":"22","author":"Sha","year":"2022","journal-title":"BMC Geriatr."},{"key":"B41","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1111\/psyg.12926","article-title":"Relationship between frailty and loneliness among community-dwelling Turkish older people","volume":"23","author":"Altintas","year":"2023","journal-title":"Psychogeriatrics."},{"key":"B42","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1186\/s12888-023-05069-0","article-title":"Associations between constructs related to social relationships and mental health conditions and symptoms: an umbrella review","volume":"23","author":"Pearce","year":"2023","journal-title":"BMC Psychiatry."},{"key":"B43","doi-asserted-by":"publisher","first-page":"353","DOI":"10.19191\/EP20.5-6.S2.137","article-title":"Did social isolation during the SARS-CoV-2 epidemic have an impact on the lifestyles of citizens?","volume":"44","author":"Ferrante","year":"2020","journal-title":"Epidemiol Prev"},{"key":"B44","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1186\/s12889-021-10956-w","article-title":"Social isolation, physical inactivity and inadequate diet among European middle-aged and older adults","volume":"21","author":"Delerue Matos","year":"2021","journal-title":"BMC Public Health."},{"key":"B45","doi-asserted-by":"publisher","first-page":"115266","DOI":"10.1016\/j.psychres.2023.115266","article-title":"Associations of social isolation and loneliness with the onset of insomnia symptoms among middle-aged and older adults in the United States: a population-based cohort study","volume":"325","author":"Qi","year":"2023","journal-title":"Psychiatry Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.jamda.2015.04.008","article-title":"Diabetes and risk of frailty and its potential mechanisms: a prospective cohort study of older adults","volume":"16","author":"Garc\u00eda-Esquinas","year":"2015","journal-title":"J Am Med Dir Assoc."},{"key":"B47","doi-asserted-by":"publisher","first-page":"104207","DOI":"10.1016\/j.archger.2020.104207","article-title":"Association between lifestyle behaviors and frailty in Atlantic Canadian males and females","volume":"91","author":"DeClercq","year":"2020","journal-title":"Arch Gerontol Geriatr."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1344217\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T04:59:40Z","timestamp":1720760380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1344217\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,12]]},"references-count":47,"alternative-id":["10.3389\/fmed.2024.1344217"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2024.1344217","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,12]]},"article-number":"1344217"}}