Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis
Background Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia‐related traits using genetic data. M...
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| creator | Di, Wang Luyao, Yang Chengwei, Yang Valtonen, Anu M. Juha‐Pekka, Kulmala Ying, Gao |
| description | Background
Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia‐related traits using genetic data.
Methods
A two‐sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome‐wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR‐Egger, Weighted Mode, Simple Mode, and MR‐PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR‐Egger regression, and “leave‐one‐out” sensitivity analyses.
Results
The IVM‐MR analysis showed a casual association between genetically predicted circulating levels of interleukin‐16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980–1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948–0.995, p = .020). Additionally, interferon‐gamma‐induced protein 10 (IP‐10), interleukin‐1‐beta (IL‐1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin‐12 (IL‐12), and interleukin‐5 (IL‐5) with grip strength. Comparable results were confirmed via the MR‐Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates.
Conclusion
The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context. |
| doi_str_mv | 10.1002/tox.24206 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3153567863</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3054810495</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3866-6f682d9d42c42529ab0c9d93decf310248fba568c3638b592e86827652147323</originalsourceid><addsrcrecordid>eNqF0TtPHDEUBWArAoVHUuQPIEs0oRjwe2w6hMhDAtFskW7k8dwhBq-92DOCza-PYQlFJETlW3znSNZB6Aslx5QQdjKlx2MmGFEf0C6VjDUta_XW800aQTTdQXul3BJCjJLqI9rhWkhitNxF9xePq5Cyjzd4-g3Y2bnYgIOPd7iH6QEgYuezm4OdnoxbT-nORyjYxgEXm11aQfQWT9n6qZziM3wFcYDgbcS5mrT0f2o0xRqwYV18-YS2RxsKfH5599Hi28Xi_Edzef395_nZZeO4VqpRo9JsMINgTjDJjO2JM4PhA7iRU8KEHnsrlXZccd1Lw0DXQKsko6LljO-jr5vaVU73M5SpW_riIAQbIc2l41RyqVqt-LuUGcGoVi0xlR7-R2_TnOvPaiGRQlMijKzqaKNcTqVkGLtV9kub1x0l3dNiXV2se16s2oOXxrlfwvAq_01UwckGPPgA67ebusX1r03lX_T2n5s</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3054810495</pqid></control><display><type>article</type><title>Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Di, Wang ; Luyao, Yang ; Chengwei, Yang ; Valtonen, Anu M. ; Juha‐Pekka, Kulmala ; Ying, Gao</creator><creatorcontrib>Di, Wang ; Luyao, Yang ; Chengwei, Yang ; Valtonen, Anu M. ; Juha‐Pekka, Kulmala ; Ying, Gao</creatorcontrib><description>Background
Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia‐related traits using genetic data.
Methods
A two‐sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome‐wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR‐Egger, Weighted Mode, Simple Mode, and MR‐PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR‐Egger regression, and “leave‐one‐out” sensitivity analyses.
Results
The IVM‐MR analysis showed a casual association between genetically predicted circulating levels of interleukin‐16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980–1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948–0.995, p = .020). Additionally, interferon‐gamma‐induced protein 10 (IP‐10), interleukin‐1‐beta (IL‐1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin‐12 (IL‐12), and interleukin‐5 (IL‐5) with grip strength. Comparable results were confirmed via the MR‐Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates.
Conclusion
The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.24206</identifier><identifier>PMID: 38450985</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>ancestry ; appendicular lean mass ; circulating cytokines ; Circulation ; Cytokines ; ecotoxicology ; Ethnic factors ; Genomes ; Grip strength ; Growth factors ; Hepatocyte growth factor ; Hepatocytes ; Heterogeneity ; Inflammation ; inflammatory cytokines ; interleukin-12 ; interleukin-5 ; Interleukins ; Median (statistics) ; Mendelian randomization ; Minority & ethnic groups ; muscle strength ; Nucleotides ; Observational studies ; Pleiotropy ; Randomization ; Sarcopenia ; Sensitivity analysis ; Single-nucleotide polymorphism ; Statistical analysis ; Therapeutic targets ; therapeutics ; variance ; Vascular endothelial growth factor ; vascular endothelial growth factors</subject><ispartof>Environmental toxicology, 2024-06, Vol.39 (6), p.3434-3447</ispartof><rights>2024 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3866-6f682d9d42c42529ab0c9d93decf310248fba568c3638b592e86827652147323</citedby><cites>FETCH-LOGICAL-c3866-6f682d9d42c42529ab0c9d93decf310248fba568c3638b592e86827652147323</cites><orcidid>0000-0003-1881-4689 ; 0000-0002-6214-2085 ; 0009-0008-5538-9099 ; 0000-0003-1440-0681</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Ftox.24206$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.24206$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38450985$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di, Wang</creatorcontrib><creatorcontrib>Luyao, Yang</creatorcontrib><creatorcontrib>Chengwei, Yang</creatorcontrib><creatorcontrib>Valtonen, Anu M.</creatorcontrib><creatorcontrib>Juha‐Pekka, Kulmala</creatorcontrib><creatorcontrib>Ying, Gao</creatorcontrib><title>Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>Background
Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia‐related traits using genetic data.
Methods
A two‐sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome‐wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR‐Egger, Weighted Mode, Simple Mode, and MR‐PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR‐Egger regression, and “leave‐one‐out” sensitivity analyses.
Results
The IVM‐MR analysis showed a casual association between genetically predicted circulating levels of interleukin‐16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980–1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948–0.995, p = .020). Additionally, interferon‐gamma‐induced protein 10 (IP‐10), interleukin‐1‐beta (IL‐1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin‐12 (IL‐12), and interleukin‐5 (IL‐5) with grip strength. Comparable results were confirmed via the MR‐Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates.
Conclusion
The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context.</description><subject>ancestry</subject><subject>appendicular lean mass</subject><subject>circulating cytokines</subject><subject>Circulation</subject><subject>Cytokines</subject><subject>ecotoxicology</subject><subject>Ethnic factors</subject><subject>Genomes</subject><subject>Grip strength</subject><subject>Growth factors</subject><subject>Hepatocyte growth factor</subject><subject>Hepatocytes</subject><subject>Heterogeneity</subject><subject>Inflammation</subject><subject>inflammatory cytokines</subject><subject>interleukin-12</subject><subject>interleukin-5</subject><subject>Interleukins</subject><subject>Median (statistics)</subject><subject>Mendelian randomization</subject><subject>Minority & ethnic groups</subject><subject>muscle strength</subject><subject>Nucleotides</subject><subject>Observational studies</subject><subject>Pleiotropy</subject><subject>Randomization</subject><subject>Sarcopenia</subject><subject>Sensitivity analysis</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><subject>Therapeutic targets</subject><subject>therapeutics</subject><subject>variance</subject><subject>Vascular endothelial growth factor</subject><subject>vascular endothelial growth factors</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqF0TtPHDEUBWArAoVHUuQPIEs0oRjwe2w6hMhDAtFskW7k8dwhBq-92DOCza-PYQlFJETlW3znSNZB6Aslx5QQdjKlx2MmGFEf0C6VjDUta_XW800aQTTdQXul3BJCjJLqI9rhWkhitNxF9xePq5Cyjzd4-g3Y2bnYgIOPd7iH6QEgYuezm4OdnoxbT-nORyjYxgEXm11aQfQWT9n6qZziM3wFcYDgbcS5mrT0f2o0xRqwYV18-YS2RxsKfH5599Hi28Xi_Edzef395_nZZeO4VqpRo9JsMINgTjDJjO2JM4PhA7iRU8KEHnsrlXZccd1Lw0DXQKsko6LljO-jr5vaVU73M5SpW_riIAQbIc2l41RyqVqt-LuUGcGoVi0xlR7-R2_TnOvPaiGRQlMijKzqaKNcTqVkGLtV9kub1x0l3dNiXV2se16s2oOXxrlfwvAq_01UwckGPPgA67ebusX1r03lX_T2n5s</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Di, Wang</creator><creator>Luyao, Yang</creator><creator>Chengwei, Yang</creator><creator>Valtonen, Anu M.</creator><creator>Juha‐Pekka, Kulmala</creator><creator>Ying, Gao</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QH</scope><scope>7ST</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M7N</scope><scope>SOI</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0003-1881-4689</orcidid><orcidid>https://orcid.org/0000-0002-6214-2085</orcidid><orcidid>https://orcid.org/0009-0008-5538-9099</orcidid><orcidid>https://orcid.org/0000-0003-1440-0681</orcidid></search><sort><creationdate>202406</creationdate><title>Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis</title><author>Di, Wang ; Luyao, Yang ; Chengwei, Yang ; Valtonen, Anu M. ; Juha‐Pekka, Kulmala ; Ying, Gao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3866-6f682d9d42c42529ab0c9d93decf310248fba568c3638b592e86827652147323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>ancestry</topic><topic>appendicular lean mass</topic><topic>circulating cytokines</topic><topic>Circulation</topic><topic>Cytokines</topic><topic>ecotoxicology</topic><topic>Ethnic factors</topic><topic>Genomes</topic><topic>Grip strength</topic><topic>Growth factors</topic><topic>Hepatocyte growth factor</topic><topic>Hepatocytes</topic><topic>Heterogeneity</topic><topic>Inflammation</topic><topic>inflammatory cytokines</topic><topic>interleukin-12</topic><topic>interleukin-5</topic><topic>Interleukins</topic><topic>Median (statistics)</topic><topic>Mendelian randomization</topic><topic>Minority & ethnic groups</topic><topic>muscle strength</topic><topic>Nucleotides</topic><topic>Observational studies</topic><topic>Pleiotropy</topic><topic>Randomization</topic><topic>Sarcopenia</topic><topic>Sensitivity analysis</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><topic>Therapeutic targets</topic><topic>therapeutics</topic><topic>variance</topic><topic>Vascular endothelial growth factor</topic><topic>vascular endothelial growth factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di, Wang</creatorcontrib><creatorcontrib>Luyao, Yang</creatorcontrib><creatorcontrib>Chengwei, Yang</creatorcontrib><creatorcontrib>Valtonen, Anu M.</creatorcontrib><creatorcontrib>Juha‐Pekka, Kulmala</creatorcontrib><creatorcontrib>Ying, Gao</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di, Wang</au><au>Luyao, Yang</au><au>Chengwei, Yang</au><au>Valtonen, Anu M.</au><au>Juha‐Pekka, Kulmala</au><au>Ying, Gao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ Toxicol</addtitle><date>2024-06</date><risdate>2024</risdate><volume>39</volume><issue>6</issue><spage>3434</spage><epage>3447</epage><pages>3434-3447</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><abstract>Background
Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia‐related traits using genetic data.
Methods
A two‐sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome‐wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR‐Egger, Weighted Mode, Simple Mode, and MR‐PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR‐Egger regression, and “leave‐one‐out” sensitivity analyses.
Results
The IVM‐MR analysis showed a casual association between genetically predicted circulating levels of interleukin‐16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980–1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948–0.995, p = .020). Additionally, interferon‐gamma‐induced protein 10 (IP‐10), interleukin‐1‐beta (IL‐1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin‐12 (IL‐12), and interleukin‐5 (IL‐5) with grip strength. Comparable results were confirmed via the MR‐Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates.
Conclusion
The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>38450985</pmid><doi>10.1002/tox.24206</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-1881-4689</orcidid><orcidid>https://orcid.org/0000-0002-6214-2085</orcidid><orcidid>https://orcid.org/0009-0008-5538-9099</orcidid><orcidid>https://orcid.org/0000-0003-1440-0681</orcidid></addata></record> |
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| subjects | ancestry appendicular lean mass circulating cytokines Circulation Cytokines ecotoxicology Ethnic factors Genomes Grip strength Growth factors Hepatocyte growth factor Hepatocytes Heterogeneity Inflammation inflammatory cytokines interleukin-12 interleukin-5 Interleukins Median (statistics) Mendelian randomization Minority & ethnic groups muscle strength Nucleotides Observational studies Pleiotropy Randomization Sarcopenia Sensitivity analysis Single-nucleotide polymorphism Statistical analysis Therapeutic targets therapeutics variance Vascular endothelial growth factor vascular endothelial growth factors |
| title | Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis |
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