Thyroiditis and human blood metabolites: A mendelian randomization study
Background: The risk factors for thyroiditis, an inflammatory disease with a complex etiology, remain poorly understood. Blood metabolites are known to change during thyroiditis development, suggesting a close relationship between blood metabolites and thyroiditis progression. However, evidence for...
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Society of Medical Biochemists of Serbia, Belgrade
2025-01-01
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| Series: | Journal of Medical Biochemistry |
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| Online Access: | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2025/1452-82582504872S.pdf |
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| author | Shao Lijie Liu Siqi Song Yongfu Han Shaoyu Ma Yue Kunpeng Yang Zhang Jingbin Qi Bingxue Guo Yan Lu Xiaodan |
| author_facet | Shao Lijie Liu Siqi Song Yongfu Han Shaoyu Ma Yue Kunpeng Yang Zhang Jingbin Qi Bingxue Guo Yan Lu Xiaodan |
| author_sort | Shao Lijie |
| collection | DOAJ |
| description | Background: The risk factors for thyroiditis, an inflammatory disease with a complex etiology, remain poorly understood. Blood metabolites are known to change during thyroiditis development, suggesting a close relationship between blood metabolites and thyroiditis progression. However, evidence for a causal link is lacking. We employed Mendelian randomization (MR) methodology to systematically investigate the putative causal relationships between blood metabolite profiles and two clinically distinct thyroiditis phenotypes-subacute and autoimmune thyroiditis-providing insights into their metabolic underpinnings. Methods: We analyzed genomic and health data from 88 million Finnish Biobank participants in the Genome-Wide Association Study (GWAS). The primary analytical method was random-effects inverse variance weighting (IVW), supplemented by the weighted median method (WME) and Mr-Egger. We implemented comprehensive sensitivity analyses encompassing Cochran's Q test, Mr-Egger intercept, leave-one-out analysis (LOO), and Mr-PRESSO to assess heterogeneity, pleiotropy, and outliers. Extended genetic investigations incorporated the linkage disequilibrium score regression (LDSC) method, multivariable Mr (MVMR), and metabolic pathway analyses to provide deeper mechanistic insights. Results: Ten metabolites were significantly associated with autoimmune thyroiditis, and fifteen with subacute thyroiditis. Nonadecanoate (19:0) and 1-palmitoylglycerophosphoinositol* were found to directly affect subacute thyroiditis. MVMR analyses identified pelargonate (9:0), carnitine, and ADpSGEGDFXAEGGGVR* as having an independent and direct effect on autoimmune thyroiditis. Additionally, metabolic pathways such as neomycin, kanamycin, and gentamicin biosynthesis, histidine metabolism, and starch and sucrose metabolism were linked to autoimmune thyroiditis, while phenylalanine, tyrosine, tryptophan biosynthesis, phenylalanine metabolism, and arginine biosynthesis were associated with subacute thyroiditis. Conclusions: Our findings establish causal relationships between circulating metabolites and thyroiditis, revealing novel mechanistic insights through integrated genomic and metabolomic analyses. These results not only advance our understanding of thyroiditis pathogenesis but also suggest potential biomarkers for disease screening and therapeutic targets for intervention. |
| format | Article |
| id | doaj-art-ff7b1440ee464a1a9f420e6c6d621745 |
| institution | Kabale University |
| issn | 1452-8258 1452-8266 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Society of Medical Biochemists of Serbia, Belgrade |
| record_format | Article |
| series | Journal of Medical Biochemistry |
| spelling | doaj-art-ff7b1440ee464a1a9f420e6c6d6217452025-08-20T03:28:51ZengSociety of Medical Biochemists of Serbia, BelgradeJournal of Medical Biochemistry1452-82581452-82662025-01-0144487288510.5937/jomb0-562171452-82582504872SThyroiditis and human blood metabolites: A mendelian randomization studyShao Lijie0Liu Siqi1Song Yongfu2Han Shaoyu3Ma Yue4Kunpeng Yang5Zhang Jingbin6Qi Bingxue7Guo Yan8Lu Xiaodan9Changchun University of Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Changchun, ChinaPrecision Medicine Center, Jilin Province People's Hospital, Changchun, ChinaChangchun University of Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Changchun, ChinaShanghai Lixin University of Accounting and Finance, Shanghai, ChinaChangchun University of Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Changchun, ChinaChangchun University of Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Changchun, ChinaPrecision Medicine Center, Jilin Province People's Hospital, Changchun, ChinaPrecision Medicine Center, Jilin Province People's Hospital, Changchun, ChinaChangchun University of Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Changchun, ChinaChangchun University of Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Changchun, ChinaBackground: The risk factors for thyroiditis, an inflammatory disease with a complex etiology, remain poorly understood. Blood metabolites are known to change during thyroiditis development, suggesting a close relationship between blood metabolites and thyroiditis progression. However, evidence for a causal link is lacking. We employed Mendelian randomization (MR) methodology to systematically investigate the putative causal relationships between blood metabolite profiles and two clinically distinct thyroiditis phenotypes-subacute and autoimmune thyroiditis-providing insights into their metabolic underpinnings. Methods: We analyzed genomic and health data from 88 million Finnish Biobank participants in the Genome-Wide Association Study (GWAS). The primary analytical method was random-effects inverse variance weighting (IVW), supplemented by the weighted median method (WME) and Mr-Egger. We implemented comprehensive sensitivity analyses encompassing Cochran's Q test, Mr-Egger intercept, leave-one-out analysis (LOO), and Mr-PRESSO to assess heterogeneity, pleiotropy, and outliers. Extended genetic investigations incorporated the linkage disequilibrium score regression (LDSC) method, multivariable Mr (MVMR), and metabolic pathway analyses to provide deeper mechanistic insights. Results: Ten metabolites were significantly associated with autoimmune thyroiditis, and fifteen with subacute thyroiditis. Nonadecanoate (19:0) and 1-palmitoylglycerophosphoinositol* were found to directly affect subacute thyroiditis. MVMR analyses identified pelargonate (9:0), carnitine, and ADpSGEGDFXAEGGGVR* as having an independent and direct effect on autoimmune thyroiditis. Additionally, metabolic pathways such as neomycin, kanamycin, and gentamicin biosynthesis, histidine metabolism, and starch and sucrose metabolism were linked to autoimmune thyroiditis, while phenylalanine, tyrosine, tryptophan biosynthesis, phenylalanine metabolism, and arginine biosynthesis were associated with subacute thyroiditis. Conclusions: Our findings establish causal relationships between circulating metabolites and thyroiditis, revealing novel mechanistic insights through integrated genomic and metabolomic analyses. These results not only advance our understanding of thyroiditis pathogenesis but also suggest potential biomarkers for disease screening and therapeutic targets for intervention.https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2025/1452-82582504872S.pdfautoimmune thyroiditissubacute thyroiditismendelian randomization analysismetabolites |
| spellingShingle | Shao Lijie Liu Siqi Song Yongfu Han Shaoyu Ma Yue Kunpeng Yang Zhang Jingbin Qi Bingxue Guo Yan Lu Xiaodan Thyroiditis and human blood metabolites: A mendelian randomization study Journal of Medical Biochemistry autoimmune thyroiditis subacute thyroiditis mendelian randomization analysis metabolites |
| title | Thyroiditis and human blood metabolites: A mendelian randomization study |
| title_full | Thyroiditis and human blood metabolites: A mendelian randomization study |
| title_fullStr | Thyroiditis and human blood metabolites: A mendelian randomization study |
| title_full_unstemmed | Thyroiditis and human blood metabolites: A mendelian randomization study |
| title_short | Thyroiditis and human blood metabolites: A mendelian randomization study |
| title_sort | thyroiditis and human blood metabolites a mendelian randomization study |
| topic | autoimmune thyroiditis subacute thyroiditis mendelian randomization analysis metabolites |
| url | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2025/1452-82582504872S.pdf |
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