Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study
BackgroundHypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between thyroid function and RA, we conducted a two-Sample bidirectional Mendelian Randomization (MR) study.MethodsSingle nucleoti...
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238757/full |
| _version_ | 1797449572568530944 |
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| author | Peng Gu Peng Gu Bin Pu Bin Pu YangCheng Ma Dan Yue Qiao Xin HaiShan Li Teng Liu XiaoHui Zheng ChongZhi Ouyang |
| author_facet | Peng Gu Peng Gu Bin Pu Bin Pu YangCheng Ma Dan Yue Qiao Xin HaiShan Li Teng Liu XiaoHui Zheng ChongZhi Ouyang |
| author_sort | Peng Gu |
| collection | DOAJ |
| description | BackgroundHypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between thyroid function and RA, we conducted a two-Sample bidirectional Mendelian Randomization (MR) study.MethodsSingle nucleotide polymorphisms associated with six phenotypes were selected from the FinnGen biobank database, The ThyroidOmics Consortium database, and the IEU Open GWAS database. For the forward MR analysis, we selected hypothyroidism (N=213,390), Graves’ disease (GD) (N=199,034), other types of hyperthyroidism (N=190,799), free thyroxine (FT4, N=49,269), and thyroid-stimulating hormone (TSH, N=54,288) as the five related thyroid function phenotypes for exposure, with RA (N=58,284) as the outcome. Reverse MR analysis selected RA as the exposure and five phenotypes of thyroid function as the outcome. The Inverse variance weighting (IVW) method was used as the primary analysis method, supplemented by weighted median (WM) and MR-Egger methods. Cochran’s Q test, MR-PRESSO, MR-Egger regression methods, and leave-one-out analysis were employed to assess sensitivity and pleiotropy.ResultsForward MR evidence indicates that genetic susceptibility to hypothyroidism is associated with an increased risk of RA (ORIvw=1.758, P=7.61×10-5). Reverse MR evidence suggests that genetic susceptibility to RA is associated with an increased risk of hypothyroidism (ORIvw=1.274, P=3.88×10-20), GD (ORIvw=1.269, P=8.15×10-05), and other types of hyperthyroidism (ORIvw=1.141, P=1.80×10-03). There is no evidence to support a forward or reverse causal relationship between genetic susceptibility to RA and FT4, TSH.ConclusionOur results provide genetic evidence supporting bidirectional causal relationships between thyroid function and RA. These findings inform preventive strategies and interventions targeting RA and thyroid dysfunction. |
| first_indexed | 2024-03-09T14:27:55Z |
| format | Article |
| id | doaj.art-8b6fc75839e44ffe9eef9acb7bcd4a0e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T14:27:55Z |
| publishDate | 2023-11-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-8b6fc75839e44ffe9eef9acb7bcd4a0e2023-11-28T05:28:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12387571238757Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization studyPeng Gu0Peng Gu1Bin Pu2Bin Pu3YangCheng Ma4Dan Yue5Qiao Xin6HaiShan Li7Teng Liu8XiaoHui Zheng9ChongZhi Ouyang10The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaFirst School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaCollege of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaGraduated School, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, ChinaFirst School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaFirst School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, ChinaBackgroundHypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between thyroid function and RA, we conducted a two-Sample bidirectional Mendelian Randomization (MR) study.MethodsSingle nucleotide polymorphisms associated with six phenotypes were selected from the FinnGen biobank database, The ThyroidOmics Consortium database, and the IEU Open GWAS database. For the forward MR analysis, we selected hypothyroidism (N=213,390), Graves’ disease (GD) (N=199,034), other types of hyperthyroidism (N=190,799), free thyroxine (FT4, N=49,269), and thyroid-stimulating hormone (TSH, N=54,288) as the five related thyroid function phenotypes for exposure, with RA (N=58,284) as the outcome. Reverse MR analysis selected RA as the exposure and five phenotypes of thyroid function as the outcome. The Inverse variance weighting (IVW) method was used as the primary analysis method, supplemented by weighted median (WM) and MR-Egger methods. Cochran’s Q test, MR-PRESSO, MR-Egger regression methods, and leave-one-out analysis were employed to assess sensitivity and pleiotropy.ResultsForward MR evidence indicates that genetic susceptibility to hypothyroidism is associated with an increased risk of RA (ORIvw=1.758, P=7.61×10-5). Reverse MR evidence suggests that genetic susceptibility to RA is associated with an increased risk of hypothyroidism (ORIvw=1.274, P=3.88×10-20), GD (ORIvw=1.269, P=8.15×10-05), and other types of hyperthyroidism (ORIvw=1.141, P=1.80×10-03). There is no evidence to support a forward or reverse causal relationship between genetic susceptibility to RA and FT4, TSH.ConclusionOur results provide genetic evidence supporting bidirectional causal relationships between thyroid function and RA. These findings inform preventive strategies and interventions targeting RA and thyroid dysfunction.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238757/fullMendelian randomizationrheumatoid arthritishyperthyroidismhypothyroidismfree thyroxinethyroid-stimulating hormone |
| spellingShingle | Peng Gu Peng Gu Bin Pu Bin Pu YangCheng Ma Dan Yue Qiao Xin HaiShan Li Teng Liu XiaoHui Zheng ChongZhi Ouyang Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study Frontiers in Immunology Mendelian randomization rheumatoid arthritis hyperthyroidism hypothyroidism free thyroxine thyroid-stimulating hormone |
| title | Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study |
| title_full | Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study |
| title_fullStr | Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study |
| title_full_unstemmed | Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study |
| title_short | Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study |
| title_sort | appraising the causal relationship between thyroid function and rheumatoid arthritis a two sample bidirectional mendelian randomization study |
| topic | Mendelian randomization rheumatoid arthritis hyperthyroidism hypothyroidism free thyroxine thyroid-stimulating hormone |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238757/full |
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