Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study
Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study.Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We a...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1129247/full |
| _version_ | 1827965814404284416 |
|---|---|
| author | Meiling Liu Ping Luo Lihua Liu Xianping Wei Xue Bai Jicui Li Linlin Wu Manyu Luo |
| author_facet | Meiling Liu Ping Luo Lihua Liu Xianping Wei Xue Bai Jicui Li Linlin Wu Manyu Luo |
| author_sort | Meiling Liu |
| collection | DOAJ |
| description | Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study.Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran’s Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction.Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66–0.89, and p = 3.66 × 10−4), SS (OR: 0.75, CI: 0.58–0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68–0.88, and p = 9.85 × 10−5), hypothyroidism (OR: 0.84, 95% CI: 0.78–0.91, and p = 7,08 × 10−6), hyperthyroidism (OR: 0.60, 95% CI: 0.44–0.83, and p = 1.90 × 10−3), sarcoidosis (OR: 0.67, 95% CI: 0.54–0.83, and p = 2.60 × 10−4), and IPF (OR: 0.41, 95% CI: 0.29–0.58, and p = 4.11 × 10−7) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18–1.94, and p = 9.66 × 10−4). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62–1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37–2.54, and p = 8.01 × 10−5).Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs. |
| first_indexed | 2024-04-09T17:39:18Z |
| format | Article |
| id | doaj.art-24301392e120421198e9a99642c60d08 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-09T17:39:18Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-24301392e120421198e9a99642c60d082023-04-17T06:00:39ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-04-011410.3389/fgene.2023.11292471129247Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization studyMeiling LiuPing LuoLihua LiuXianping WeiXue BaiJicui LiLinlin WuManyu LuoObjective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study.Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran’s Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction.Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66–0.89, and p = 3.66 × 10−4), SS (OR: 0.75, CI: 0.58–0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68–0.88, and p = 9.85 × 10−5), hypothyroidism (OR: 0.84, 95% CI: 0.78–0.91, and p = 7,08 × 10−6), hyperthyroidism (OR: 0.60, 95% CI: 0.44–0.83, and p = 1.90 × 10−3), sarcoidosis (OR: 0.67, 95% CI: 0.54–0.83, and p = 2.60 × 10−4), and IPF (OR: 0.41, 95% CI: 0.29–0.58, and p = 4.11 × 10−7) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18–1.94, and p = 9.66 × 10−4). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62–1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37–2.54, and p = 8.01 × 10−5).Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.https://www.frontiersin.org/articles/10.3389/fgene.2023.1129247/fullMendelian randomizationtelomere lengthimmune-mediated inflammatory diseasesgenetic variantscausal effect |
| spellingShingle | Meiling Liu Ping Luo Lihua Liu Xianping Wei Xue Bai Jicui Li Linlin Wu Manyu Luo Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study Frontiers in Genetics Mendelian randomization telomere length immune-mediated inflammatory diseases genetic variants causal effect |
| title | Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study |
| title_full | Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study |
| title_fullStr | Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study |
| title_full_unstemmed | Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study |
| title_short | Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study |
| title_sort | immune mediated inflammatory diseases and leukocyte telomere length a mendelian randomization study |
| topic | Mendelian randomization telomere length immune-mediated inflammatory diseases genetic variants causal effect |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1129247/full |
| work_keys_str_mv | AT meilingliu immunemediatedinflammatorydiseasesandleukocytetelomerelengthamendelianrandomizationstudy AT pingluo immunemediatedinflammatorydiseasesandleukocytetelomerelengthamendelianrandomizationstudy AT lihualiu immunemediatedinflammatorydiseasesandleukocytetelomerelengthamendelianrandomizationstudy AT xianpingwei immunemediatedinflammatorydiseasesandleukocytetelomerelengthamendelianrandomizationstudy AT xuebai immunemediatedinflammatorydiseasesandleukocytetelomerelengthamendelianrandomizationstudy AT jicuili immunemediatedinflammatorydiseasesandleukocytetelomerelengthamendelianrandomizationstudy AT linlinwu immunemediatedinflammatorydiseasesandleukocytetelomerelengthamendelianrandomizationstudy AT manyuluo immunemediatedinflammatorydiseasesandleukocytetelomerelengthamendelianrandomizationstudy |