Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization study
Abstract Background Epidemiological studies have reported an association between amyotrophic lateral sclerosis (ALS) and different autoimmune disorders. This study aims to explore the causal relationship between autoimmune disorders and ALS using Mendelian randomization (MR). Methods To test the gen...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-022-02578-9 |
| _version_ | 1828156134716866560 |
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| author | Paria Alipour Konstantin Senkevich Jay P. Ross Dan Spiegelman Despoina Manousaki Patrick A. Dion Guy A. Rouleau |
| author_facet | Paria Alipour Konstantin Senkevich Jay P. Ross Dan Spiegelman Despoina Manousaki Patrick A. Dion Guy A. Rouleau |
| author_sort | Paria Alipour |
| collection | DOAJ |
| description | Abstract Background Epidemiological studies have reported an association between amyotrophic lateral sclerosis (ALS) and different autoimmune disorders. This study aims to explore the causal relationship between autoimmune disorders and ALS using Mendelian randomization (MR). Methods To test the genetically predicted effects of liability towards immune-related outcomes on ALS risk, we used summary statistics from the largest European genome-wide association studies (GWAS) for these disorders in a two-sample MR setting. To do this, we extracted single nucleotide polymorphisms (SNPs) from the GWAS, which strongly associated with the 12 traits, and queried their effects in a large European ALS GWAS (27,265 cases and 110,881 controls). To avoid bias in our MR instruments related to the complex linkage disequilibrium structure of the human leukocyte antigen (HLA) region, we excluded SNPs within this region from the analyses. We computed inverse-variance weighted (IVW) MR estimates and undertook sensitivity analyses using MR methods robust to horizontal pleiotropy. We also performed a reverse MR analysis testing the causal effects of ALS on the above autoimmune traits. Results After applying Bonferroni correction for multiple testing, our MR analyses showed that the liability to autoimmune disorders does not affect ALS risk. Our reverse MR analysis also did not support the effects of liability to ALS on other autoimmune disorders. The results of the main IVW MR analyses were generally supported by our sensitivity MR analyses. The variance in the exposures explained by the sets of SNPs used as MR instruments ranged from 8.1 × 10−4 to 0.31. Our MR study was well-powered to detect effects as small as an odds ratio (OR) of 1.045 for ALS in the main MR and as small as an OR of 1.32 in the reverse MR. Conclusion Our MR study does not support a relationship between liability to autoimmune disorders and ALS risk in the European population. The associations observed in epidemiological studies could be partly attributed to shared biology or environmental confounders. |
| first_indexed | 2024-04-11T23:05:37Z |
| format | Article |
| id | doaj.art-b1f43af7833e4a98946c077590106e80 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-11T23:05:37Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-b1f43af7833e4a98946c077590106e802022-12-22T03:58:02ZengBMCBMC Medicine1741-70152022-11-012011710.1186/s12916-022-02578-9Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization studyParia Alipour0Konstantin Senkevich1Jay P. Ross2Dan Spiegelman3Despoina Manousaki4Patrick A. Dion5Guy A. Rouleau6Montreal Neurological Institute and Hospital, McGill UniversityMontreal Neurological Institute and Hospital, McGill UniversityMontreal Neurological Institute and Hospital, McGill UniversityMontreal Neurological Institute and Hospital, McGill UniversityDepartment of Biochemistry and Molecular Medicine, University of MontrealMontreal Neurological Institute and Hospital, McGill UniversityMontreal Neurological Institute and Hospital, McGill UniversityAbstract Background Epidemiological studies have reported an association between amyotrophic lateral sclerosis (ALS) and different autoimmune disorders. This study aims to explore the causal relationship between autoimmune disorders and ALS using Mendelian randomization (MR). Methods To test the genetically predicted effects of liability towards immune-related outcomes on ALS risk, we used summary statistics from the largest European genome-wide association studies (GWAS) for these disorders in a two-sample MR setting. To do this, we extracted single nucleotide polymorphisms (SNPs) from the GWAS, which strongly associated with the 12 traits, and queried their effects in a large European ALS GWAS (27,265 cases and 110,881 controls). To avoid bias in our MR instruments related to the complex linkage disequilibrium structure of the human leukocyte antigen (HLA) region, we excluded SNPs within this region from the analyses. We computed inverse-variance weighted (IVW) MR estimates and undertook sensitivity analyses using MR methods robust to horizontal pleiotropy. We also performed a reverse MR analysis testing the causal effects of ALS on the above autoimmune traits. Results After applying Bonferroni correction for multiple testing, our MR analyses showed that the liability to autoimmune disorders does not affect ALS risk. Our reverse MR analysis also did not support the effects of liability to ALS on other autoimmune disorders. The results of the main IVW MR analyses were generally supported by our sensitivity MR analyses. The variance in the exposures explained by the sets of SNPs used as MR instruments ranged from 8.1 × 10−4 to 0.31. Our MR study was well-powered to detect effects as small as an odds ratio (OR) of 1.045 for ALS in the main MR and as small as an OR of 1.32 in the reverse MR. Conclusion Our MR study does not support a relationship between liability to autoimmune disorders and ALS risk in the European population. The associations observed in epidemiological studies could be partly attributed to shared biology or environmental confounders.https://doi.org/10.1186/s12916-022-02578-9Mendelian randomizationAmyotrophic lateral sclerosisAutoimmune disordersCausal relationship |
| spellingShingle | Paria Alipour Konstantin Senkevich Jay P. Ross Dan Spiegelman Despoina Manousaki Patrick A. Dion Guy A. Rouleau Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization study BMC Medicine Mendelian randomization Amyotrophic lateral sclerosis Autoimmune disorders Causal relationship |
| title | Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization study |
| title_full | Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization study |
| title_fullStr | Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization study |
| title_full_unstemmed | Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization study |
| title_short | Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization study |
| title_sort | investigation of the causal relationship between als and autoimmune disorders a mendelian randomization study |
| topic | Mendelian randomization Amyotrophic lateral sclerosis Autoimmune disorders Causal relationship |
| url | https://doi.org/10.1186/s12916-022-02578-9 |
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