دورية أكاديمية
Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases
| العنوان: | Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases |
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| المؤلفون: | Chun Yu Li, Tian Mi Yang, Ru Wei Ou, Qian Qian Wei, Hui Fang Shang |
| المصدر: | BMC Medicine, Vol 19, Iss 1, Pp 1-11 (2021) |
| بيانات النشر: | BMC |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Amyotrophic lateral sclerosis, Autoimmunity, Pleiotropy, Conditional false discovery rate, Genome-wide association study, Medicine |
| الوصف: | Background Epidemiological and clinical studies have suggested comorbidity between amyotrophic lateral sclerosis (ALS) and autoimmune disorders. However, little is known about their shared genetic architecture. Methods To examine the relation between ALS and 10 autoimmune diseases, including asthma, celiac disease (CeD), Crohn’s disease (CD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and ulcerative colitis (UC), and identify shared risk loci, we first estimated the genetic correlation using summary statistics from genome-wide association studies, and then analyzed the genetic enrichment leveraging the conditional false discovery rate statistical method. Results We identified a significant positive genetic correlation between ALS and CeD, MS, RA, and SLE, as well as a significant negative genetic correlation between ALS and IBD, UC, and CD. Robust genetic enrichment was observed between ALS and CeD and MS, and moderate enrichment was found between ALS and UC and T1D. Thirteen shared genetic loci were identified, among which five were suggestively significant in another ALS GWAS, namely rs3828599 (GPX3), rs3849943 (C9orf72), rs7154847 (G2E3), rs6571361 (SCFD1), and rs9903355 (GGNBP2). By integrating cis-expression quantitative trait loci analyses in Braineac and GTEx, we further identified GGNBP2, ATXN3, and SLC9A8 as novel ALS risk genes. Functional enrichment analysis indicated that the shared risk genes were involved in four pathways including membrane trafficking, vesicle-mediated transport, ER to Golgi anterograde transport, and transport to the Golgi and subsequent modification. Conclusions Our findings demonstrate a specific genetic correlation between ALS and autoimmune diseases and identify shared risk loci, including three novel ALS risk genes. These results provide a better understanding for the pleiotropy of ALS and have implications for future therapeutic trials. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1741-7015 |
| العلاقة: | https://doi.org/10.1186/s12916-021-01903-yTest; https://doaj.org/toc/1741-7015Test; https://doaj.org/article/63c80494230e442e923e9840a19f08e4Test |
| DOI: | 10.1186/s12916-021-01903-y |
| الإتاحة: | https://doi.org/10.1186/s12916-021-01903-yTest https://doaj.org/article/63c80494230e442e923e9840a19f08e4Test |
| رقم الانضمام: | edsbas.57366C6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17417015 |
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| DOI: | 10.1186/s12916-021-01903-y |