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However, little is known about their shared genetic architecture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To examine the relation between ALS and 10 autoimmune diseases, including asthma, celiac disease (CeD), Crohn\u2019s disease (CD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and\u00a0ulcerative 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (<jats:italic>GPX3<\/jats:italic>), rs3849943 (<jats:italic>C9orf72<\/jats:italic>), rs7154847 (<jats:italic>G2E3<\/jats:italic>), rs6571361 (<jats:italic>SCFD1<\/jats:italic>), and rs9903355 (<jats:italic>GGNBP2<\/jats:italic>). By integrating<jats:italic>cis<\/jats:italic>-expression quantitative trait loci analyses in Braineac and GTEx, we further identified<jats:italic>GGNBP2<\/jats:italic>,<jats:italic>ATXN3<\/jats:italic>, and<jats:italic>SLC9A8<\/jats:italic>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\u00a0transport to the Golgi and subsequent modification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12916-021-01903-y","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T02:03:40Z","timestamp":1612490620000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases"],"prefix":"10.1186","volume":"19","author":[{"given":"Chun Yu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian Mi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru Wei","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian Qian","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0947-1151","authenticated-orcid":false,"given":"Hui Fang","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"issue":"2","key":"1903_CR1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1056\/NEJMra1603471","volume":"377","author":"RH Brown","year":"2017","unstructured":"Brown RH, Al-Chalabi A. 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