{"doi":"10.1101/2020.07.20.211276","title":"Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types","abstract":"ABSTRACT Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely neuron projection morphogenesis, membrane trafficking , and signal transduction mediated by ribonucleotides . We also found that genomic risk in ALS maps consistently to GABAergic cortical interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated five differentially expressed genes ( ATG16L2, ACSL5, MAP1LC3A, PLXNB2 , and SCFD1 ) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120721,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9338,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230757,"name":"Sara Bandrés‐Ciga","orcid":"0000-0003-0056-1361","position":1,"is_corresponding":false},{"id":512135,"name":"Rebekah G. Langston","orcid":"0000-0003-0123-7934","position":2,"is_corresponding":false},{"id":280326,"name":"Jonggeol J. Kim","orcid":null,"position":3,"is_corresponding":false},{"id":315173,"name":"Shing Wan Choi","orcid":"0000-0003-2215-3238","position":4,"is_corresponding":false},{"id":45804,"name":"Regina Hertfelder Reynolds","orcid":"0000-0001-6470-7919","position":5,"is_corresponding":false},{"id":243601,"name":"Yevgeniya Abramzon","orcid":null,"position":6,"is_corresponding":false},{"id":296792,"name":"Ramita Dewan","orcid":null,"position":7,"is_corresponding":false},{"id":295303,"name":"Sarah Ahmed","orcid":"0000-0003-0247-2557","position":8,"is_corresponding":false},{"id":291677,"name":"John E. Landers","orcid":"0000-0001-8084-5043","position":9,"is_corresponding":false},{"id":240476,"name":"Ruth Chia","orcid":"0000-0002-4709-7423","position":10,"is_corresponding":false},{"id":45812,"name":"Mina Ryten","orcid":"0000-0001-9520-6957","position":11,"is_corresponding":false},{"id":238914,"name":"Mark Cookson","orcid":null,"position":12,"is_corresponding":false},{"id":21711,"name":"Michael A. Nalls","orcid":null,"position":13,"is_corresponding":false},{"id":347586,"name":"Adriano Chiò","orcid":"0000-0001-9579-5341","position":14,"is_corresponding":false},{"id":240475,"name":"Bryan J. Traynor","orcid":"0000-0003-0527-2446","position":15,"is_corresponding":false},{"id":236478,"name":"Sara Sáez-Atiénzar","orcid":"0000-0002-1524-9584","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:14:38.147936Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}