{"id":"https://openalex.org/W7225789264","doi":"https://doi.org/10.64898/2026.11.10.764216","title":"Investigating the causal and consequential role of the nuclear encoded mitochondrial genome in Amyotrophic Lateral Sclerosis","display_name":"Investigating the causal and consequential role of the nuclear encoded mitochondrial genome in Amyotrophic Lateral Sclerosis","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225789264","doi":"https://doi.org/10.64898/2026.11.10.764216"},"language":"en","primary_location":{"id":"doi:10.64898/2026.11.10.764216","doi":"https://doi.org/10.64898/2026.11.10.764216","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.10.764216","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.64898/2026.11.10.764216","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5061885486","display_name":"Aminah Tasnim Ali","orcid":"https://orcid.org/0000-0003-1089-9278","observed_orcids":["https://orcid.org/0000-0003-1089-9278"]},"institutions":[{"id":"https://openalex.org/I183935753","display_name":"King's College London","ror":"https://ror.org/0220mzb33","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I183935753"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Aminah T Ali","raw_affiliation_strings":["King's College London"],"raw_orcid":"https://orcid.org/0000-0003-1089-9278","affiliations":[{"raw_affiliation_string":"King's College London","institution_ids":["https://openalex.org/I183935753"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161490153","display_name":"Ahmad Al Kheifat","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183935753","display_name":"King's College London","ror":"https://ror.org/0220mzb33","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I183935753"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Ahmad Al Kheifat","raw_affiliation_strings":["King's College London"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"King's College London","institution_ids":["https://openalex.org/I183935753"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5038119270","display_name":"Ammar Al\u2010Chalabi","orcid":"https://orcid.org/0000-0002-4924-7712","observed_orcids":["https://orcid.org/0000-0002-4924-7712"]},"institutions":[{"id":"https://openalex.org/I183935753","display_name":"King's College London","ror":"https://ror.org/0220mzb33","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I183935753"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Ammar Al-Chalabi","raw_affiliation_strings":["King's College London"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"King's College London","institution_ids":["https://openalex.org/I183935753"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073901666","display_name":"Alan Hodgkinson","orcid":"https://orcid.org/0000-0003-1636-491X","observed_orcids":["https://orcid.org/0000-0003-1636-491X"]},"institutions":[{"id":"https://openalex.org/I183935753","display_name":"King's College London","ror":"https://ror.org/0220mzb33","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I183935753"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Alan Hodgkinson","raw_affiliation_strings":["King's College London"],"raw_orcid":"https://orcid.org/0000-0003-1636-491X","affiliations":[{"raw_affiliation_string":"King's College London","institution_ids":["https://openalex.org/I183935753"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5013893534","display_name":"Alfredo Iacoangeli","orcid":"https://orcid.org/0000-0002-5280-5017","observed_orcids":["https://orcid.org/0000-0002-5280-5017"]},"institutions":[{"id":"https://openalex.org/I183935753","display_name":"King's College London","ror":"https://ror.org/0220mzb33","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I183935753"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Alfredo Iacoangeli","raw_affiliation_strings":["King's College London"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"King's College London","institution_ids":["https://openalex.org/I183935753"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5061885486"],"corresponding_institution_ids":["https://openalex.org/I183935753"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10855","display_name":"Amyotrophic Lateral Sclerosis Research","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10855","display_name":"Amyotrophic Lateral Sclerosis Research","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10301","display_name":"Mitochondrial Function and Pathology","score":0.000699999975040555,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.7639999985694885},{"id":"https://openalex.org/C2780596555","wikidata":"https://www.wikidata.org/wiki/Q206901","display_name":"Amyotrophic lateral sclerosis","level":3,"score":0.7634999752044678},{"id":"https://openalex.org/C24586158","wikidata":"https://www.wikidata.org/wiki/Q27075","display_name":"Mitochondrial DNA","level":3,"score":0.6815999746322632},{"id":"https://openalex.org/C28859421","wikidata":"https://www.wikidata.org/wiki/Q39572","display_name":"Mitochondrion","level":2,"score":0.595300018787384},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5526000261306763},{"id":"https://openalex.org/C151994961","wikidata":"https://www.wikidata.org/wiki/Q715263","display_name":"Human mitochondrial genetics","level":4,"score":0.5426999926567078},{"id":"https://openalex.org/C106208931","wikidata":"https://www.wikidata.org/wiki/Q1098876","display_name":"Genome-wide association study","level":5,"score":0.5141000151634216},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.49709999561309814},{"id":"https://openalex.org/C163950672","wikidata":"https://www.wikidata.org/wiki/Q14905375","display_name":"mitochondrial fusion","level":4,"score":0.4352000057697296},{"id":"https://openalex.org/C2777614518","wikidata":"https://www.wikidata.org/wiki/Q935710","display_name":"Mitochondrial disease","level":4,"score":0.4059000015258789},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.3693999946117401},{"id":"https://openalex.org/C111491248","wikidata":"https://www.wikidata.org/wiki/Q18033821","display_name":"DNAJA3","level":5,"score":0.3580999970436096},{"id":"https://openalex.org/C2777092462","wikidata":"https://www.wikidata.org/wiki/Q15334407","display_name":"MFN2","level":5,"score":0.3531999886035919},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.3522000014781952},{"id":"https://openalex.org/C141231307","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genome","level":3,"score":0.3357999920845032},{"id":"https://openalex.org/C2776925932","wikidata":"https://www.wikidata.org/wiki/Q1755122","display_name":"Neurodegeneration","level":3,"score":0.28769999742507935},{"id":"https://openalex.org/C2775833069","wikidata":"https://www.wikidata.org/wiki/Q6881881","display_name":"Mitochondrial myopathy","level":4,"score":0.2806999981403351},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.27869999408721924},{"id":"https://openalex.org/C102568066","wikidata":"https://www.wikidata.org/wiki/Q6718329","display_name":"MT-RNR1","level":4,"score":0.271699994802475},{"id":"https://openalex.org/C181561989","wikidata":"https://www.wikidata.org/wiki/Q2581905","display_name":"Heteroplasmy","level":4,"score":0.26919999718666077},{"id":"https://openalex.org/C9927688","wikidata":"https://www.wikidata.org/wiki/Q4915012","display_name":"Biological pathway","level":4,"score":0.2662000060081482},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.25920000672340393}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.11.10.764216","doi":"https://doi.org/10.64898/2026.11.10.764216","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.10.764216","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.11.10.764216","doi":"https://doi.org/10.64898/2026.11.10.764216","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.10.764216","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Mitochondrial":[0],"dysfunction":[1],"is":[2,19,68,417],"implicated":[3],"in":[4,46,57,205,225,230,242,261,265,286,299,322,329,353,371,374,378,421,435,453],"amyotrophic":[5],"lateral":[6],"sclerosis":[7],"(ALS),":[8],"but":[9],"which":[10,43,426],"mitochondrial":[11,33,66,165,169,254,274,362,401],"pathways":[12,36,73],"are":[13,37,44,463],"involved,":[14],"and":[15,59,65,82,92,101,111,123,132,158,195,214,221,244,278,325,446,459],"whether":[16,31,49,60,456],"their":[17],"involvement":[18],"a":[20,23,270,396,429],"cause":[21],"or":[22,438],"consequence":[24],"of":[25,76,105,410],"disease":[26],"remains":[27,465],"unclear.":[28],"We":[29,70],"investigated":[30],"nuclear-encoded":[32,361],"gene":[34,143,148,404,442],"(NEMG)":[35],"enriched":[38,173,282],"for":[39,74,174,208],"ALS":[40,47,77,86,130,175,231,262,287,372,393,423],"genetic":[41,78],"risk,":[42],"dysregulated":[45],"tissue,":[48,253],"pathway":[50,99,186,346],"activity":[51],"defines":[52],"patient":[53],"subgroups":[54],"that":[55],"differ":[56],"survival,":[58],"co-expression":[61,160],"between":[62],"the":[63,83,103,168,188,196,279,387,441],"nuclear":[64],"genomes":[67],"altered.":[69],"tested":[71],"MitoCarta3.0":[72],"enrichment":[75,145,241,398],"risk":[79,176,394,458],"using":[80,95,108],"MAGMA":[81],"largest":[84],"European":[85],"GWAS":[87],"to":[88,190,250,431],"date":[89],"(27,205":[90],"cases":[91],"110,881":[93],"controls),":[94],"hierarchical":[96],"testing":[97,183],"across":[98,273],"tiers,":[100],"annotated":[102],"direction":[104,226],"gene-level":[106],"effects":[107],"published":[109],"TWAS":[110],"SMR":[112],"results.":[113],"In":[114,252,356,390],">1,500":[115],"bulk":[116],"RNA-seq":[117],"samples":[118],"from":[119],"post-mortem":[120,359],"motor":[121,134,263,289,301,323,384,424],"cortex":[122,264,290],"spinal":[124,309,331,380],"cord":[125,310,332],"(KCL":[126],"Brain":[127],"Bank,":[128],"NYGC":[129],"Consortium)":[131],"iPSC-derived":[133,300,383],"neurones":[135,302,385],"(Answer":[136],"ALS),":[137],"we":[138],"performed":[139],"cell":[140,436],"type":[141],"adjusted":[142,354],"set":[144,149],"analysis":[146,151],"(GSEA),":[147],"variation":[150],"(GSVA)-based":[152],"clustering":[153],"with":[154,218,227,320,327,349,368,403],"exploratory":[155],"survival":[156,328,350],"analysis,":[157],"nuclear-mitochondrial":[159],"analysis.":[161],"Of":[162],"seven":[163],"broad":[164],"categories,":[166],"only":[167],"central":[170],"dogma":[171],"was":[172,247,342,347],"after":[177,351],"correction":[178,352],"(Padj":[179,192,198],"=":[180,193,199,293,304,337],"0.044).":[181],"Hierarchical":[182],"within":[184],"this":[185,284],"localised":[187],"signal":[189],"translation":[191],"0.008)":[194],"mitoribosome":[197,280],"0.014).":[200],"Genetically":[201],"predicted":[202,445],"expression":[203,217,229,448],"pointed":[204],"opposite":[206,388],"directions":[207,409],"different":[209],"mitoribosomal":[210],"genes":[211,255,363,370],"(lower":[212],"MRPS33":[213],"higher":[215],"MRPL28":[216],"increased":[219],"risk),":[220],"did":[222,450],"not":[223,451],"agree":[224,452],"differential":[228],"tissue":[232,461],"more":[233,258,365,418],"often":[234],"than":[235,373,407],"expected":[236],"by":[237],"chance.":[238],"A":[239],"nominal":[240],"ROS":[243],"glutathione":[245],"metabolism":[246],"largely":[248,268],"attributable":[249],"SOD1.":[251],"were":[256,281,296,318,364],"broadly":[257],"highly":[259,419],"expressed":[260,420],"both":[266],"cohorts,":[267],"as":[269,295],"global":[271],"shift":[272,285],"genes.":[275],"OXPHOS":[276,297],"subunits":[277,298],"beyond":[283],"Consortium":[288],"(both":[291],"PFDR":[292],"0.027),":[294],"(PFDR":[303],"2.4":[305],"x":[306],"10\u207b\u2078),":[307],"whereas":[308,382],"showed":[311,386],"no":[312],"genome-wide":[313],"enrichment.":[314],"GSVA":[315],"based":[316],"clusters":[317],"associated":[319,348],"diagnosis":[321],"cortex,":[324,425],"nominally":[326],"lumbar":[330,379],"(adjusted":[333],"HR":[334],"0.69,":[335],"Punadj":[336],"0.013),":[338],"where":[339],"cluster":[340],"structure":[341],"weakest.":[343],"No":[344],"individual":[345],"models.":[355],"all":[357],"four":[358],"tissues,":[360],"negatively":[366],"co-expressed":[367],"mtDNA-encoded":[369],"controls,":[375],"most":[376],"strongly":[377],"cord,":[381],"pattern.":[389],"conclusion,":[391],"inherited":[392,457],"shows":[395],"modest":[397],"centred":[399],"on":[400],"translation,":[402],"specific":[405],"rather":[406],"uniform":[408],"effect.":[411],"The":[412],"same":[413],"pathway,":[414],"alongside":[415],"OXPHOS,":[416],"end-stage":[422],"may":[427],"reflect":[428],"response":[430],"disease,":[432],"residual":[433],"differences":[434],"composition,":[437],"both.":[439],"At":[440],"level,":[443],"genetically":[444],"observed":[447],"changes":[449,462],"direction,":[454],"so":[455],"these":[460],"linked":[464],"unresolved.":[466]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}