biostudies-literatureIacoangeli AEconomic and Social Research CouncilGuy's and St Thomas' CharitySpastic Paraplegia FoundationMotor Neurone Disease AssociationMND ScotlandGuy's and St Thomas' NHS Foundation TrustEU Joint Programme – Neurodegenerative Disease ResearchMotor Neurone Disease Research Institute of AustraliaMedical Research CouncilHorizon 2020National Institute for Health Research (NIHR)National Health and Medical Research CouncilMaudsley CharityWellcome Trust108323https://www.ebi.ac.uk/biostudies/studies/S-EPMC7610013biostudies-literatureUnknown33(4)We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10^-9), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. Cell reportsGenome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics.PMC7610013Iacoangeli/Apr19/869-791MC_PC_17214ALCHALABI-TALBOT/APR14/926-794HDR-2007HDR-9004MR/L501529/1HDR-9002HDR-9003AL-CHALABI/APR15/844-791ES/L008238/1G0600974ALCHALABI-DOBSON/APR14/829-791MR/R024804/1CS-2018-18-ST2-014Wray NRLin TColeman JRISachdev PSMathers SMcCombe PAHenderson RFogh IWilliams KLGarton FDobson RJBPamphlett RBlair IPNeedham MRestuadi RHenders AKSchultz DSteyn FJShatunov AIacoangeli ANgo STMather KANicholson GAAl Khleifat AOpie-Martin SRowe DBSproviero WNewhouse SJAl-Chalabi AJones ARProitsi PfalseGenome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics.We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10^-9), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. 2020-01-01T00:00:00Z2020 Oct2026-05-03T08:09:59.088Z2025-05-29T22:20:26.488ZS-EPMC76100133311336110.1016/j.celrep.2020.108323