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Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics

Research output: Contribution to journalArticle

Original languageEnglish
JournalCell Reports
Published27 Oct 2020

King's Authors


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 3 109
), 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. In patients’
fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: 2.1
± 1.3 kg/A allele, p = 0.053; rs3828599: 1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics
to weight loss in patients.

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