Journal article
Genome-wide Meta-analysis finds the ACSL5-ZDHHC6 locus Is associated with ALS and links weight loss to the disease genetics
Cell Reports, Vol.33(4), Art. 108323
2020
Abstract
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. 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.
Details
- Title
- Genome-wide Meta-analysis finds the ACSL5-ZDHHC6 locus Is associated with ALS and links weight loss to the disease genetics
- Authors/Creators
- A. Iacoangeli (Author/Creator)T. Lin (Author/Creator)A. Al Khleifat (Author/Creator)A.R. Jones (Author/Creator)S. Opie-Martin (Author/Creator)J.R.I. Coleman (Author/Creator)A. Shatunov (Author/Creator)W. Sproviero (Author/Creator)K.L. Williams (Author/Creator)F. Garton (Author/Creator)R. Restuadi (Author/Creator)A.K. Henders (Author/Creator)K.A. Mather (Author/Creator)M. Needham (Author/Creator)S. Mathers (Author/Creator)G. Nicholson (Author/Creator)D.B. Rowe (Author/Creator)R. Henderson (Author/Creator)P.A. McCombe (Author/Creator)R. Pamphlett (Author/Creator)I.P. Blair (Author/Creator)D. Schultz (Author/Creator)P.S. Sachdev (Author/Creator)S.J. Newhouse (Author/Creator)P. Proitsi (Author/Creator)I. Fogh (Author/Creator)S.T. Ngo (Author/Creator)R.J.B. Dobson (Author/Creator)N.R. Wray (Author/Creator)F.J. Steyn (Author/Creator)A. Al-Chalabi (Author/Creator)
- Publication Details
- Cell Reports, Vol.33(4), Art. 108323
- Publisher
- Elsevier Inc.
- Identifiers
- 991005543878107891
- Copyright
- © 2020 The Author(s).
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.765 ALS Mechanisms
- Web Of Science research areas
- Cell Biology
- ESI research areas
- Molecular Biology & Genetics