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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.
Iacoangeli, Alfredo; Lin, Tian; Al Khleifat, Ahmad; Jones, Ashley R; Opie-Martin, Sarah; Coleman, Jonathan R I; Shatunov, Aleksey; Sproviero, William; Williams, Kelly L; Garton, Fleur; Restuadi, Restuadi; Henders, Anjali K; Mather, Karen A; Needham, Merilee; Mathers, Susan; Nicholson, Garth A; Rowe, Dominic B; Henderson, Robert; McCombe, Pamela A; Pamphlett, Roger; Blair, Ian P; Schultz, David; Sachdev, Perminder S; Newhouse, Stephen J; Proitsi, Petroula; Fogh, Isabella; Ngo, Shyuan T; Dobson, Richard J B; Wray, Naomi R; Steyn, Frederik J; Al-Chalabi, Ammar.
Affiliation
  • Iacoangeli A; Department of Biostatistics and Health Informatics, King's College London, London, UK; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK; National Institute for Health Research Biomedical Research Centre and Dementia Unit a
  • Lin T; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Brisbane QLD 4072, Australia.
  • Al Khleifat A; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK.
  • Jones AR; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK.
  • Opie-Martin S; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK.
  • Coleman JRI; National Institute for Health Research Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and King's College London, London, UK; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College Lon
  • Shatunov A; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK.
  • Sproviero W; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK.
  • Williams KL; Centre for Motor Neuron Disease Research, Macquarie University, Sidney NSW 2109, Australia.
  • Garton F; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Brisbane QLD 4072, Australia.
  • Restuadi R; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Brisbane QLD 4072, Australia.
  • Henders AK; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Brisbane QLD 4072, Australia.
  • Mather KA; Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney NSW, Australia; Neuroscience Research Australia, Randwick NSW, Australia.
  • Needham M; Fiona Stanley Hospital, 11 Robin Warren Drive, Murdoch Perth WA 6150, Australia; Notre Dame University, 32 Mouat Street, Fremantle WA 6160, Australia; Murdoch University, 90 South Street, Murdoch WA 6150, Australia.
  • Mathers S; Calvary Health Care Bethlehem, Parkdale VIC 3195, Australia.
  • Nicholson GA; ANZAC Research Institute, Concord Repatriation General Hospital, Sydney NSW 2139, Australia.
  • Rowe DB; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
  • Henderson R; Centre for Clinical Research, The University of Queensland, Brisbane QLD, Australia; Queensland Brain Institute, The University of Queensland, Brisbane QLD, Australia.
  • McCombe PA; Centre for Clinical Research, The University of Queensland, Brisbane QLD, Australia; Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane QLD, Australia.
  • Pamphlett R; Brain and Mind Centre, The University of Sydney, Sydney NSW, Australia.
  • Blair IP; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
  • Schultz D; Flinders Medical Centre, Bedford Park SA 5042, Australia.
  • Sachdev PS; Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney NSW, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney NSW Australia.
  • Newhouse SJ; Department of Biostatistics and Health Informatics, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and King's College London, London, UK; Institute of Health Informatics, Univers
  • Proitsi P; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK.
  • Fogh I; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
  • Ngo ST; Centre for Clinical Research, The University of Queensland, Brisbane QLD, Australia; Queensland Brain Institute, The University of Queensland, Brisbane QLD, Australia; Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane QLD, Australia; Australian Institute for Bioengineering and N
  • Dobson RJB; Department of Biostatistics and Health Informatics, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and King's College London, London, UK; Institute of Health Informatics, Univers
  • Wray NR; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Brisbane QLD 4072, Australia; Queensland Brain Institute, The University of Queensland, Brisbane QLD, Australia.
  • Steyn FJ; Centre for Clinical Research, The University of Queensland, Brisbane QLD, Australia; Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane QLD, Australia; School of Biomedical Sciences, The University of Queensland, Brisbane QLD, Australia.
  • Al-Chalabi A; Maurice Wohl Clinical Neuroscience Institute, King's College London, Department of Basic and Clinical Neuroscience, London, UK; King's College Hospital, Bessemer Road, London SE5 9RS, UK.
Cell Rep ; 33(4): 108323, 2020 10 27.
Article in En | MEDLINE | ID: mdl-33113361
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Acyltransferases / Weight Loss / Polymorphism, Single Nucleotide / Genome-Wide Association Study / Amyotrophic Lateral Sclerosis Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Cell Rep Year: 2020 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Acyltransferases / Weight Loss / Polymorphism, Single Nucleotide / Genome-Wide Association Study / Amyotrophic Lateral Sclerosis Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Cell Rep Year: 2020 Type: Article