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Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease.
Cadby, Gemma; Giles, Corey; Melton, Phillip E; Huynh, Kevin; Mellett, Natalie A; Duong, Thy; Nguyen, Anh; Cinel, Michelle; Smith, Alex; Olshansky, Gavriel; Wang, Tingting; Brozynska, Marta; Inouye, Mike; McCarthy, Nina S; Ariff, Amir; Hung, Joseph; Hui, Jennie; Beilby, John; Dubé, Marie-Pierre; Watts, Gerald F; Shah, Sonia; Wray, Naomi R; Lim, Wei Ling Florence; Chatterjee, Pratishtha; Martins, Ian; Laws, Simon M; Porter, Tenielle; Vacher, Michael; Bush, Ashley I; Rowe, Christopher C; Villemagne, Victor L; Ames, David; Masters, Colin L; Taddei, Kevin; Arnold, Matthias; Kastenmüller, Gabi; Nho, Kwangsik; Saykin, Andrew J; Han, Xianlin; Kaddurah-Daouk, Rima; Martins, Ralph N; Blangero, John; Meikle, Peter J; Moses, Eric K.
Afiliación
  • Cadby G; School of Population and Global Health, University of Western Australia, Crawley, WA, Australia.
  • Giles C; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Melton PE; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia.
  • Huynh K; School of Population and Global Health, University of Western Australia, Crawley, WA, Australia.
  • Mellett NA; Menzies Research Institute, University of Tasmania, Hobart, TAS, Australia.
  • Duong T; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Nguyen A; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia.
  • Cinel M; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Smith A; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Olshansky G; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Wang T; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Brozynska M; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Inouye M; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • McCarthy NS; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia.
  • Ariff A; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Hung J; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia.
  • Hui J; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Beilby J; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Dubé MP; School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia.
  • Watts GF; School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
  • Shah S; School of Medicine, The University of Western Australia, Crawley, WA, Australia.
  • Wray NR; Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.
  • Lim WLF; Busselton Population Medical Research Institute Inc., Perth, WA, Australia.
  • Chatterjee P; Busselton Population Medical Research Institute Inc., Perth, WA, Australia.
  • Martins I; PathWest Laboratory Medicine WA, Perth, WA, Australia.
  • Laws SM; Busselton Population Medical Research Institute Inc., Perth, WA, Australia.
  • Porter T; PathWest Laboratory Medicine WA, Perth, WA, Australia.
  • Vacher M; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Montreal, QC, Canada.
  • Bush AI; School of Medicine, The University of Western Australia, Crawley, WA, Australia.
  • Rowe CC; Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, WA, Australia.
  • Villemagne VL; Institute for Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia.
  • Ames D; Institute for Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia.
  • Masters CL; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
  • Taddei K; School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
  • Arnold M; Cooperative research Centre (CRC) for Mental Health, Joondalup, WA, Australia.
  • Kastenmüller G; School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
  • Nho K; Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
  • Saykin AJ; KaRa Institute of Neurological Disease, Sydney, Macquarie Park, NSW, Australia.
  • Han X; School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
  • Kaddurah-Daouk R; Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
  • Martins RN; Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
  • Blangero J; Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
  • Meikle PJ; Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
  • Moses EK; Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Nat Commun ; 13(1): 3124, 2022 06 06.
Article en En | MEDLINE | ID: mdl-35668104
ABSTRACT
We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P < 1 × 10-3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria Tipo de estudio: Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Australia
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria Tipo de estudio: Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Australia