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Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases

Chen, Y. H. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Department of Human Genetics, McGill University, QC, Montreal, Canada
Lu, T. Y. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Quantitative Life Sciences Program, McGill University, QC, Montreal, Canada; 5 Prime Sciences Inc, QC, Montreal, Canada
Pettersson-Kymmer, Ulrika (author)
Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)
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Stewart, I. D. (author)
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
Butler-Laporte, G. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, QC, Montreal, Canada
Nakanishi, T. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Department of Human Genetics, McGill University, QC, Montreal, Canada; Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Japan Society for the Promotion of Science, Tokyo, Japan
Cerani, A. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, QC, Montreal, Canada
Liang, K. Y. H. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Quantitative Life Sciences Program, McGill University, QC, Montreal, Canada
Yoshiji, S. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Department of Human Genetics, McGill University, QC, Montreal, Canada; Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Japan Society for the Promotion of Science, Tokyo, Japan
Willett, J. D. S. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Quantitative Life Sciences Program, McGill University, QC, Montreal, Canada; McGill Genome Centre, McGill University, QC, Montreal, Canada
Su, C. Y. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Department of Computer Science, McGill University, QC, Montreal, Canada
Raina, P. (author)
Department of Health Research Methods, Evidence, and Impact, McMaster University, ON, Hamilton, Canada; McMaster Institute for Research on Aging, McMaster University, ON, Hamilton, Canada
Greenwood, C. M. T. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Quantitative Life Sciences Program, McGill University, QC, Montreal, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, QC, Montreal, Canada; Gerald Bronfman Department of Oncology, McGill University, QC, Montreal, Canada
Farjoun, Y. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; 5 Prime Sciences Inc, QC, Montreal, Canada; The Broad Institute of Harvard and MIT, MA, Cambridge, United States; Fulcrum Genomics, CO, Boulder, United States
Forgetta, V. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; 5 Prime Sciences Inc, QC, Montreal, Canada
Langenberg, C. (author)
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; Precision Healthcare University Research Institute, Queen Mary University of London, London, United Kingdom; Computational Medicine, Berlin Institute of Health (BIH) at Charité—Universitätsmedizin Berlin, Berlin, Germany
Zhou, S. R. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Department of Human Genetics, McGill University, QC, Montreal, Canada
Ohlsson, Claes, 1965 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Sahlgrenska Osteoporosis Centre, Centre of Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
Richards, J. B. (author)
Lady Davis Institute for Medical Research, Jewish General Hospital, QC, Montreal, Canada; Department of Human Genetics, McGill University, QC, Montreal, Canada; 5 Prime Sciences Inc, QC, Montreal, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, QC, Montreal, Canada; Department of Medicine, McGill University, QC, Montreal, Canada; Department of Twin Research, King’s College London, London, United Kingdom
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 (creator_code:org_t)
2023-01-12
2023
English.
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 55, s. 44-53
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, alpha-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Keyword

mendelian randomization
genetic-variation
wide association
rare
variants
identification
loci
discovery
health
Genetics & Heredity

Publication and Content Type

ref (subject category)
art (subject category)

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