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

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. Inte...

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Vydáno v:	Nature genetics Ročník 55; číslo 1; s. 44 - 53
Hlavní autoři:	Chen, Yiheng, Lu, Tianyuan, Pettersson-Kymmer, Ulrika, Stewart, Isobel D., Butler-Laporte, Guillaume, Nakanishi, Tomoko, Cerani, Agustin, Liang, Kevin Y. H., Yoshiji, Satoshi, Willett, Julian Daniel Sunday, Su, Chen-Yang, Raina, Parminder, Greenwood, Celia M. T., Farjoun, Yossi, Forgetta, Vincenzo, Langenberg, Claudia, Zhou, Sirui, Ohlsson, Claes, Richards, J. Brent
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.01.2023 Nature Publishing Group
Témata:	45 45/43 631/208/205/2138 631/45/320 692/699/249/1313 692/699/2743 692/699/2743/316/801 Aging Agriculture Alzheimer's disease Animal Genetics and Genomics Asthma Biomedical and Life Sciences Biomedicine Body mass index Body size Bone density Bone Density - genetics Bone mass Bone mineral density Cancer Research Cardiovascular disease Diabetes discovery Fractures Gene expression Gene Function genetic-variation Genetics & Heredity Genome-wide association studies Genome-Wide Association Study Genomes Genomics health Health risks Human Genetics Humans identification Inflammatory bowel disease Inflammatory bowel diseases Influence Lipids loci Medical Genetics and Genomics Medicinsk genetik och genomik mendelian randomization Metabolism Metabolites Metabolome - genetics Phenotype Polymorphism, Single Nucleotide - genetics rare Ratios Therapeutic applications Therapeutic targets variants wide association
ISSN:	1061-4036, 1546-1718, 1546-1718
On-line přístup:	Získat plný text
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Shrnutí:	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, α-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. Genome-wide association studies comprising 1,091 metabolites and 309 metabolite ratios in 8,299 individuals from the Canadian Longitudinal Study on Aging provide insights into the genetic architecture of metabolites and their role in human diseases.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/s41588-022-01270-1