Unravelling genetic architecture of circulatory amino acid levels, and their effect on risk of complex disorders.

Autor:	Abar L; Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK., Zuber V; Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK., Otto GW; Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK., Tzoulaki I; Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.; Centre for Systems Biology, Biomedical Research Foundation Academy of Athens, 115 27 Athens, Greece.; BHF Centre of Excellence, School of Public Health, Imperial College London, London W2 1PG, UK.; UK Dementia Research Institute, Imperial College London, London W12 0BZ, UK., Dehghan A; Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.; BHF Centre of Excellence, School of Public Health, Imperial College London, London W2 1PG, UK.; UK Dementia Research Institute, Imperial College London, London W12 0BZ, UK.
Jazyk:	angličtina
Zdroj:	NAR genomics and bioinformatics [NAR Genom Bioinform] 2024 May 06; Vol. 6 (2), pp. lqae046. Date of Electronic Publication: 2024 May 06 (Print Publication: 2024).
DOI:	10.1093/nargab/lqae046
Abstrakt:	Variations in serum amino acid levels are linked to a multitude of complex disorders. We report the largest genome-wide association study (GWAS) on nine serum amino acids in the UK Biobank participants (117 944, European descent). We identified 34 genomic loci for circulatory levels of alanine, 48 loci for glutamine, 44 loci for glycine, 16 loci for histidine, 11 loci for isoleucine, 19 loci for leucine, 9 loci for phenylalanine, 32 loci for tyrosine and 20 loci for valine. Our gene-based analysis mapped 46-293 genes associated with serum amino acids, including MIP ,  GLS2 , SLC  gene family, GCKR , LMO1 , CPS1  and COBLL1 .The gene-property analysis across 30 tissues highlighted enriched expression of the identified genes in liver tissues for all studied amino acids, except for isoleucine and valine, in muscle tissues for serum alanine and glycine, in adrenal gland tissues for serum isoleucine and leucine, and in pancreatic tissues for serum phenylalanine. Mendelian randomization (MR) phenome-wide association study analysis and subsequent two-sample MR analysis provided evidence that every standard deviation increase in valine is associated with 35% higher risk of type 2 diabetes and elevated levels of serum alanine and branched-chain amino acids with higher levels of total cholesterol, triglyceride and low-density lipoprotein, and lower levels of high-density lipoprotein. In contrast to reports by observational studies, MR analysis did not support a causal association between studied amino acids and coronary artery disease, Alzheimer's disease, breast cancer or prostate cancer. In conclusion, we explored the genetic architecture of serum amino acids and provided evidence supporting a causal role of amino acids in cardiometabolic health. (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)
Databáze:	MEDLINE
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