{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:02:01Z","timestamp":1770422521788,"version":"3.49.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206046\/Z\/17\/Z"],"award-info":[{"award-number":["206046\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000761","name":"Imperial College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000761","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u00a0UK Biobank participants (117\u00a0944, 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\u2013293 genes associated with serum amino acids, including MIP,\u00a0GLS2, SLC\u00a0gene family, GCKR, LMO1, CPS1\u00a0and COBLL1.The gene\u2013property 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\u00a0analysis 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\u00a0with higher levels of total cholesterol, triglyceride and\u00a0low-density lipoprotein, and lower levels of\u00a0high-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\u2019s disease, breast cancer\u00a0or 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.<\/jats:p>","DOI":"10.1093\/nargab\/lqae046","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T10:54:37Z","timestamp":1714992877000},"source":"Crossref","is-referenced-by-count":3,"title":["Unravelling genetic architecture of circulatory amino acid levels, and their effect on risk of complex disorders"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8089-7150","authenticated-orcid":false,"given":"Leila","family":"Abar","sequence":"first","affiliation":[{"name":"Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary\u2019s Campus , Norfolk Place, London W2 1PG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-1877","authenticated-orcid":false,"given":"Verena","family":"Zuber","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary\u2019s Campus , Norfolk Place, London W2 1PG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg W","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary\u2019s Campus , Norfolk Place, London W2 1PG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-9328","authenticated-orcid":false,"given":"Ioanna","family":"Tzoulaki","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary\u2019s Campus , Norfolk Place, London W2 1PG , UK"},{"name":"Centre for Systems Biology, Biomedical Research Foundation Academy of Athens , 115 27\u00a0Athens, Greece"},{"name":"BHF Centre of Excellence,\u00a0School of Public Health, Imperial College London , London W2 1PG , UK"},{"name":"UK Dementia Research Institute, Imperial College London , London W12 0BZ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbas","family":"Dehghan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary\u2019s Campus , Norfolk Place, London W2 1PG , UK"},{"name":"BHF Centre of Excellence,\u00a0School of Public Health, Imperial College London , London W2 1PG , UK"},{"name":"UK Dementia Research Institute, Imperial College London , London W12 0BZ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"2024050610541941500_B1","doi-asserted-by":"crossref","first-page":"954","DOI":"10.3390\/ijms19040954","article-title":"Branched chain amino acids: beyond nutrition metabolism","volume":"19","author":"Nie","year":"2018","journal-title":"Int. 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