Genome-wide association study of plasma amino acids and Mendelian randomization for cardiometabolic traits
Plasma amino acids (AAs) have emerged as promising biomarkers for metabolic disorders, yet their causality remains unclear. We aimed to investigate the genetic determinants of AA levels in a cohort of 10,333 individuals and their causal effects on cardiometabolic traits using Mendelian randomization (MR). Plasma levels of 20 AAs were quantified using capillary electrophoresis mass spectrometry. Genome-wide association studies were conducted using BOLT-LMM and heritability estimation via LDSC analysis. Causal effects of AAs on 11 cardiometabolic traits were examined using two-sample MR analyses. We identified 85 locus-metabolite associations across 43 genes for 18 AAs, including 44 novel loci linked to metabolic genes. Heritability for AAs was estimated at 16%. MR analysis demonstrated cystine to positively associate with systolic blood pressure (SBP) (β = 0.056, SE = 0.010), while serine indicated protective effects on SBP (β = - 0.040, SE = 0.011), diastolic BP (β = - 0.044, SE = 0.010), and coronary artery disease (odds ratio 0.888, SE = 0.028). We identified potentially novel genetic loci associated with AA levels and demonstrated robust causal associations between several AAs and cardiometabolic traits. These findings reinforce the importance of AAs as potential biomarkers and therapeutic targets in cardiometabolic health.
Authors
- Aya Hirata (ORCID: https://orcid.org/0000-0003-1439-4242)
- Tomonori Okamura (ORCID: https://orcid.org/0000-0003-0488-0351)
- Masaru Tomita (ORCID: https://orcid.org/0000-0003-3423-377X)
- Kengo Kinoshita (ORCID: https://orcid.org/0000-0003-3453-2171)
- Atsushi Shimizu (ORCID: https://orcid.org/0000-0001-8307-2461)
- Miho Iida (ORCID: https://orcid.org/0000-0001-5527-7574)
- Shinji Fushiki (ORCID: https://orcid.org/0000-0002-0407-9954)
- Tomoyoshi Soga (ORCID: https://orcid.org/0000-0001-9502-2509)
- Yayoi Otsuka‐Yamasaki (ORCID: https://orcid.org/0000-0002-9464-0804)
- Akiyoshi Hirayama (ORCID: https://orcid.org/0000-0002-0440-6820)
- Mika Sakurai‐Yageta (ORCID: https://orcid.org/0000-0001-5606-3324)
- Toru Takebayashi (ORCID: https://orcid.org/0000-0002-8268-8026)
- Sei Harada (ORCID: https://orcid.org/0000-0003-2666-4932)
- Naoko Miyagawa (ORCID: https://orcid.org/0000-0002-9148-1078)
- Kazuharu Arakawa (ORCID: https://orcid.org/0000-0002-2893-4919)
- Masahiro Sugimoto (ORCID: https://orcid.org/0000-0003-3316-2543)
- Asako Sato (ORCID: https://orcid.org/0009-0007-3057-1313)
- Shun Kojima
- Hideki Ohmomo (ORCID: https://orcid.org/0000-0002-3524-6524)
- Gen Tamiya (ORCID: https://orcid.org/0000-0002-0597-415X)
- Minako Matsumoto (ORCID: https://orcid.org/0000-0002-7705-9903)
- Ryota Toki
- Shun Edagawa
- Atsuko Miyake (ORCID: https://orcid.org/0000-0003-1391-4576)
- Kaori Amano
- Yoichi Sutoh
- Kazuyo Kuwabara
Institutions
- Iwate Medical University (JP)
- Tohoku University (JP)
- Keio University (JP)
- RIKEN Center for Advanced Intelligence Project (JP)
- Tohoku Medical Megabank Organization (JP)
- Konica Minolta (Japan) (JP)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1038/s41598-025-98992-z
- Citations
- 2
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 3.63
Funders
- Japan Society for the Promotion of Science