ArticleJournal of human genetics2021
Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease.
Article in Journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Plasma cortisol-linked gene networks in hepatic and adipose tissues implicate corticosteroid-binding globulin in modulating tissue glucocorticoid action and cardiovascular risk.Frontiers in endocrinology · 2023Pooled it
- Effects of bogus genetic feedback on subjective and physiological responses to acute stress.Comprehensive psychoneuroendocrinology · 2026Article
- Biomarker for craving and acamprosate treatment response in patients with alcohol use disorder: insights from multi-omics.Molecular psychiatry · 2026Article
- Article
- Sex differences in clinical and metabolic outcomes of glucocorticoid replacement therapy in adrenal insufficiency.Pituitary · 2026Review
- Shared biological pathways linking ADHD and cortisol variability are related to externalizing behaviors.Psychoneuroendocrinology · 2025Article
- [Factors and conditions affecting transcortin production and function in blood plasma].Problemy endokrinologii · 2025Review
- Genome-wide association and fine-mapping analyses identify novel candidate genes affecting serum cortisol levels using imputed whole-genome sequencing data in pigs.Journal of animal science and technology · 2025Article
- Improving Cardiovascular Health Through the Consideration of Social Factors in Genetics and Genomics Research: A Scientific Statement From the American Heart Association.Circulation. Cardiovascular quality and outcomes · 2025Review
- Neuroinflammation-A Crucial Factor in the Pathophysiology of Depression-A Comprehensive Review.Biomolecules · 2025Review
- Prenatal maternal stress: triangulating evidence for intrauterine exposure effects on birth and early childhood outcomes across multiple approaches.BMC medicine · 2025Article
- The NE/AAT/CBG axis regulates adipose tissue glucocorticoid exposure.Nature communications · 2025Article
- A genetic exploration of the relationship between posttraumatic stress disorder and cardiovascular diseases.Translational psychiatry · 2025Article
- The Interaction of Polygenic Susceptibility to Stress and Childhood Adversity Dimensions Predicts Longitudinal Trajectories of Stress-Sensitivity.Stress and health : journal of the International Society for the Investigation of Stress · 2024Article
- Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.ERJ open research · 2024Article
- New insights into the hypothalamic-pituitary-thyroid axis: a transcriptome- and proteome-wide association study.European thyroid journal · 2024Article
- Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.medRxiv : the preprint server for health sciences · 2024Article
- Assessing the Role of Cortisol in Anxiety, Major Depression, and Neuroticism: A Mendelian Randomization Study UsingBiological psychiatry global open science · 2024Article
- A genetic exploration of the relationship between Posttraumatic Stress Disorder and cardiovascular diseases.medRxiv : the preprint server for health sciences · 2024Article
- Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
41 authors at 20 institutions in 11 countries.
Funding
Abstract
The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06-0.59) and myocardial infarction (0.21, 95% CI 0.00-0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.