SynthesisPLoS genetics2014
Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.
Open access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 5 pooled it
7.7field-weighted citation impact, top 2% of its field
What it found
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The trial behind it
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Who cites it
78 citing papers in PubMed, 5 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- Genome-wide association and multi-omics analyses provide insights into the disease mechanisms of central serous chorioretinopathy.Scientific reports · 2025Pooled it
- 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
- Plasma Cortisol and Risk of Atrial Fibrillation: A Mendelian Randomization Study.The Journal of clinical endocrinology and metabolism · 2021Pooled it
- Morning plasma cortisol as a cardiovascular risk factor: findings from prospective cohort and Mendelian randomization studies.European journal of endocrinology · 2019Pooled it
- Pooled it
- Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes.Scientific reports · 2017Trial
- Biomarker for craving and acamprosate treatment response in patients with alcohol use disorder: insights from multi-omics.Molecular psychiatry · 2026Article
- Methylome and transcriptome analysis reveal the impact of psychological stress on the skin.Molecular genetics and genomics : MGG · 2026Article
- A single glucocorticoid response element regulates sociability in a sex-specific manner.Molecular psychiatry · 2026Article
- Shared biological pathways linking ADHD and cortisol variability are related to externalizing behaviors.Psychoneuroendocrinology · 2025Article
- Unveiling the Evolutionary History and Functional Significance of the Protein Z-Dependent Protease Inhibitor (ZPI) Across Vertebrates.Journal of molecular evolution · 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
- Genetic Correlates of Treatment-Resistant Depression.JAMA psychiatry · 2025Article
- Article
- Binding for life: corticosteroid binding globulin from vertebrate physiology to human diseases.Frontiers in endocrinology · 2025Review
- Morning cortisol as an indicator of arterial stiffness in patients with type 2 diabetes: prospective cohort study and Mendelian randomization study.Frontiers in endocrinology · 2025Article
- Facing stress and inflammation: From the cell to the planet.World journal of experimental medicine · 2024Review
- Current Challenges and Future Directions in the Assessment of Glucocorticoid Status.Endocrine reviews · 2024Review
- Testing the causal relationship of fat and sugar intake with depression and cortisol: a Mendelian Randomisation study.Translational psychiatry · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
57 authors at 20 institutions in 8 countries.
Jennifer L BoltonUniversity/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Caroline HaywardMRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Nese DirekDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
John G LewisCanterbury Health Laboratories, Christchurch, New Zealand.
Geoffrey L HammondDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
Lesley A HillDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
Anna AndersonUniversity/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Jennifer HuffmanMRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
James F WilsonCentre for Population Health Sciences, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Harry CampbellCentre for Population Health Sciences, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Igor RudanCentre for Population Health Sciences, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Alan WrightMRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Nicholas HastieMRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Sarah H WildCentre for Population Health Sciences, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Fleur P VeldersDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Albert HofmanDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Andre G UitterlindenDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Jari LahtiInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Katri RäikkönenInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Eero KajantieNational Institute for Health and Welfare, Helsinki, Finland.
Elisabeth WidenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Aarno PalotieInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
Johan G ErikssonNational Institute for Health and Welfare, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland; Folkhalsan Research Centre, Helsinki, Finland; Vasa Central Hospital, Vasa, Finland.
Marika KaakinenInstitute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland.
Marjo-Riitta JärvelinInstitute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland; Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland; Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, Imperial College London, London, United Kingdom; Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
Nicholas J TimpsonMRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
George Davey SmithMRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
Susan M RingSchool of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
David M EvansMRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
Beate St PourcainSchool of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
Toshiko TanakaLongitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
Yuri MilaneschiLongitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America; Department of Psychiatry, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
Stefania BandinelliGeriatric Unit, ASF, Florence, Italy.
Luigi FerrucciLongitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
Pim van der HarstUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
Judith G M RosmalenUniversity of Groningen, University Medical Center Groningen, Interdisciplinary Center for Psychiatric Epidemiology, Groningen, The Netherlands.
Stephen J L BakkerUniversity of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, The Netherlands.
Niek VerweijUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands.
Robin P F DullaartUniversity of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, The Netherlands.
Anubha MahajanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Cecilia M LindgrenWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Andrew MorrisWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Lars LindDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Erik IngelssonDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Laura N AndersonSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Craig E PennellSchool of Women's and Infant's Health, The University of Western Australia, Crawley, Australia.
Stephen J LyeSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Stephen G MatthewsDepartment of Physiology, University of Toronto, Toronto, Ontario, Canada.
Joel ErikssonCenter for Bone and Arthritis Research, Institute of Medicin, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Dan MellstromCenter for Bone and Arthritis Research, Institute of Medicin, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Claes OhlssonCenter for Bone and Arthritis Research, Institute of Medicin, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Jackie F PriceCentre for Population Health Sciences, Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Mark W J StrachanUniversity/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Rebecca M ReynoldsUniversity/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Henning TiemeierDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Brian R WalkerUniversity/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
CORtisol NETwork (CORNET) Consortium
University of Edinburgh · GBErasmus University Rotterdam · NLUniversity of Bristol · GBInstitute of Genetics and Cancer · GBUniversity of Helsinki · FICentre for Human Genetics · GBThe Queen's Medical Research Institute · GBUniversity Medical Center Groningen · NLUniversity of Gothenburg · SENational Institute on Aging · USUniversity of British Columbia · CAUniversity of Groningen · NLUniversity of Oulu · FIUppsala University · SECanterbury Health Laboratories · NZFinnish Institute for Health and Welfare · FIFolkhälsans Forskningscentrum · FIGGZ inGeest · NLLunenfeld-Tanenbaum Research Institute · CAMount Sinai Hospital · CA
Funding
The Aging Genome Association Study "AGE-GAIN"ZIAAG000965 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2025
$4.0MGenetics of cardiovascular risk factors in large founder population birth controlR01HL087679 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HIRSCHHORN, JOEL N · 2007 to 2009
$4.0MGenetic Influences on ADHD in a Finnish Birth CohortR01MH063706 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMALLEY, SUSAN L · 2001 to 2005
$3.3MWhole Genome Assoc. Analysis Strategies for Multi. PhenotypesRL1MH083268 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B. · 2007 to 2011
$2.1MBritish Heart Foundation RG/11/4/28734Chief Scientist Office CZB/4/710CIHR MOP82893Medical Research Council G0500539Medical Research Council G0500877Medical Research Council G0600705Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_U127561128Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/3Medical Research Council MC_UU_12013/4NHLBI NIH HHS R01 HL087679NIMH NIH HHS 1RL1MH083268-01NIMH NIH HHS 5R01MH63706:02NIMH NIH HHS R01 MH063706NIMH NIH HHS RL1 MH083268Wellcome Trust 090532Wellcome Trust 098017Wellcome Trust 102215Wellcome Trust WT064890
Abstract
Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
Indexed as
Genome-Wide Association StudyAdolescentAdultAgedAged, 80 and overalpha 1-AntitrypsinCohort StudiesExomeFemaleHumansHydrocortisoneMaleMiddle AgedMutationPolymorphism, Single NucleotideProtein Bindingalpha 1-AntitrypsinHydrocortisoneSERPINA1 protein, humanSERPINA6 protein, humanTranscortin
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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.