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Depositordc.contributorCrawford, Andrew
Funderdc.contributor.otherBritish Heart Foundationen_UK
Funderdc.contributor.otherChief Scientist Office, Scottish Government
Data Creatordc.creatorWalker, Brian
Date Accessioneddc.date.accessioned2017-08-10T11:04:53Z
Date Availabledc.date.available2017-08-10T11:04:53Z
Citationdc.identifier.citationWalker, Brian. (2017). Summary GWAS data for morning plasma cortisol from the Cortisol Network (CORNET) Consortium 2014 (n=12,597), [dataset]. Cortisol Network (CORNET) Consortium. http://dx.doi.org/10.7488/ds/2113.en
Persistent Identifierdc.identifier.urihttp://hdl.handle.net/10283/2787
Persistent Identifierdc.identifier.urihttp://dx.doi.org/10.7488/ds/2113
Dataset Description (abstract)dc.description.abstractVariation 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.en_UK
Dataset Description (TOC)dc.description.tableofcontentsgwama_1_fixed.out: Morning plasma cortisol GWAS meta-analysis (n=12,597) README_CORNET.pdfen_UK
Languagedc.language.isoengen_UK
Publisherdc.publisherCortisol Network (CORNET) Consortiumen_UK
Relation (Is Referenced By)dc.relation.isreferencedbyhttps://doi.org/10.1371/journal.pgen.1004474en_UK
Subjectdc.subjectcortisolen_UK
Subjectdc.subjectSERPINA1en_UK
Subjectdc.subjectSERPINA6en_UK
Subjectdc.subjectstress hormoneen_UK
Subject Classificationdc.subject.classificationBiological Sciences::Human Geneticsen_UK
Titledc.titleSummary GWAS data for morning plasma cortisol from the Cortisol Network (CORNET) Consortium 2014 (n=12,597)en_UK
Alternative Titledc.title.alternativeGenome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulinen_UK
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