Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study
Abstract High cortisol production in Cushing’s syndrome leads to fat centralisation. The influence of modest cortisol variations on body shape, however, is less clear. We examined potentially causal associations between morning plasma cortisol and body shape and obesity with inverse-variance weighte...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-53727-4 |
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| author | Sofia Christakoudi Alexandros-Georgios Asimakopoulos Elio Riboli Konstantinos K. Tsilidis |
| author_facet | Sofia Christakoudi Alexandros-Georgios Asimakopoulos Elio Riboli Konstantinos K. Tsilidis |
| author_sort | Sofia Christakoudi |
| collection | DOAJ |
| description | Abstract High cortisol production in Cushing’s syndrome leads to fat centralisation. The influence of modest cortisol variations on body shape, however, is less clear. We examined potentially causal associations between morning plasma cortisol and body shape and obesity with inverse-variance weighted random-effects models in a two-sample Mendelian randomisation analysis. We used publicly available summary statistics from the CORtisol NETwork (CORNET) consortium, UK Biobank, and the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Only in women, morning plasma cortisol (proxied by ten genetic polymorphisms) was associated positively with waist size reflected in waist-to-hip index (WHI, 0.035 standard deviation (SD) units change per one SD cortisol increase; 95% confidence interval (0.002–0.067); p = 0.036) and “a body shape index” (ABSI; 0.039 (0.006–0.071); p = 0.021). There was no evidence for associations with hip index (HI) or body mass index (BMI). Among individual polymorphisms, rs7450600 stood out (chromosome 6; Long Intergenic Non-Protein-Coding RNA 473 gene, LINC00473). Morning plasma cortisol proxied by rs7450600 was associated positively with WHI and inversely with HI and BMI in women and men. Our findings support a causal association of higher morning plasma cortisol with larger waist size in women and highlight LINC00473 as a genetic link between morning plasma cortisol and body shape. |
| first_indexed | 2024-03-07T15:09:27Z |
| format | Article |
| id | doaj.art-bec18a372f6c4383ac949c35351c68f8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:09:27Z |
| publishDate | 2024-02-01 |
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| series | Scientific Reports |
| spelling | doaj.art-bec18a372f6c4383ac949c35351c68f82024-03-05T18:44:25ZengNature PortfolioScientific Reports2045-23222024-02-0114111410.1038/s41598-024-53727-4Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation studySofia Christakoudi0Alexandros-Georgios Asimakopoulos1Elio Riboli2Konstantinos K. Tsilidis3Department of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Hygiene and Epidemiology, University of Ioannina School of MedicineDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonAbstract High cortisol production in Cushing’s syndrome leads to fat centralisation. The influence of modest cortisol variations on body shape, however, is less clear. We examined potentially causal associations between morning plasma cortisol and body shape and obesity with inverse-variance weighted random-effects models in a two-sample Mendelian randomisation analysis. We used publicly available summary statistics from the CORtisol NETwork (CORNET) consortium, UK Biobank, and the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Only in women, morning plasma cortisol (proxied by ten genetic polymorphisms) was associated positively with waist size reflected in waist-to-hip index (WHI, 0.035 standard deviation (SD) units change per one SD cortisol increase; 95% confidence interval (0.002–0.067); p = 0.036) and “a body shape index” (ABSI; 0.039 (0.006–0.071); p = 0.021). There was no evidence for associations with hip index (HI) or body mass index (BMI). Among individual polymorphisms, rs7450600 stood out (chromosome 6; Long Intergenic Non-Protein-Coding RNA 473 gene, LINC00473). Morning plasma cortisol proxied by rs7450600 was associated positively with WHI and inversely with HI and BMI in women and men. Our findings support a causal association of higher morning plasma cortisol with larger waist size in women and highlight LINC00473 as a genetic link between morning plasma cortisol and body shape.https://doi.org/10.1038/s41598-024-53727-4CortisolBody shapeObesityMendelian randomisation |
| spellingShingle | Sofia Christakoudi Alexandros-Georgios Asimakopoulos Elio Riboli Konstantinos K. Tsilidis Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study Scientific Reports Cortisol Body shape Obesity Mendelian randomisation |
| title | Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study |
| title_full | Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study |
| title_fullStr | Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study |
| title_full_unstemmed | Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study |
| title_short | Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study |
| title_sort | links between the genetic determinants of morning plasma cortisol and body shape a two sample mendelian randomisation study |
| topic | Cortisol Body shape Obesity Mendelian randomisation |
| url | https://doi.org/10.1038/s41598-024-53727-4 |
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