SynthesisHuman molecular genetics2010
Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes.
Synthesis in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 8 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 8 syntheses or guidelines pooled it, 222 citations in OpenAlex.
- Endogenous Sex Steroid Hormones, Sex Hormone-Binding Globulin, and Risk of All-Cause and Cause-Specific Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.The Journal of clinical endocrinology and metabolism · 2025Pooled it
- Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.Clinical chemistry · 2023Pooled it
- Association of puberty timing with type 2 diabetes: A systematic review and meta-analysis.PLoS medicine · 2020Pooled it
- Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study.PLoS medicine · 2019Pooled it
- Pooled it
- A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.PLoS genetics · 2012Pooled it
- Genetic determinants of serum testosterone concentrations in men.PLoS genetics · 2011Pooled it
- Studies of the association of Arg72Pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 Europeans.PloS one · 2011Pooled it
- Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program.The Journal of clinical endocrinology and metabolism · 2015Trial
- Sex hormone binding globulin, but not testosterone, is associated with the metabolic syndrome in overweight and obese women with polycystic ovary syndrome.Journal of endocrinological investigation · 2013Trial
- Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men.PloS one · 2012Trial
- The impact of an aromatase inhibitor on body composition and gonadal hormone levels in women with breast cancer.Breast cancer research and treatment · 2011Trial
- Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women.Diabetes · 2011Trial
- Sex hormone-binding globulin and coronary heart disease: a narrative review of associations and biomarker potential.Journal of thoracic disease · 2026Review
- Sex steroids, SHBG and type 2 diabetes in women: what do we really know?Diabetologia · 2026Review
- SHBG, Testosterone, and Type 2 Diabetes Risk in Middle-Aged African Women: Exploring the Effect of HIV and Menopause.The Journal of clinical endocrinology and metabolism · 2025Observational
- Associations of 2923 Olink proteins with demographic, lifestyle, environmental and health characteristics in middle-aged Chinese adults.European journal of epidemiology · 2025Article
- Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study.Communications biology · 2025Article
- Sex Hormone-Binding Globulin and Metabolic Syndrome in Children and Adolescents: A Focus on Puberty.Metabolites · 2025Review
- Investigating the Mediating Role of Cardiometabolic Traits in the Causal Link Between SHBG Levels and Stroke Risk via Network Mendelian Randomization.Current issues in molecular biology · 2025Article
54 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
59 authors at 20 institutions in 8 countries.
Funding
Abstract
Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 x 10(-5)], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes.
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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 Socratic graph.