SynthesisPLoS genetics2012
A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
Synthesis in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 3 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.
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Who cites it
103 citing papers in PubMed, 3 syntheses or guidelines pooled it, 255 citations in OpenAlex.
- Genetic and observational evidence supports a causal role of sex hormones on the development of asthma.Thorax · 2019Pooled it
- Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero.Human molecular genetics · 2018Pooled it
- Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies.PLoS genetics · 2016Pooled it
- Genetic Variation in Steroid and Xenobiotic Metabolizing Pathways and Enterolactone Excretion Before and After Flaxseed Intervention in African American and European American Women.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Trial
- Identification of MEF2A, MEF2C, and MEF2D interactomes in basal and Fsk-stimulated mouse MA-10 Leydig cells.Andrology · 2026Article
- The association between androgenic profile and cardiometabolic risk factors in young men: insights from a large observational cohort study.Journal of endocrinological investigation · 2026Article
- Polymorphic Variant Associated with Sex Hormone-Binding Globulin Level Is a Risk Factor for Preeclampsia.International journal of molecular sciences · 2026Article
- BMI-Dependent Associations of the Estradiol-Linked Polymorphism rs117585797 of theLife (Basel, Switzerland) · 2026Article
- FGF21 and SHBG as Putative Hepatic Axes in Maternal Metabolic Adaptation: A Hypothetical Framework for Postpartum Insulin Sensitivity Restoration.Biomolecules · 2026Review
- Multi-omics profiles of sex hormone-binding globulin are associated with subclinical atherosclerosis in men with HIV.Genome medicine · 2026Article
- Gene Polymorphisms Determining Sex Hormone-Binding Globulin Levels and Endometriosis Risk.International journal of molecular sciences · 2025Article
- Obesity/Overweight as a Meaningful Modifier of Associations Between Gene Polymorphisms Affecting the Sex Hormone-Binding Globulin Content and Uterine Myoma.Life (Basel, Switzerland) · 2025Article
- Local genetic sex differences in quantitative traits.Nature communications · 2025Article
- Mendelian randomization study reveals the causal effect of sex hormone binding globulin on osteoporosis.BMC musculoskeletal disorders · 2025Article
- Sex Hormone-Binding Globulin and Metabolic Syndrome in Children and Adolescents: A Focus on Puberty.Metabolites · 2025Review
- Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk.Life (Basel, Switzerland) · 2025Article
- Phenotypes Associated With Polycystic Ovary Syndrome Risk Variants.Journal of the Endocrine Society · 2024Article
- Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study.Scientific reports · 2024Article
- Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study.Research square · 2024Article
- Obesity-Dependent Association of the rs10454142Biomedicines · 2024Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
99 authors at 20 institutions in 9 countries.
Funding
Abstract
Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11)), GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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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.