Author Correction: GWAS of thyroid stimulating hormone highlights the pleiotropic effects and inverse association with thyroid cancer.
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ABSTRACT:
SUBMITTER: Zhou W
PROVIDER: S-EPMC8677795 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Author Correction: GWAS of thyroid stimulating hormone highlights the pleiotropic effects and inverse association with thyroid cancer.
Zhou Wei W Brumpton Ben B Kabil Omer O Gudmundsson Julius J Thorleifsson Gudmar G Weinstock Josh J Zawistowski Matthew M Nielsen Jonas B JB Chaker Layal L Medici Marco M Teumer Alexander A Naitza Silvia S Sanna Serena S Schultheiss Ulla T UT Cappola Anne A Karjalainen Juha J Kurki Mitja M Oneka Morgan M Taylor Peter P Fritsche Lars G LG Graham Sarah E SE Wolford Brooke N BN Overton William W Rasheed Humaira H Haug Eirin B EB Gabrielsen Maiken E ME Skogholt Anne Heidi AH Surakka Ida I Davey Smith George G Pandit Anita A Roychowdhury Tanmoy T Hornsby Whitney E WE Jonasson Jon G JG Senter Leigha L Liyanarachchi Sandya S Ringel Matthew D MD Xu Li L Kiemeney Lambertus A LA He Huiling H Netea-Maier Romana T RT Mayordomo Jose I JI Plantinga Theo S TS Hrafnkelsson Jon J Hjartarson Hannes H Sturgis Erich M EM Palotie Aarno A Daly Mark M Citterio Cintia E CE Arvan Peter P Brummett Chad M CM Boehnke Michael M de la Chapelle Albert A Stefansson Kari K Hveem Kristian K Willer Cristen J CJ Åsvold Bjørn Olav BO
Nature communications 20211216 1
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Project description:Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors.
| S-EPMC7414135 | biostudies-literature
Project description:Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.
| S-EPMC10593800 | biostudies-literature
Project description:BackgroundThe relationship between normal thyroid-stimulating hormone (TSH) levels and thyroid disease in adults remains controversial. This study aimed to investigate the correlation between serum TSH levels, particularly those falling within the normal range, and thyroid diseases in Chinese adults, including thyroid nodules (TN), goiter (GR), and thyroid antibody positivity.Materials and methodsThis research was a cross-sectional study conducted in an adult population in Tianjin, China. Thyroid volume (Tvol) and TN were assessed using thyroid ultrasonography. Fasting venous blood and spot urine samples were collected to evaluate thyroid function and iodine status.ResultsA total of 2460 subjects participated in the survey. The prevalence of thyroid dysfunction was 9.76%, and abnormal TSH levels were found to potentially increase the risk of GR and thyroid antibody positivity in adults. A total of 2220 subjects with TSH within the normal reference range were included in the further study. In these patients, Tvol decreased as TSH levels increased, in both men and women (P < 0.0001). Low TSH levels (0.27-1.41 IU/mL) were identified as a risk factor for TN (odds ratio [OR], 1.46; 95% CI: 1.14-1.87) and GR (OR 5.90, 95% CI 2.27-15.3). Upon stratification by sex and age, the risk of TN was found to be higher in women and elderly individuals (≥60 years old), while the risk of GR was found to be higher in men and younger individuals (<60 years old). High TSH levels (2.55-4.2 IU/mL) were identified as a risk factor for thyroid antibody positivity (OR, 1.53; 95% CI: 1.11-2.10). Men and younger individuals with high TSH levels exhibited a higher risk of thyroid antibody positivity.ConclusionIn adults with normal TSH levels, low TSH levels were associated with an increased risk of TN and GR, whereas high TSH levels were associated with thyroid antibody positivity. The research also suggests that adults whose TSH levels at upper or lower limits of the normal range should be reviewed regularly.
| S-EPMC10577406 | biostudies-literature
Project description:High thyroid stimulating hormone (TSH) levels may stimulate papillary thyroid cancer (PTC) cell proliferation; however, the relationship between TSH levels and PTC risk remains controversial. We aim to ascertain the association through a meta-analysis. Literature searches were conducted in PubMed, Embase, and Web of Science databases. After literature screening, the methodological quality was assessed using the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality methods. Cochran's Q and I 2 tests were used to evaluate heterogeneity in the meta-analysis. Egger's test was applied to assess publication bias. A total of 12 eligible studies were included in this meta-analysis; all were of moderate and high methodological quality. The pooled results suggested that increased TSH levels were significantly associated with PTC risk; however, the included studies were significantly heterogeneous. Stratification analysis indicated that the heterogeneity might be from the area or type of control. Although significant publication bias existed among the studies, the trim-and-fill method and sensitivity analysis revealed that the combined results were stable and robust. TSH levels are significantly associated with the PTC risk; however, more high-quality studies in large sample sizes are recommended to verify the extrapolation of these findings.
| S-EPMC10426723 | biostudies-literature
Project description:BackgroundNormal brain development is dependent on maternal, fetal and neonatal thyroid function. Measuring neonatal thyroid-stimulating hormone (TSH) 48-72 hours after birth screens for congenital hypothyroidism, allowing early treatment to avoid serious impairment. However, even within sub-clinical ranges, disrupted thyroid homeostasis during brain development has been linked to adverse neurodevelopmental outcomes, including attention-deficit/hyperactivity disorder (ADHD).ObjectivesTo estimate the association between neonatal TSH below threshold for potential congenital hypothyroidism and subsequent ADHD diagnosis using a population-based birth cohort.MethodsChildren with a diagnosis of ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa) were identified through linkage with the Norwegian Patient Registry using ICD-10 codes for hyperkinetic disorders. The study included 405 ADHD cases and 1,092 controls (born 2003-2008) with available neonatal TSH concentrations below 10 mU/L (cut-off for potential congenital hypothyroidism) measured in dried blood spots sampled 48-72 hours after birth.ResultsIn multivariable, quintile models the relationship appeared to follow a U-shaped pattern with elevated odds ratios (OR) at lower and higher TSH levels. Among children with TSH in the lowest quintile, odds of ADHD was approximately 1.5-fold higher than children in the middle quintile (OR 1.60, 95% CI 1.09, 2.34), which was driven by substantially elevated risk among girls, with no association among boys (Pinteraction = 0.02; girls OR 3.10, 95% CI 1.53, 6.30; boys OR 1.16, 95% CI 0.73, 1.84).ConclusionsADHD risk appeared to be elevated among newborns with low TSH levels (i.e. with hyperthyroid status), and this association was mainly found among girls. Because our findings are suggestive of increased risk at very low TSH concentrations, where analytical accuracy is low, future studies should employ highly sensitive assays capable of accurate quantitation at very low concentrations. Also, larger studies are needed to investigate these associations at higher neonatal TSH concentrations where data are more widely distributed.
| S-EPMC7431377 | biostudies-literature
Project description:High serum thyroid-stimulating hormone (TSH) levels are linked to many metabolic disorders, but the effects of TSH levels on the oral microbiota are still largely unknown. This study aimed to explore the association between the salivary microbiome in adults and serum TSH levels. Saliva and fasting blood samples were obtained from a health census conducted in Southeast China. All participants were divided according to serum TSH levels. The microbial genetic profiles and changes were acquired by 16S rDNA sequencing and bioinformatics analysis. Relevant anthropometric and biochemical measurements such as insulin resistance, blood lipids, and body composition were evaluated with laboratory tests and physical examinations. The salivary microbiome in individuals with higher TSH level showed significantly higher taxa diversity. Principal coordinates analysis and partial least squares discriminant analysis showed distinct clustering in the Abnormal and Normal Groups (Adonis, P=0.0320). Granulicatella was identified as a discriminative genus for comparison of the two groups. Fasting serum insulin, Homeostatic Model Assessment for Insulin Resistance, and hemoglobin A1 were elevated in the Abnormal Group (P<0.05), showing the presence of insulin resistance in individuals with abnormal higher serum TSH levels. Distance-based redundancy analysis revealed the association of this distinctive difference with salivary microbiome. In conclusion, shifts in microbial profile were observed in the saliva of individuals with different serum TSH levels, and insulin resistance may play an important role in the biochemical and microbial alteration.
| S-EPMC7952758 | biostudies-literature
Project description:ObjectiveTo investigate the association between thyroid-stimulating hormone (TSH) and clinically relevant depression (CRD) in a population-based study.Patients and methodsAdult patients (≥18 years of age) who received care at Mayo Clinic in Rochester, Minnesota, and completed a TSH and Patient Health Questionnaire - 9 (PHQ-9) within 6 months of each other, between July 8, 2017, and August 31, 2021, were included. Demographics, medical comorbidities, thyroid function laboratory data, psychotropic medications, presence of primary thyroid disorder, thyroid hormone replacement (T4 and/or T3), and mood disorder diagnoses (using International Classification of Diseases, 10th version, Clinical Modifications codes) were extracted electronically. The primary outcome, CRD, was defined as a PHQ-9 score greater than or equal to 10. Logistic regression analysis was conducted to assess the association between TSH categories (low ≤0.3 mIU/L; normal >0.3-4.2 mIU/L; high >4.2 mIU/L) and CRD.ResultsThe cohort included 29,034 patients, mean age 51.4 years, 65% females, 89.9% White, and a mean body mass index of 29.9 kg/m2. The mean ± standard deviation for TSH was 3.0±8.5 mIU/L, and the mean PHQ-9 score was 6.3±6.2. After adjustment, the odds of CRD were significantly higher among the low TSH category (odds ratio, 1.37; 95% CI, 1.18-1.57; P<.001) compared with the normal TSH category, especially in people 70 years of age or younger compared with people older than 70 years of age. Subgroup analysis did not show an increase in odds of CRD among patients with subclinical/overt hypothyroidism/hyperthyroidism (after adjustment).ConclusionIn this large population-based cross-sectional study, we report that low TSH was associated with higher odds of depression. Future longitudinal cohort studies are needed to investigate the relationship between thyroid dysfunction and depression as well as sex differences.
| S-EPMC10554405 | biostudies-literature
Project description:BackgroundOvert thyroid dysfunction has been associated with adverse obstetric outcomes. However, less is known regarding subclinical hypothyroidism or thyroid autoimmunity and their relationship to pregnancy complications.ObjectiveThe purpose of this study was to examine the association between prepregnancy anti-thyroid antibodies and subclinical hypothyroidism and preterm delivery, gestational diabetes mellitus, and preeclampsia.Study designWe conducted a secondary analysis of a prospective cohort of 18- to 40-year-old women with 1-2 previous pregnancy losses (n=1193) who participated in a multicenter randomized, placebo-controlled trial of low-dose aspirin. Prepregnancy levels of thyroid-stimulating hormone, free thyroxine, thyroglobulin antibody, and thyroid peroxidase antibody were measured. Relative risks and 95% confidence intervals were estimated with the use of generalized linear models with adjustment for age and body mass index.ResultsAmong women with an ongoing pregnancy of >20 weeks estimated gestational age, there was no association between prepregnancy thyroid-stimulating hormone level (>2.5 vs ≤2.5 mIU/L) and preterm delivery (adjusted relative risk, 0.77; 95% confidence interval, 0.40-1.47), gestational diabetes mellitus (adjusted relative risk, 1.28; 95% confidence interval, 0.54-3.04), or preeclampsia (adjusted relative risk, 1.20; 95% confidence interval, 0.71-2.04). Similarly, among women with thyroid antibodies, there was no increase in the likelihood of preterm delivery (relative risk, 1.26; 95% confidence interval, 0.65-2.45), gestational diabetes mellitus (relative risk, 1.33; 95% confidence interval, 0.51-3.49), or preeclampsia (relative risk, 1.02; 95% confidence interval, 0.54-1.92), compared with women without these antibodies.ConclusionAmong women with 1-2 previous pregnancy losses, subclinical hypothyroidism and thyroid autoimmunity were not associated with an increased risk of preterm delivery, gestational diabetes mellitus, or preeclampsia. These data support current recommendations that low-risk asymptomatic women should not be screened routinely for thyroid dysfunction or autoimmunity.
| S-EPMC5712235 | biostudies-literature
Project description: Not available
| S-EPMC10784491 | biostudies-literature
Project description:Human thyroid stimulating hormone (TSH) is a glycoprotein secreted by the anterior part of the pituitary gland. TSH plays an important physiological role in the regulation of hypothalamic-pituitary-thyroid axis by modulating the release of the thyroid hormones from the thyroid gland. It induces iodine uptake by the thyroid, promotes thyroid epithelial differentiation and growth, and protects thyroid cells from apoptosis. Impairment of TSH signal transduction pathway leads to thyroid disorders such as goitre, hypothyroidism and hyperthyroidism, which can have complex clinical manifestations. TSH signaling is largely effected through two separate pathways, the adenylate cyclase and the phospholipase C pathways. In spite of its biomedical importance, a concise signaling map of TSH pathway is not available in the public domain. Therefore, we have generated a detailed signaling map of TSH pathway by systematically cataloging the molecular reactions induced by TSH including protein-protein interactions, post-translational modifications, protein translocation events and activation/inhibition reactions. We have cataloged 40 molecular association events, 42 enzyme-substrate reactions and 16 protein translocation events in TSH signaling pathway resource. Additionally, we have documented 208 genes, which are differentially regulated by TSH. We have provided the details of TSH pathway through NetPath (http://www.netpath.org), which is a publicly available resource for human signaling pathways developed by our group. We have also depicted the map of TSH signaling using NetSlim criteria (http://www.netpath.org/netslim/) and provided pathway maps in Wikipathways (http://www.wikipathways.org/). We anticipate that the availability of TSH pathway as a community resource will enhance further biomedical investigations into the function and effects of this important hormone.
| S-EPMC3830942 | biostudies-literature