Dataset Information

Evidence of a Causal Relationship between Serum Thyroid-Stimulating Hormone and Osteoporotic Bone Fractures.

ABSTRACT:

Objective

We aimed to validate the association of genome-wide association study (GWAS)-identified loci and polygenic risk score with serum thyroid-stimulating hormone (TSH) concentrations and the diagnosis of hypothyroidism. Then, the causal relationship between serum TSH and osteoporotic bone fracture risk was tested.

Methods

A cross-sectional study was done among patients of European Caucasian ethnicity recruited in Tayside (Scotland, UK). Electronic medical records (EMRs) were used to identify patients and average serum TSH concentration and linked to genetic biobank data. Genetic associations were performed by linear and logistic regression models. One-sample Mendelian randomization (MR) was used to test causality of serum TSH on bone fracture risk.

Results

Replication in 9,452 euthyroid individuals confirmed known loci previously reported. The 58 polymorphisms accounted for 11.08% of the TSH variation (p < 1e-04). TSH-GRS was directly associated with the risk of hypothyroidism with an odds ratio (OR) of 1.98 for the highest quartile compared to the first quartile (p = 2.2e-12). MR analysis of 5,599 individuals showed that compared with those in the lowest tertile of the TSH-GRS, men in the highest tertile had a decreased risk of osteoporotic bone fracture (OR = 0.59, p = 2.4e-03), while no difference in a similar comparison was observed in women (OR = 0.93, p = 0.61). Sensitivity analysis yielded similar results.

Conclusions

EMRs linked to genomic data in large populations allow replication of GWAS discoveries without additional genotyping costs. This study suggests that genetically raised serum TSH concentrations are causally associated with decreased bone fracture risk in men.

SUBMITTER: Soto-Pedre E

PROVIDER: S-EPMC8647109 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectivePrevious epidemiological studies have found an association between serum cholesterol level and bone mineral density. However, epidemiological studies evaluating the association between serum cholesterol level and the incidence of osteoporotic fracture are scant. Therefore, the objective of this study was to investigate whether serum cholesterol levels in Chinese participants aged 55?years or older was associated with an increased risk of osteoporotic fracture.Materials and methodsWe performed a cross-sectional study, including 1,791 participants (62.1% postmenopausal women and 213 fractures). Standardized self-administered questionnaires, physical examination, laboratory tests, and dual-energy X-ray absorptiometry examination were performed. Multivariate-adjusted logistic regression models were used to evaluate associations between serum cholesterol [total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C)] levels and the osteoporotic fracture risk.ResultsAfter adjusting for potential confounding factors, there were no associations between per SD increase in TC and LDL level and an increased risk of osteoporotic fracture in total participants, and in men and women as individual groups. There was a significant association between per SD increase in HDL-C level and an increased risk of osteoporotic fracture in total participants [odds ratios (OR) 1.20, 95% confidence interval (CI) 1.03, 1.40, P?=?0.023] and in women (OR 1.37, 95% CI 1.12, 1.68, P?=?0.003), whereas no association was observed in men (OR 1.01, 95% CI 0.73, 1.40, P?=?0.951). Additionally, we found a significant association between per SD increase in TG level and an increased risk of osteoporotic fracture in total participants (OR 1.20, 95% CI 1.04, 1.38, P?=?0.015). In women, a nonlinear relationship was observed between per SD increase in TG level and an increased risk of osteoporotic fracture. The risk of osteoporotic fracture in women increased with TG level >1.64?mmol/L (OR 1.93, 95% CI 1.24, 3.00, P?=?0.004).ConclusionAmong Chinese older adults, serum HDL-C level is significantly associated with a risk of osteoporotic fractures in women, and serum TG level is significantly associated with a risk of osteoporotic fractures in total participants and in women with TG >1.64?mmol/L.

Project description:BACKGROUND:Overt 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. OBJECTIVE:The 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 DESIGN:We 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. RESULTS:Among 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. CONCLUSION:Among 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.