Soto-Pedre E, Siddiqui M, Mordi I, et al. - In large populations, electronic medical records linked to genomic data allow replication of genome-wide association study discoveries without additional genotyping costs. The outcomes illustrated that genetically raised serum thyroid-stimulating hormone (TSH) concentrations are causally correlated with reduced bone fracture risk in men.

• According to the findings, replication in 9,452 euthyroid individuals confirmed known loci previously reported.

• The results showed that 58 polymorphisms accounted for 11.08% of the TSH variation (p < 1e−04).

• It was shown that TSH-GRS was directly correlated 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).

• Furthermore, MR analysis of 5,599 individuals demonstrated that in comparison 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 found in women (OR = 0.93, p = 0.61).

• In addition,sensitivity analysis yielded similar outcomes.