The importance of high-quality mendelian randomisation studies for clinical thyroidology

Data from observational studies 1 Peeters RP Subclinical hypothyroidism. N Engl J Med. 2017; 376: 2556-2565 Crossref PubMed Scopus (131) Google Scholar , 2 Chaker L Cappola AR Mooijaart SP Peeters RP Clinical aspects of thyroid function during ageing. Lancet Diabetes Endocrinol. 2018; 6: 733-742 Summary Full Text Full Text PDF PubMed Scopus (39) Google Scholar have shown that subclinical thyroid disease—present in 5–10% of the population—and variations in thyroid function even within the reference range are associated with important health outcomes, including mortality, cardiovascular disease, dementia, and fractures. Although informative, these observational studies are susceptible to confounding, reverse causation, and other biases, which can lead to incorrect causal inference. 3 Grimes DA Schulz KF Bias and causal associations in observational research. Lancet. 2002; 359: 248-252 Summary Full Text Full Text PDF PubMed Scopus (920) Google Scholar Such incorrect inferences are unveiled when observational associations with disease risk are tested in randomised controlled trials and these trials do not find the anticipated health benefits. 4 Haycock PC Burgess S Wade KH Bowden J Relton C Davey Smith G Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies. Am J Clin Nutr. 2016; 103: 965-978 Crossref PubMed Scopus (239) Google Scholar The potential effect of these biases on observational study results should be considered in relation to the issue of whether subclinical thyroid dysfunction should be treated and the question of whether current thyroid reference ranges should be narrowed. Both questions are being intensively debated by the medical community. Correction to Lancet Diabetes Endocrinol 2019; 7: 665–67Medici M, Peeters RP, Teumer A, Taylor P. The importance of high-quality mendelian randomisation studies for clinical thyroidology. Lancet Diabetes Endocrinol 2019; 7: 665–67—In this comment author Robin Peeters's name (initials RP) has been corrected to Robin P Peeters (initials RPP). This correction has been made to the online version as of Aug 20, 2019 and the printed article is correct. Full-Text PDF