Towards Personalized Thyroid-stimulating Hormone (TSH) Reference Ranges: A Genetic and Population-Based Approach in Three Independent Cohorts
Authors' conclusion
Individual genetic profiles have the potential to personalize TSH reference ranges, with large effects on reclassification of diagnosis and LT4 prescriptions.
Study context
- Population
- Thyroid disease-free population-based cohorts (n = 6,834; validation n = 3,800); third cohort without thyroid disease and on levothyroxine (LT4)three cohorts · third cohort without thyroid disease 26,321 · on LT4 1,132
- Exposure
- Genetically determined vs population-based TSH reference ranges
- Outcome
- Predictors of individual TSH concentrations and reclassification
Methodological detailsthree independent cohorts, polygenic score of 59 genetic variants, validation cohort
- Three independent cohorts
- Polygenic score of 59 genetic variants
- Validation cohort
Main finding
As reported in the abstract
Total variance in TSH explained by polygenic score (PGS)
9.2-11.1%
Total variance in TSH explained by FT4
2.4-2.7%
Total variance in TSH explained by any other nongenetic factor
0.2-1.8%
Subclinical hypo- and hyperthyroidism (population-based ranges) reclassified as euthyroid with genetically determined ranges
Up to 24.7-30.1%
Observational data: associations, not effects.
Further findings
LT4 prescription by PGS quartile · higher probability of LT4 in higher PGS quartiles
P for trend = 1.7 × 10-8
Original publication
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