New insights into the hypothalamic–pituitary–thyroid axis: a transcriptome- and proteome-wide association study
Authors' conclusion
Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein levels relevant to thyroid function.
Study context
- Outcome
- Gene products related to TSH and FT4 levels
Methodological detailstissue-specific transcriptome-wide association studies (TWAS), plasma proteome-wide association studies (PWAS), genetic colocalization
- Tissue-specific TWAS
- Plasma PWAS
- Genetic colocalization
Main finding
As reported in the abstract
- TWAS: transcripts associated with TSH
- 297
- TWAS: transcripts associated with free thyroxine (FT4)
- 113
- TWAS: transcripts shared by TSH and FT4
- 25
- Transcripts colocalized with TSH
- 158
- Transcripts colocalized with FT4
- 45
- PWAS: proteins associated with TSH
- 18
- PWAS: proteins associated with FT4 (HEXIM1 and QSOX2 with both)
- 10
- TSH-associated proteins whose cognate genes mapped outside significant genome-wide association studies (GWAS) loci
- 5
- FT4-associated proteins whose cognate genes mapped outside significant GWAS loci
- 7
- Plasma proteins colocalized with TSH
- 5
- Plasma proteins colocalized with FT4
- 5
- TSH-related genes significant in both TWAS and PWAS
- 10
- FT4-related genes significant in both TWAS and PWAS
- 1
- Plasma annexin A5 inversely associated with TSH (PWAS)
- P = 1.18 × 10-13
- ANXA5 expression inversely associated with TSH, TWAS whole blood
- P = 7.61 × 10-12
- ANXA5 expression inversely associated with TSH, TWAS hypothalamus
- P = 6.40 × 10-13
- ANXA5 expression inversely associated with TSH, TWAS pituitary
- P = 1.57 × 10-15
- ANXA5 expression inversely associated with TSH, TWAS thyroid
- P = 4.27 × 10-15
Original publication
New insights into the hypothalamic–pituitary–thyroid axis: a transcriptome- and proteome-wide association study. Eur Thyroid J. Published 20 June 2024. doi:10.
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