A genome- and phenome-wide association study of plasma procalcitonin concentrations in individuals of European ancestry
Abstract
Background: Procalcitonin (PCT) is a biomarker used to differentiate between viral and bacterial infections, though the underlying mechanisms are not yet fully understood. This study aimed to identify genetic variants associated with plasma PCT concentrations and explore the associations of genetically predicted PCT with a wide range of disease related traits in a PheWAS.
Methods: We conducted GWAS and meta-analysis using data from the MDCS (n = 4007), MPP (n = 5097), and PREVEND (n = 3344) cohorts. We used fine-mapping to prioritise likely causal variants and explored regulatory effects using eQTL data, summary-data-based Mendelian randomisation (SMR) and colocalisation. To validate the PCT findings, we conducted multi-trait analysis of GWAS (MTAG) combining our results with CALCA data from a large pQTL study. The polygenic risk score (PRS) for PCT was calculated in the UK Biobank (n = 457,418) based on the GWAS summary data, and associations between the PRS and 179 traits were assessed in a PheWAS.
Findings: We identified four independent significant SNPs in three loci associated with plasma PCT: CALCB (rs7119706, rs10832337), PBX4 (rs17217098), and PRDM15 (rs7277773). Fine-mapping prioritised 18 likely causal variants, including rs7119706 (near CALCB) and rs16930609 (mapped to CYP2R1) at the chromosome 11 locus. Our eQTL lookup identified significant results for 13 genes, but SMR and colocalisation analyses did not support their potentially causal effects on plasma PCT.…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 457,418 participants or records.
Read the paper
Related studies
- Effectiveness of Bisphosphonates and Denosumab on Risk of Vertebral Fractures in Prostate Cancer Patients Under Androgen Deprivation Therapies: A Real-World Prospective Study
- Osteoporosis-related fractures after spinal cord injury: a retrospective study from Brazil
- Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men
- Lack of Association between Vitamin D Insufficiency and Cardiovascular or Fracture Risk: A UK Biobank Study
- Muscle strength and body composition are clinical indicators of osteoporosis
- Incidence of bone protection and associated fragility injuries in patients with proximal femur fractures
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.