Genotype-first characterization of familial hypocalciuric hypercalcemia type 1: prevalence, serum calcium, and clinical associations
Authors' conclusion
Taken together, these data indicate that FHH1 is more common than previously appreciated and is characterized by variable degrees of hypercalcemia and modest hypophosphatemia, although biochemical characterization was limited by unavailable urinary calcium and parathyroid hormone data.
Study context
- Population
- UK Biobank participants with whole-exome/whole-genome sequencing data (454,787 exomes/490,640 genomes)454,787 exomes/490,640 genomes
- Exposure
- FHH1-associated CASR variant carriers vs remaining UK Biobank (UKB) population
- FHH1n = 162
- Outcome
- Prevalence of FHH1
Methodological detailsUK Biobank whole-exome/whole-genome sequencing linked to health records, PheWAS across ICD-10 diagnoses
- UK Biobank whole-exome/whole-genome sequencing linked to health records
- PheWAS across ICD-10 diagnoses
Main finding
As reported in the abstract
FHH1 prevalence (UKB)
FHH1
33.0/100,000
162 of 162
Observational data: associations, not effects.
Further findings
Serum calcium
P = 1.2×10-72
Serum phosphorus
P = 6.7×10-17
Serum calcium
- Serum calcium overlapped from ≈9.2-9.4 mg/dL upward
PheWAS clinical associations
- PheWAS signals dominated by calcium/parathyroid-related traits; pancreatitis- or diabetes-related outcomes did not meet multiple-testing-corrected significance thresholds
FHH1 prevalence from allele frequency (gnomAD v4.1)
- Overall prevalence (SE)
- 31.2(2.0)/100,000
- Admixed American group
- 46.6(12.5)/100,000
- Ashkenazi Jewish group
- 13.5(9.6)/100,000
- Varied by ancestry
Original publication
Genotype-first characterization of familial hypocalciuric hypercalcemia type 1: prevalence, serum calcium, and clinical associations. J Bone Miner Res. Published 25 August 2026. doi:10.
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