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Identification of new genetic loci and environmental factors associated with parathyroid hormone levels.

Introduction: Parathyroid glands control calcium levels in blood through parathyroid hormone (PTH) regulation. Variations in PTH levels are under genetic control and influenced by environmental factors. The aim of this study was to identify genetic variants and environmental factors underlying parathyroid function by studying PTH levels in healthy individuals. To our knowledge, this is the first study that examines PTH using genome-wide data. Methods: PTH was measured in blood plasma of 1012 participants from Split, Croatia (aged 18- 85). To identify variants associated with PTH, genome-wide association study was performed using linear regression analysis and an additive model, with adjustments for age, gender and relatedness. To assess the influence of various environmental factors on PTH, nonparametric tests were used due to non-normal distribution of PTH levels. Results: We identified two potentially associated loci: rs28524851 on chromosome 22 in FAM19A5 gene (p=5.06*10-7, β=-0.33, SE=0.06) and rs6688219 on chromosome 1 in CASZ1 gene (p=7.96*10-7, β=-0.94, SE=0.19). Among females, PTH showed positive association with BMI and systolic blood pressure while smoking and alcohol consumption were negatively associated. Diastolic blood pressure was positively associated with PTH among males. Serum calcium levels and bone density showed negative association with PTH. Conclusions: We found two potentially associated loci that need to be confirmed in a replication study. One of those is located in CASZ1 gene which is known to be associated with cardiac phenotypes. These results also indicate that environmental factors have influence on parathyroid function.

Genome-wide association analysis ; Meta-analysis ; Parathyroid hormone

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