Genetic Variants Associated with Circulating Parathyroid Hormone.


Journal Article

Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10-53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10-17), rs219779 adjacent to CLDN14 (P=3.5 × 10-16), rs4443100 near RTDR1 (P=8.7 × 10-9), and rs73186030 near CASR (P=4.8 × 10-8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.

Full Text

Duke Authors

Cited Authors

  • Robinson-Cohen, C; Lutsey, PL; Kleber, ME; Nielson, CM; Mitchell, BD; Bis, JC; Eny, KM; Portas, L; Eriksson, J; Lorentzon, M; Koller, DL; Milaneschi, Y; Teumer, A; Pilz, S; Nethander, M; Selvin, E; Tang, W; Weng, L-C; Wong, HS; Lai, D; Peacock, M; Hannemann, A; Völker, U; Homuth, G; Nauk, M; Murgia, F; Pattee, JW; Orwoll, E; Zmuda, JM; Riancho, JA; Wolf, M; Williams, F; Penninx, B; Econs, MJ; Ryan, KA; Ohlsson, C; Paterson, AD; Psaty, BM; Siscovick, DS; Rotter, JI; Pirastu, M; Streeten, E; März, W; Fox, C; Coresh, J; Wallaschofski, H; Pankow, JS; de Boer, IH; Kestenbaum, B

Published Date

  • May 2017

Published In

Volume / Issue

  • 28 / 5

Start / End Page

  • 1553 - 1565

PubMed ID

  • 27927781

Pubmed Central ID

  • 27927781

Electronic International Standard Serial Number (EISSN)

  • 1533-3450

Digital Object Identifier (DOI)

  • 10.1681/ASN.2016010069


  • eng

Conference Location

  • United States