Genetic variants associated with circulating parathyroid hormone

Cassianne Robinson-Cohen, Pamela L. Lutsey, Marcus E. Kleber, Carrie M. Nielson, Braxton D. Mitchell, Joshua C. Bis, Karen M. Eny, Laura Portas, Joel Eriksson, Mattias Lorentzon, Daniel L. Koller, Yuri Milaneschi, Alexander Teumer, Stefan Pilz, Maria Nethander, Elizabeth Selvin, Weihong Tang, Lu Chen Weng, Hoi Suen Wong, Dongbing LaiMunro Peacock, Anke Hannemann, Uwe Völker, Georg Homuth, Matthias Nauk, Federico Murgia, Jack W. Pattee, Eric Orwoll, Joseph M. Zmuda, Jose Antonio Riancho, Myles Wolf, Frances Williams, Brenda Penninx, Michael J. Econs, Kathleen A. Ryan, Claes Ohlsson, Andrew D. Paterson, Bruce M. Psaty, David S. Siscovick, Jerome I. Rotter, Mario Pirastu, Elizabeth Streeten, Winfried März, Caroline Fox, Josef Coresh, Henri Wallaschofski, James S. Pankow, Ian H. De Boer, Bryan Kestenbaum

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


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=4.2310-53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of theminor allele at this SNP associatedwith 7%higher serum PTHconcentration. The other SNPs associatedwith serum PTH concentration included rs4074995 within RGS14 (P=6.6 3 10-17), rs219779 adjacent to CLDN14 (P=3.5310-16), rs4443100 nearRTDR1 (P=8.7310-9), and rs73186030 nearCASR(P=4.8310-8). 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.

Original languageEnglish (US)
Pages (from-to)1553-1565
Number of pages13
JournalJournal of the American Society of Nephrology
Issue number5
StatePublished - May 2017

ASJC Scopus subject areas

  • General Medicine


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