Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3

Nat Genet. 2012 Sep;44(9):1026-9. doi: 10.1038/ng.2367. Epub 2012 Aug 5.


Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of thyrotoxicosis. We conducted a genome-wide association study (GWAS) and a replication study with a total of 123 southern Chinese with TPP (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; P(meta-analysis) = 1.8 × 10(-14)). All subjects with TPP also had Graves' disease, and subsequent TPP versus Graves' disease comparison confirmed that the association at 17q24.3 was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk prediction of TPP in subjects with Graves' disease was 0.73. Expression quantitative trait locus (eQTL) analysis identified SNPs in the region flanking rs312691 (±10 kb) that could potentially affect KCNJ2 expression (P = 0.0001). Our study has identified a susceptibility locus associated with TPP and provides insight into the causes of TPP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics
  • Chromosomes, Human, Pair 17 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Paralyses, Familial Periodic / ethnology
  • Paralyses, Familial Periodic / etiology
  • Paralyses, Familial Periodic / genetics*
  • Polymorphism, Single Nucleotide / physiology
  • Potassium Channels, Inwardly Rectifying / genetics
  • Quantitative Trait Loci* / genetics
  • Quantitative Trait Loci* / physiology
  • Thyrotoxicosis / complications
  • Thyrotoxicosis / ethnology
  • Thyrotoxicosis / genetics*


  • KCNJ16 protein, human
  • KCNJ2 protein, human
  • Potassium Channels, Inwardly Rectifying