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

Abstract

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; Pmeta-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.

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Figure 1: Regional association plot of the 17q24.3 locus.
Figure 2: Regional genome-wide association and KCNJ2 eQTL plot of the 17q24.3 locus.

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Acknowledgements

We are grateful to all study participants and investigators at the individual centers for taking part. We are extremely grateful to all investigators who contributed to the generation of this data set. P.-C.S. was supported by The University of Hong Kong Strategic Research Theme of Genomics.

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A.W.C.K. obtained financial support. A.W.C.K. and C.-L.C. designed the study. A.W.C.K., P.-C.S. and C.-L.C. designed and supervised data analyses. C.-L.C. performed data analyses. K.-S.L. managed and prepared DNA samples. A.Y.Y.H., K.-K.L., S.-C.T., E.Y.F.L., J.L., M.-W.T., K.-W.C., C.-Y.Y., Y.-C.W., E.Y.N.C., V.H.F.H., H.-K.P., C.-S.H. and A.W.C.K. ascertained and recruited samples. A.W.C.K. and C.-L.C. drafted the manuscript. A.W.C.K., P.-C.S. and C.-L.C. revised the manuscript. All authors critically reviewed and approved the manuscript.

Corresponding authors

Correspondence to Ching-Lung Cheung, Pak-Chung Sham or Annie W C Kung.

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The authors declare no competing financial interests.

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Cheung, CL., Lau, KS., Ho, A. et al. Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3. Nat Genet 44, 1026–1029 (2012). https://doi.org/10.1038/ng.2367

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