A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis
Abstract
Several lines of evidence have pointed out that genetic components have roles in thyrotoxic hypokalemic periodic paralysis (TTPP). In this study, for the first time we performed genome-wide association study (GWAS) in male hyperthyroid subjects in order to identify genetic loci conferring susceptibility to TTPP. We genotyped 78 Thai male TTPP cases and 74 Thai male hyperthyroid patients without hypokalemia as controls with Illumina Human-Hap610 Genotyping BeadChip. Among the SNPs analyzed in the GWAS, rs312729 at chromosome 17q revealed the lowest P-value for association (P=2.09 × 10(-7)). After fine mapping for linkage disequilibrium blocks surrounding the landmark SNP, we found a significant association of rs623011; located at 75 kb downstream of KCNJ2 on chromosome 17q, reached the GWAS significance after Bonferroni's adjustment (P=3.23 × 10(-8), odds ratio (OR)=6.72; 95% confidence interval (CI)=3.11-14.5). The result was confirmed in an independent cohort of samples consisting of 28 TTPP patients and 48 controls using the same clinical criteria diagnosis (replication analysis P=3.44 × 10(-5), OR=5.13; 95% CI=1.87-14.1; combined-analysis P=3.71 × 10(-12), OR=5.47; 95% CI=3.04-9.83).
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- Authors
- Jongjaroenprasert, W., Phusantisampan, T., Mahasirimongkol, S., Mushiroda, T., Hirankarn, N., Snabboon, T., Chanprasertyotin, S., Tantiwong, P., Soonthornpun, S., Rattanapichart, P., Mamanasiri, S., Himathongkam, T., Ongphiphadhanakul, B., Takahashi, A., Kamatani, N., Kubo, M., & Nakamura, Y.
- Affiliations
- Mahidol University (TH)
- Prince of Songkla University (TH)
- Ministry of Public Health (TH)
- RIKEN (JP)
- Chulalongkorn University (TH)
- Maharat Nakhon Ratchasima Hospital (TH)
- Sappasithiprasong Hospital (TH)
- Ratchaburi Hospital (TH)
- The University of Tokyo (JP)
- Corresponding author
- Jongjaroenprasert, Wallaya
- ORCID
- Venue
- Journal of Human Genetics
- Published
- 2012-03-08
- Volume
- 57
- Issue
- 5
- Pages
- 301-304
- ISSN
- 1434-5161 (ISSN-L)
- 1435-232X
- OpenAlex
- W1991985767
- Cited by
- 33
- References
- 22
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 2 · 2012: 4
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Thailand Research Fund
- RIKEN
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- thyrotoxic hypokalemic periodic paralysis, hyperthyroidism, genetic susceptibility, KCNJ2, chromosome 17q, single nucleotide polymorphisms, linkage disequilibrium, fine mapping, replication study, Thai men
- MeSH terms
- Chromosomes, Human, Pair 17, Genotype, Humans, Hyperthyroidism, Male, Thailand, Genetic Variation, Linkage Disequilibrium, Case-Control Studies, Genetic Predisposition to Disease, Paralysis, Hyperkalemic Periodic, Polymorphism, Single Nucleotide, Potassium Channels, Inwardly Rectifying, Asian People, Genome-Wide Association Study
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