title: 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).
authors.affiliation: Endocrine and Metabolism Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Rama 6 Road, Mahidol University, Bangkok, Thailand. rawjj@mahidol.ac.th
authors.forename: Wallaya
authors.initials: W
authors.lastname: Jongjaroenprasert
authors.forename: Theerawut
authors.initials: T
authors.lastname: Phusantisampan
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.forename: Nattiya
authors.initials: N
authors.lastname: Hirankarn
authors.forename: Thiti
authors.initials: T
authors.lastname: Snabboon
authors.forename: Suwannee
authors.initials: S
authors.lastname: Chanprasertyotin
authors.forename: Puntip
authors.initials: P
authors.lastname: Tantiwong
authors.forename: Supamai
authors.initials: S
authors.lastname: Soonthornpun
authors.forename: Paninee
authors.initials: P
authors.lastname: Rattanapichart
authors.forename: Sunee
authors.initials: S
authors.lastname: Mamanasiri
authors.forename: Thep
authors.initials: T
authors.lastname: Himathongkam
authors.forename: Boonsong
authors.initials: B
authors.lastname: Ongphiphadhanakul
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006980:Hyperthyroidism / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020513:Paralysis, Hyperkalemic Periodic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D013785:Thailand
chemical_list: C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying