TY - JOUR
T1 - A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis
AU - Jongjaroenprasert, Wallaya
AU - Phusantisampan, Theerawut
AU - Mahasirimongkol, Surakameth
AU - Mushiroda, Taisei
AU - Hirankarn, Nattiya
AU - Snabboon, Thiti
AU - Chanprasertyotin, Suwannee
AU - Tantiwong, Puntip
AU - Soonthornpun, Supamai
AU - Rattanapichart, Paninee
AU - Mamanasiri, Sunee
AU - Himathongkam, Thep
AU - Ongphiphadhanakul, Boonsong
AU - Takahashi, Atsushi
AU - Kamatani, Naoyuki
AU - Kubo, Michiaki
AU - Nakamura, Yusuke
PY - 2012/5
Y1 - 2012/5
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=84861632259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861632259&partnerID=8YFLogxK
U2 - 10.1038/jhg.2012.20
DO - 10.1038/jhg.2012.20
M3 - Article
C2 - 22399142
AN - SCOPUS:84861632259
SN - 1434-5161
VL - 57
SP - 301
EP - 304
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 5
ER -