A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis

作者：Jongjaroenprasert Wallaya^*; Phusantisampan Theerawut; Mahasirimongkol Surakameth; Mushiroda Taisei; Hirankarn Nattiya; Snabboon Thiti; Chanprasertyotin Suwannee; Tantiwong Puntip; Soonthornpun Supamai; Rattanapichart Paninee; Mamanasiri Sunee; Himathongkam Thep; Ongphiphadhanakul Boonsong; Takahashi Atsushi; Kamatani Naoyuki; Kubo Michiaki; Nakamura Yusuke

来源：Journal of Human Genetics, 2012, 57(5): 301-304.

DOI：10.1038/jhg.2012.20

• genome-wide association study
• hyperthyroidism
• hypokalemic periodic paralysis

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=2.09x10(-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%26apos;s adjustment (P=3.23x10(-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=3.44x10(-5), OR=5.13; 95% CI=1.87-14.1; combined-analysis P=3.71x10(-12), OR=5.47; 95% CI=3.04-9.83). Journal of Human Genetics (2012) 57, 301-304; doi:10.1038/jhg.2012.20; published online 8 March 2012

• 出版日期2012-5
• 单位河北医科大学