Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

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; P(meta-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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CPAP induced reverse atrial electrical remodelling in patients with severe OSA as represented by a significant reduction in SAPW duration.