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Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study.
Zhao, Shuang-Xia; Liu, Wei; Liang, Jun; Gao, Guan-Qi; Zhang, Xiao-Mei; Yao, Yu; Wang, Hai-Ning; Yuan, Fei-Fei; Xue, Li-Qiong; Ma, Yu-Ru; Zhang, Le-Le; Ye, Xiao-Ping; Zhang, Qian-Yue; Sun, Feng; Zhang, Rui-Jia; Yang, Shao-Ying; Zhan, Ming; Du, Wen-Hua; Liu, Bing-Li; Chen, Xia; Song, Zhi-Yi; Li, Xue-Song; Li, Ping; Ru, Ying; Zuo, Chun-Lin; Li, Sheng-Xian; Han, Bing; Zhu, Hui; Qiao, Jie; Xuan, Miao; Su, Bin; Sun, Fei; Ma, Jun-Hua; Chen, Jia-Lun; Tian, Hao-Ming; Chen, Sai-Juan; Song, Huai-Dong.
Afiliação
  • Zhao SX; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Liu W; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Liang J; Department of Endocrinology, The Central Hospital of Xuzhou Affiliated to Xuzhou Medical College, Xuzhou, Jiangsu, China.
  • Gao GQ; Department of Endocrinology, People's Hospital of Linyi, Linyi, Shandong, China.
  • Zhang XM; Department of Endocrinology, The First Hospital Affiliated to Bengbu Medical College, Bengbu, Anhui, China.
  • Yao Y; Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Wang HN; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Yuan FF; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Xue LQ; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Ma YR; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Zhang LL; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Ye XP; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Zhang QY; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Sun F; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Zhang RJ; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Yang SY; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Zhan M; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Du WH; Department of Endocrinology, People's Hospital of Linyi, Linyi, Shandong, China.
  • Liu BL; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Chen X; Department of Endocrinology, Shanghai Fourth People's Hospital, Tongji University, Shanghai, China.
  • Song ZY; Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • Li XS; Department of Endocrinology and Metabolism, Minhang Hospital, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Li P; Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu, China.
  • Ru Y; Department of Endocrinology, Anhui Provincial Hospital, Hefei, Anhui, China.
  • Zuo CL; Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  • Li SX; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Han B; Department of Endocrinology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Zhu H; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Qiao J; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Xuan M; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Su B; Department of Endocrinology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
  • Sun F; Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • Ma JH; Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital, Shanghai, China.
  • Chen JL; Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital, Shanghai, China.
  • Tian HM; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Chen SJ; Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Song HD; The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China.
JAMA Netw Open ; 2(5): e193348, 2019 05 03.
Article em En | MEDLINE | ID: mdl-31050781
ABSTRACT
Importance Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed.

Objective:

To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and

Participants:

This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and

Measures:

Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci.

Results:

A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified DCHS2 on 4q31.3 (rs1352714 odds ratio [OR], 1.58; 95% CI, 1.35-1.85; P = 1.24 × 10-8) and C11orf67 on 11q14.1 (rs2186564 OR, 1.50; 95% CI, 1.29-1.74; P = 2.80 × 10-7). One previously reported specific locus was confirmed on 17q24.3 near KCNJ2 (rs312729 OR, 2.08; 95% CI, 1.83-2.38; P = 8.02 × 10-29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16; P = 7.05 × 10-6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Crise Tireóidea / Doença de Graves Tipo de estudo: Clinical_trials / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País/Região como assunto: Asia Idioma: En Revista: JAMA Netw Open Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Crise Tireóidea / Doença de Graves Tipo de estudo: Clinical_trials / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País/Região como assunto: Asia Idioma: En Revista: JAMA Netw Open Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China