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Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals.
Xu, Huajun; Liu, Feng; Li, Zhiqiang; Li, Xinyi; Liu, Yuenan; Li, Niannian; Zhang, Xiaoxu; Gao, Zhenfei; Zhang, Xiaoman; Liu, Yupu; Zou, Jianyin; Meng, Lili; Liu, Suru; Zhu, Huaming; Tang, Xulan; Wu, Hongmin; Su, Kaiming; Chen, Bin; Yu, Dongzhen; Ye, Haibo; Chen, Haoyan; Yi, Hongliang; Yin, Shankai; Guan, Jian; Shi, Yongyong.
Afiliación
  • Xu H; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Liu F; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Li Z; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Li X; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Liu Y; The Affiliated Hospital of Qingdao University & the Biomedical Sciences Institute of Qingdao University, Qingdao Branch of SJTU Bio-X Institutes, Qingdao University, Qingdao, China; and.
  • Li N; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), the Collaborative Innovation Center for Brain Science, and.
  • Zhang X; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Gao Z; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Zhang X; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Liu Y; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Zou J; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Meng L; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Liu S; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Zhu H; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Tang X; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Wu H; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Su K; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Chen B; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Yu D; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Ye H; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Chen H; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Yi H; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Yin S; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Guan J; Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai, China.
  • Shi Y; Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Am J Respir Crit Care Med ; 206(12): 1534-1545, 2022 12 15.
Article en En | MEDLINE | ID: mdl-35819321
ABSTRACT
Rationale Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained.

Objectives:

To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles.

Methods:

A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main

Results:

Two characteristic study-wide significant loci (P < 2.63 × 10-9) for OSA were identified the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 × 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 × 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity.

Conclusions:

We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Apnea Obstructiva del Sueño / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Am J Respir Crit Care Med Asunto de la revista: TERAPIA INTENSIVA Año: 2022 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Apnea Obstructiva del Sueño / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Am J Respir Crit Care Med Asunto de la revista: TERAPIA INTENSIVA Año: 2022 Tipo del documento: Article País de afiliación: China