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Evaluating the role of rare genetic variation in sleep duration

  • Author Footnotes
    # The three authors contributed equally to this work.
    Peilin Meng
    Footnotes
    # The three authors contributed equally to this work.
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Author Footnotes
    # The three authors contributed equally to this work.
    Chuyu Pan
    Footnotes
    # The three authors contributed equally to this work.
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Author Footnotes
    # The three authors contributed equally to this work.
    Shiqiang Cheng
    Footnotes
    # The three authors contributed equally to this work.
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Chun'e Li
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Yao Yao
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Li Liu
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Bolun Cheng
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Xuena Yang
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Zhen Zhang
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Yujing Chen
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Jingxi Zhang
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Huijie Zhang
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Yan Wen
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Yumeng Jia
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Xiong Guo
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
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  • Feng Zhang
    Correspondence
    Corresponding author: Feng Zhang, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China 710061.
    Affiliations
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
    Search for articles by this author
  • Author Footnotes
    # The three authors contributed equally to this work.

      Abstract

      Objectives

      To explore the roles of rare and high-impact variants in sleep duration.

      Design

      Based on the recently released UK Biobank 200k exome dataset, an exome-wide association study was conducted to detect rare variants (minor allele frequency <0.01) contributing to sleep duration. Variant annotations were performed by the software tool ANNOVAR. Gene-based burden tests of sleep duration were conducted by the SKAT R-package. After quality control, 137,047 subjects were included in this study. CAUSALdb database was used to explore the related mental traits of identified genes.

      Results

      We detected 730,572 variants with MAF < 1%, including 3873 frameshift variants, 3977 nonframeshift variants, 449,632 nonsynonymous variants, 1293 startloss variants, 10,254 stopgain variants, 413 stoploss variants, 261,130 synonymous variants, and 3102 variants are annotated as unknown. The burden test of exonic variants detected two exome-wide significant associations for sleep duration including TMIE at 3p21.31 (PBonferroni adjusted = 0.015) and ZIC2 at 13q32.3 (PBonferroni adjusted = 0.047). There are only nonsynonymous contained in TMIE; as for ZIC2, we detected 2 annotations of variants: nonsynonymous (PBonferroni adjusted =2.04 × 10−4) and nonframeshift (PBonferroni adjusted =0.85). TMIE and ZIC2 were reported to be associated with several mental traits, such as chronotype, depression, and brain natriuretic peptide in published study.

      Conclusion

      This study reported 2 novel candidate genes for a sleep duration, supporting the roles of rare genetic variants in the regulation of sleep duration.

      Keywords

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