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.
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.
Sleep Health. 2022 Oct;8(5):536-541. doi: 10.1016/j.sleh.2022.05.007. Epub 2022 Jul 28.
To explore the roles of rare and high-impact variants in sleep duration.
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.
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 (P = 0.015) and ZIC2 at 13q32.3 (P = 0.047). There are only nonsynonymous contained in TMIE; as for ZIC2, we detected 2 annotations of variants: nonsynonymous (P =2.04 × 10) and nonframeshift (P =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.
This study reported 2 novel candidate genes for a sleep duration, supporting the roles of rare genetic variants in the regulation of sleep duration.
探索罕见和高影响变异在睡眠时间中的作用。
基于最近发布的英国生物库 20 万外显子数据集，进行了外显子全关联研究，以检测导致睡眠时间的罕见变异（次要等位基因频率 <0.01）。通过软件工具 ANNOVAR 进行变异注释。使用 SKAT R 包进行睡眠时间的基因负担测试。经过质量控制，本研究纳入了 137047 名受试者。使用 CAUSALdb 数据库探索已识别基因的相关精神特征。
我们检测到 MAF<1%的 730572 个变体，包括 3873 个移码变异、3977 个非移码变异、449632 个非同义变异、1293 个起始丢失变异、10254 个终止增益变异、413 个终止丢失变异、261130 个同义变异和 3102 个未知变异。外显子变异的负担测试检测到与睡眠时间相关的两个外显子全关联，包括 3p21.31 上的 TMIE（P=0.015）和 13q32.3 上的 ZIC2（P=0.047）。TMIE 中仅包含非同义变异；对于 ZIC2，我们检测到 2 个变异注释：非同义（P=2.04×10）和非移码（P=0.85）。TMIE 和 ZIC2 被报道与几个精神特征相关，如时型、抑郁和脑利钠肽在已发表的研究中。
本研究报告了 2 个与睡眠时间相关的新候选基因，支持罕见遗传变异在调节睡眠时间中的作用。
