Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8.4% (s.e.=0.6%). GWAS identified one genome-wide significant hit (Affymetrix id 1:64178756_C_T; P=1.36 × 10^-11). Linkage disequilibrium score regression and polygenic profile score analyses were used to test for shared genetic aetiology between tiredness and up to 29 physical and mental health traits from GWAS consortia. Significant genetic correlations were identified between tiredness and body mass index (BMI), C-reactive protein, high-density lipoprotein (HDL) cholesterol, forced expiratory volume, grip strength, HbA1c, longevity, obesity, self-rated health, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder, neuroticism, schizophrenia and verbal-numerical reasoning (absolute r_g effect sizes between 0.02 and 0.78). Significant associations were identified between tiredness phenotypic scores and polygenic profile scores for BMI, HDL cholesterol, low-density lipoprotein cholesterol, coronary artery disease, C-reactive protein, HbA1c, height, obesity, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, childhood cognitive ability, neuroticism, bipolar disorder, major depressive disorder and schizophrenia (standardised β's had absolute values<0.03). These results suggest that tiredness is a partly heritable, heterogeneous and complex phenomenon that is phenotypically and genetically associated with affective, cognitive, personality and physiological processes.

中文翻译：

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遗传因素对自我报告的疲劳的影响。


自我报告的疲劳和精力不足（通常称为疲劳）与较差的身心健康有关。双胞胎研究表明，其遗传力在 6% 到 50% 之间。在英国生物银行样本 (N=108 976) 中，我们针对以下问题开展了全基因组关联研究 (GWAS)：“在过去两周内，您多久感到疲倦或精力不足？”单变量 GCTA-GREML 发现，对于这个疲劳问题，由所有常见单核苷酸多态性解释的方差比例为 8.4% (se=0.6%)。 GWAS 确定了一个全基因组显着命中（Affymetrix id 1:64178756_C_T；P=1.36 × 10 ^-11 ）。使用连锁不平衡评分回归和多基因谱评分分析来测试疲劳与来自 GWAS 联盟的多达 29 种身心健康特征之间的共同遗传病因。疲劳与体重指数 (BMI)、C 反应蛋白、高密度脂蛋白 (HDL) 胆固醇、用力呼气量、握力、糖化血红蛋白 (HbA1c)、寿命、肥胖、自评健康、吸烟状况、甘油三酯、2 型糖尿病、腰臀比、注意力缺陷多动障碍、双相情感障碍、重度抑郁症、神经质、精神分裂症和语言-数字推理（绝对 r _g效应大小在 0.02 到 0.78 之间）。 疲劳表型评分与 BMI、HDL 胆固醇、低密度脂蛋白胆固醇、冠状动脉疾病、C 反应蛋白、HbA1c、身高、肥胖、吸烟状况、甘油三酯、2 型糖尿病、腰围等多基因谱评分之间存在显着相关性。臀围比、儿童认知能力、神经质、双相情感障碍、重度抑郁症和精神分裂症（标准化β的绝对值<0.03）。这些结果表明，疲劳是一种部分遗传的、异质性和复杂的现象，在表型和遗传上与情感、认知、个性和生理过程相关。