Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness
Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness
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DOI：
10.1093/hmg/ddz219
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发表时间：
2019-11-15
影响因子：
3.5
通讯作者：
Boomsma, Dorret, I
中科院分区：
文献类型：
--
作者：
Abdellaoui, Abdel;Sanchez-Roige, Sandra;Boomsma, Dorret, I
人类是社会性动物，当他们感到缺乏社会联系时会经历强烈的痛苦。现代社会正在经历孤独的流行。虽然孤独的经历是普遍的人类，但有些人报告说比其他人更孤独。孤独症与死亡率的关系比肥胖症更密切，这强调了理解孤独与健康之间关系的本质的必要性。虽然直觉上，诸如婚姻状况和年龄等环境因素会影响孤独感，但也有令人信服的证据表明孤独感的遗传倾向。为了更好地了解孤独的遗传结构及其与相关结果的关系，我们将孤独的全基因组关联研究荟萃分析扩展到511280名受试者，并从16个位点检测到19个显著的遗传变异，包括4个新位点，以及58个显著相关的基因。我们通过计算遗传相关性和在18498个具有EHR数据的独立样本中建立孤独多基因分数来研究与广泛的身心健康特征的遗传重叠，以进行PheWAS。孤独的遗传倾向与心血管疾病、精神疾病、代谢紊乱、甘油三酯和高密度脂蛋白有关。孟德尔随机化分析显示，BMI和体脂对孤独感的影响是因果关系的，而且是递增的。我们的研究结果为未来研究孤独的遗传基础及其与身心健康的关系提供了框架。
Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.