生物
孟德尔随机化
数量性状位点
全基因组关联研究
遗传学
遗传建筑学
遗传力
候选基因
基因
神经科学
生物信息学
单核苷酸多态性
遗传变异
基因型
作者
Philip R. Jansen,Kyoko Watanabe,Sven Stringer,Nathan Skene,Julien Bryois,Anke R. Hammerschlag,Christiaan de Leeuw,Jeroen S. Benjamins,Muñoz-Manchado Ab,Mats Nagel,Savage Je,Henning Tiemeier,Tonya White,Tung Jy,Hinds Da,Vacic,X Wang,Sullivan Pf,Sophie van der Sluis,Smit Ab,Jens Hjerling-Leffler,Van Someren Ejw,Daniëlle Posthuma
出处
期刊:Nature Genetics
[Springer Nature]
日期:2019-02-25
卷期号:51 (3): 394-403
被引量:598
标识
DOI:10.1038/s41588-018-0333-3
摘要
Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints. We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets.
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