TY - JOUR
T1 - Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways
AU - The 23andMe Research Team
AU - Jansen, Philip R.
AU - Watanabe, Kyoko
AU - Stringer, Sven
AU - Skene, Nathan
AU - Bryois, Julien
AU - Hammerschlag, Anke R.
AU - de Leeuw, Christiaan A.
AU - Benjamins, Jeroen S.
AU - Muñoz-Manchado, Ana B.
AU - Nagel, Mats
AU - Savage, Jeanne E.
AU - Tiemeier, Henning
AU - White, Tonya
AU - Agee, Michelle
AU - Alipanahi, Babak
AU - Auton, Adam
AU - Bell, Robert K.
AU - Bryc, Katarzyna
AU - Elson, Sarah L.
AU - Fontanillas, Pierre
AU - Furlotte, Nicholas A.
AU - Hinds, David A.
AU - Huber, Karen E.
AU - Kleinman, Aaron
AU - Litterman, Nadia K.
AU - McCreight, Jennifer C.
AU - McIntyre, Matthew H.
AU - Mountain, Joanna L.
AU - Noblin, Elizabeth S.
AU - Northover, Carrie A. M.
AU - Pitts, Steven J.
AU - Sathirapongsasuti, J. Fah
AU - Sazonova, Olga V.
AU - Shelton, Janie F.
AU - Shringarpure, Suyash
AU - Tian, Chao
AU - Wilson, Catherine H.
AU - Tung, Joyce Y.
AU - Hinds, David A.
AU - Vacic, Vladimir
AU - Wang, Xin
AU - Sullivan, Patrick F.
AU - van der Sluis, Sophie
AU - Polderman, Tinca J. C.
AU - Smit, August B.
AU - Hjerling-Leffler, Jens
AU - van Someren, Eus J. W.
AU - Posthuma, Danielle
AU - Agee, Michelle
AU - Alipanahi, Babak
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85062106137
U2 - 10.1038/s41588-018-0333-3
DO - 10.1038/s41588-018-0333-3
M3 - Article
C2 - 30804565
SN - 1061-4036
VL - 51
SP - 394
EP - 403
JO - Nature genetics
JF - Nature genetics
IS - 3
ER -
SDG 3 Good Health and Well-being