EEG delta power in NREM sleep after SD is associated with <i>Kif16b</i> and <i>Wrn</i>.
Shanaz Diessler
Maxime Jan
Yann Emmenegger
Nicolas Guex
Benita Middleton
Debra J. Skene
Mark Ibberson
Frederic Burdet
Lou Götz
Marco Pagni
Martial Sankar
Robin Liechti
Charlotte N. Hor
Ioannis Xenarios
Paul Franken
10.1371/journal.pbio.2005750.g005
https://plos.figshare.com/articles/figure/EEG_delta_power_in_NREM_sleep_after_SD_is_associated_with_i_Kif16b_i_and_i_Wrn_i_/6952949
<p>(A) NREM sleep EEG spectra in the first 3 h after SD (ZT6–9) for the 2 BXD lines that displayed the lowest and highest EEG activity in the fast delta frequency band (2.5–4.25 Hz, δ2; top, see panel E) and for the 2 BXD lines that displayed the smallest and largest increase (or gain) in EEG power in the slow delta band (1.0–2.25 Hz, δ1; bottom, see panel E). Spectra were “1/f-corrected” (and therefore not directly comparable to the values in panel E) for better visualization of activity in higher frequency bands (theta [5–9 Hz, θ], sigma [11–16 Hz, σ], beta [18–30 Hz, β], and slow [32–55 Hz, γ1] and fast gamma [55–80 Hz, γ2]). Subsequent analyses were performed without this correction. (B) QTL mapping and prioritization for δ2 power identified a significant association on chromosome 2 and <i>Kif16b</i> in cortex as top-ranked gene (top). For the δ1 increase after SD, we obtained a suggestive QTL on chromosome 8 and a significant prioritization score for the DNA-helicase <i>Wrn</i>. (C) Hiveplot visualization of network connections for the δ1 and δ2 power after SD (top-left panels) and the SD-induced increase in δ1 and δ2 power over baseline (bottom-left panels). Note the marked differences in the networks and QTLs regulating the expression of these 2 delta bands. Right hiveplots highlight <i>Kif16b</i> in the δ2 power–associated network (top), and <i>Wrn</i> in the network associated with the δ1 increase (bottom). Only <i>Kif16b</i> expression in the cortex was linked to the chromosome 2 <i>cis</i>-<i>e</i>QTL and was not associated with any metabolite. <i>Wrn</i> expression was significantly linked to the chromosome 8 <i>cis-e</i>QTL and to the long phosphatidylcholine, PC-ae-C38:5. (D) <i>Kif16b</i> is highly significantly down-regulated in cortex (left), while it remains unchanged in liver after SD (<i>p</i> = 0.15; not shown). Also, <i>Wrn</i> expression was strongly down-regulated by SD in cortex (right) and only marginally so, albeit significantly, in liver (<i>p</i> = 0.02; not shown). (E) Strain distribution patterns. BXD lines carrying a <i>B6-</i>allele on the chromosome 2–associated region showed higher δ2 power after SD (left) and a significantly higher <i>Kif16b</i> expression (<i>p</i> = 1.3e−15; second to left) than <i>D2-</i>allele carriers. <i>D2-</i>allele carriers of the chromosome 8–associated region showed a larger δ1 increase after SD (second to right) as well as a significantly larger decrease in <i>Wrn</i> expression after SD (right) than <i>B6-</i>allele carriers. For color-coding of genotypes, see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005750#pbio.2005750.g004" target="_blank">Fig 4</a>. CPM, counts per million; Ctr, control; EEG, electroencephalography; <i>e</i>QTL, expression quantitative trait locus; FDR, false discovery rate; <i>Kif16b</i>, <i>Kinesin family member 16B</i>; NREM, non-REM; PC-ae, phosphatidylcholine acyl-alkyl; QTL, quantitative trait locus; SD, sleep deprivation; <i>Wrn</i>, <i>Werner syndrome RecQ like helicase</i>; ZT, zeitgeber time</p>
2018-08-09 18:03:56
AMPA
acid turnover
analyses
baseline conditions
systems genetics approach
BXD
knowledge base
systems genetics resource
plasma metabolome data
GRP
prioritize candidate genes
-3-hydroxy acid
systems genetics
transcriptome
mouse Sleep
substrate
reference population
systems genetics landscape
receptor trafficking
SD