Changes in the frequency of theta oscillation during REM sleep after SD are associated with Cyp4a32.

(A) Spectral profiles of the REM sleep EEG for 2 strains displaying an opposite shift in the frequency of theta oscillations after SD relative to baseline. This shift was quantified by the decrease and increase in TPF for BXD61 and BXD101, respectively (see panel F). (B) Hiveplot for the SD-induced shift in TPF. (C) One significant QTL for the TPF shift was detected on chromosome 4 and 1 suggestive QTL on chromosome 8. Prioritization yielded Cyp4a32 as the top-ranked significant gene, based on the significant cis-eQTL modifying its expression in liver and a predicted damaging variation (V314E). (D) Effects of SD and genotype on liver Cyp4a32 expression. Carrying a B6-allele at the Cyp4a32 cis-eQTL–associated marker greatly decreased its expression. (E) Hiveplot for the SD-induced shift in TPF, highlighting Cyp4a32’s links to the amino acid Valine and the chromosome 4 eQTL marker. (F) Strain distribution patterns for TPF differences and liver Cyp4a32 expression after SD. B6-allele carriers at the chromosome 4–associated region had lower Cyp4a32 liver expression and a decrease in TPF after SD, while D2-carriers increase TPF and have higher Cyp4a32 expression. CPM, counts per million; Ctr, control; Cyp4a32, Cytochrome P450, family 4, subfamily a, polypeptide 32; DE, differential expression; EEG, electroencephalography; eQTL, expression quantitative trait locus; lod, logarithm of odds ratio; QTL, quantitative trait locus; SD, sleep deprivation; TPF, theta-peak frequency