Genetic and Immunologic Aspects of Sleep and Sleep Disorders James M. Parish, MD, FCCP  CHEST  Volume 143, Issue 5, Pages 1489-1499 (May 2013) DOI: 10.1378/chest.12-1219 Copyright © 2013 The American College of Chest Physicians Terms and Conditions

Figure 1 Power spectral analysis demonstrating the genetic influence on sleep EEG frequency power density. A, A female MZ twin pair with virtually identical EEG frequency power density. B, A single individual recorded on two different occasions. C, EEG frequency of a male MZ twin pair with virtually identical EEG power density. D, A male DZ twin pair with different EEG power spectrums. DZ = dizygous; MZ = monozygous. (Adapted with permission from Andretic et al.5) CHEST 2013 143, 1489-1499DOI: (10.1378/chest.12-1219) Copyright © 2013 The American College of Chest Physicians Terms and Conditions

Figure 2 Diagram of the molecular basis of the circadian sleep-wake cycle. The BMAL1 and CLOCK genes are transcribed to proteins BMAL1 and CLOCK, which combine to create a transcription factor BMAL1/CLOCK, which facilitates transcription of the PER and CRY proteins from their respective genes. PER and CRY form a dimer in the cytoplasm that gradually increases in concentration in the cytoplasm and reenters the nucleus, providing negative feedback. CK1ε CSNK1E facilitates degradation of PER. ROR1 and REV-ERBα regulate BMAL1. (Adapted with permission from Lowrey et al.83) CHEST 2013 143, 1489-1499DOI: (10.1378/chest.12-1219) Copyright © 2013 The American College of Chest Physicians Terms and Conditions

Figure 3 Genome-wide association study (GWAS) of restless legs syndrome (RLS). A Manhattan plot diagram of a GWAS demonstrating a common method of displaying data from a GWAS. The x axis shows various chromosome locations. The y axis displays the negative logarithm of the association P value. Each dot in the display represents different single nucleotide polymorphisms (SNPs), possibly linked to RLS. The stronger the association, the smaller the P value and the higher the negative logarithm. The higher the dot on the display, the more likely it is that the SNP is statistically different among those with the disease and those without it. In this display, 13 SNPs are significant and highlighted in bold (three SNPs on chromosome 15 are similar and appear as a single dot.) Gb = gigabases. (Adapted with permission from Winkelmann et al.24) CHEST 2013 143, 1489-1499DOI: (10.1378/chest.12-1219) Copyright © 2013 The American College of Chest Physicians Terms and Conditions