. CC-BY 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/373555 doi: bioRxiv preprint first posted online Jul. 22, 2018; Main Text 1 Type 1 narcolepsy (T1N) is a sleep disorder that affects 1/3,000 individuals across ethnic 2 groups 1-3 . Onset is typically in childhood through early adulthood. Symptoms are caused by the 3 destruction of hypocretin/orexin neurons, a small neuronal subpopulation of the hypothalamus 4 . 4Although the disease is considered autoimmune, the exact mechanism leading to hypocretin cell 5 death is still unclear. Indeed, T1N is strongly associated with alleles encoding the heterodimer 6 DQ0602 haplotype (HLA-DQA1*01:02~DQB1*06:02, 97% vs. 25%) across ethnic groups 5,6 . 7Other loci previously associated with the disease include T cell receptor (TCR) loci alpha (TRA) 8 and beta (TRB), receptors of HLA-peptide presentations, and other autoimmune associated 9 genes (CTSH, P2RY11, ZNF365, IFNAR1 and TNFSF4) [7][8][9][10] . 11Triggers of T1N point to the immune system, including influenza and Streptococcus Pyogenes 12 infections 9,11,12 , as well as immunization with Pandemrix®, an influenza-A vaccine developed 13 specifically against the H1N1 "swine flu" strain 13-20 suggest a strong environmental modifier of 14 disease risk for narcolepsy. Increased T1N incidence following the Pandemrix® vaccination was 15 first seen in Northern Europe [13][14][15][16][17][18][19][20] with 8-fold increase in incidence in (0.79/100,000 to 16 6.3/100,000) in children. The specificity was striking, as increased T1N was later detected in all 17 countries where Pandemrix® was used, whereas countries using other pH1N1 vaccine brands 18 did not detect vaccination-associated increases in incidence [13][14][15][16][17][18][19][20][21][22] . is defined by antigen presentation, mediated through specific T cell receptor chains, and 27 modulated by influenza-A as a critical trigger. 28. CC-BY 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/373555 doi: bioRxiv preprint first posted online Jul. 22, 2018; examined using LD Score Regression 33 , the shared heritability was largest with type-1 diabetes Genetics of vaccination-triggered narcolepsy. We have previously shown that both influenza 21 infections and, in rare cases, immunization with Pandemrix® can trigger narcolepsy 13,18,19,42,43 . 22The baseline for narcolepsy in unvaccinated vs. Pandemrix® vaccinated individuals was 23 0.7/100,000 vs. 9/100,000 person years with on average 10-fold increase in risk 13,18,19,[42][43][44] was not peer-reviewed) is t...

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Conclusion:In this largest admixture mapping study of AHI in Hispanic/Latino Americans, a novel genomic region was identified to harbor OSA related variants. Future association analysis may identify genetic variants that explain sleep apnea susceptibility and its variation across ancestral groups.

Introduction: Sleep spindles are associated with various aspects of learning and memory and are potential biomarkers of neuropsychiatric disease. Although twin studies indicate that spindle activity is partially heritable, specific genes are yet to be identified. Here we detect and characterize spindle phenotypes in 11,630 individuals (aged 5 to 95), confirm their heritable basis and initiate genome-wide association analyses to map individual genes. Methods: We compiled whole-night polysomnography, demographic and medical data from the US National Sleep Research Resource (NSRR), applying automated artifact rejection and wavelet analyses to detect spindles from two central electrodes. Univariate heritabilities and genetic correlations were estimated using within-family intraclass correlations and variance components models for the genome-wide single nucleotide polymorphism (SNP) data. Results: Spindle and spectral phenotypes demonstrated high test-retest reliabilities (r>0.8), based on over 4,000 individuals with repeated polysomnograms. We identified and corrected potential confounders that might impact genetic studies, including body mass index (mediated by cardiac interference in the EEG) and age. In 730 individuals from the Cleveland Family Study, spindle density was highly heritable in both white (h 2 = 0.45, p = 8x10 -6 ) and black individuals (h 2 = 0.43, p = 3x10 -6 ), adjusting for age and sex. Spindle density in stage 3 sleep (N3) had a high genetic overlap (r G = 0.89, p = 2x10 -4 in whites, r G = 0.88, p = 1x10 -5 in blacks) with N2 spindles. In contrast, fast (15Hz) and slow (11Hz) spindles showed significant heritabilities but no genetic overlap (r G = -0.15 and 0.16, p = 0.31 and 0.18 for whites and blacks respectively), suggesting distinct genetic architectures. These results will help in the optimal selection of independent phenotypes for ongoing genome-wide association analyses, the results of which are expected early 2017. Conclusion: We observed evidence for robust genetic influences on spindle phenotypes, controlling for a range of demographic and clinical covariates. This work can inform future genetic studies that aim to understand better the genetic architecture of spindles and their relation to health and disease.