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  • Association of DAT1 genetic variants with habitual sleep duration in the UK Biobank SLEEP Rhodes, J. A., Lane, J. M., Vlasac, I. M., Rutter, M. K., Czeisler, C. A., Saxena, R. 2019; 42 (1)

    Abstract

    Short sleep duration has been linked to negative health effects, but is a complex phenotype with many contributing factors, including genetic. We evaluated 27 common single nucleotide polymorphisms (SNPs) in candidate genes previously reported to be associated with other sleep variables for association with self-reported habitual sleep duration in the UK Biobank in 111 975 individuals of European ancestry. Genetic variation in DAT1 (rs464049) was significantly associated with sleep duration after correction for multiple testing (p = 4.00 × 10-5), whereas SNPs correlated to a previously studied variable number tandem repeat (VNTR) in DAT1 were not significant in this population. We also replicated a previously reported association in DRD2. Independent replication of these associations and a second signal in DRD2 (rs11214607) was observed in an additional 261 870 participants of European ancestry from the UK Biobank. Meta-analysis confirmed genome-wide significant association of DAT1 rs464049 (G, beta [standard error, SE] = -0.96 [0.18] minutes/allele, p = 5.71 × 10-10) and study-wide significant association of DRD2 (rs17601612, C, beta [SE] = -0.66 [0.18] minutes/allele, p = 1.77 × 10-5; rs11214607, C, beta [SE] = 1.08 (0.24) minutes/allele, p = 1.39 × 10-6). Overall, SNPs in two dopamine-related genes were significantly associated with sleep duration, highlighting the important link of the dopamine system with adult sleep duration in humans.

    View details for DOI 10.1093/sleep/zsy193

    View details for Web of Science ID 000459345300005

    View details for PubMedID 30299516

    View details for PubMedCentralID PMC6335867

  • Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates NATURE COMMUNICATIONS Dashti, H. S., Jones, S. E., Wood, A. R., Lane, J. M., van Hees, V. T., Wang, H., Rhodes, J. A., Song, Y., Patel, K., Anderson, S. G., Beaumont, R. N., Bechtold, D. A., Bowden, J., Cade, B. E., Garaulet, M., Kyle, S. D., Little, M. A., Loudon, A. S., Luik, A., Scheer, F. L., Spiegelhalder, K., Tyrrell, J., Gottlieb, D. J., Tiemeier, H., Ray, D. W., Purcell, S. M., Frayling, T. M., Redline, S., Lawlor, D. A., Rutter, M. K., Weedon, M. N., Saxena, R. 2019; 10: 1100

    Abstract

    Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10-8; 43 loci at p < 6 × 10-9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10-4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.

    View details for DOI 10.1038/s41467-019-08917-4

    View details for Web of Science ID 000460509900002

    View details for PubMedID 30846698

    View details for PubMedCentralID PMC6405943