Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesPersistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10-8) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.Netherlands Organization for Scientific Research NWO Brain & Cognition 433-09-228 European Research Council ERC-ADG-2014-671084 INSOMNIA Netherlands Scientific Organization (NWO) VU University (Amsterdam, the Netherlands) Dutch Brain Foundation Helmholtz Zentrum Munchen - German Federal Ministry of Education and Research state of Bavaria German Migraine & Headache Society (DMKG) Almirall AstraZeneca Berlin Chemie Boehringer Boots Health Care GlaxoSmithKline Janssen Cilag McNeil Pharma MSD Sharp Dohme Pfizer Institute of Epidemiology and Social Medicine at the University of Munster German Ministry of Education and Research (BMBF) German Restless Legs Patient Organisation (RLS Deutsche Restless Legs Vereinigung) Swiss RLS Patient Association (Schweizerische Restless Legs Selbsthilfegruppe

Neurobiology of Sleep-Related Movements

Sleep-related movements comprise a broad spectrum of simple and usually stereotyped movements that are sometimes associated with sleep disturbance (insomnia, sleep fragmentation, and non-restorative sleep). They may represent a physiological variant or a sleep disorder, depending on their intensity, frequency, and associated sleep disruption degree. Sleep-related movements involve usually the lower limbs; they can be idiopathic or associated with other sleep disorders, neurological disease, and medical condition or occur as a consequence of drug use. Several pathophysiological hypotheses have been proposed, but for the majority of these disorders, the neurobiological mechanism is far from being completely understood. Further studies are needed to elucidate the pathophysiology of sleep-related movements in order to better appreciate their clinical significance. This chapter describes the neurobiology of sleep-related movements, namely, periodic limb movements, alternating leg muscle activation, hypnagogic foot tremor, high-frequency myoclonus, excessive fragmentary myoclonus, propriospinal myoclonus at sleep onset, neck myoclonus during sleep, sleep bruxism, sleep-related rhythmic movement disorder, sleep-related leg cramps, and sleep starts. We also present a mechanistic model of the potential role of the spinal central pattern generator for locomotion in generating the leg movements