RESUMEN
Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 × 10(-8)) in the ABCC9 gene that explains ≈5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Canal de Potasio Kv1.3/genética , Polimorfismo de Nucleótido Simple/genética , Trastornos del Sueño-Vigilia/genética , Transportadoras de Casetes de Unión a ATP/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Animales Modificados Genéticamente , Estudios de Cohortes , Drosophila/genética , Drosophila/fisiología , Proteínas de Drosophila/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Miocardio/patología , Fenotipo , Fotoperiodo , Placofilinas/genética , Canales de Potasio de Rectificación Interna/genética , Interferencia de ARN/fisiología , Receptores de Droga/genética , Proteínas Represoras/genética , Receptores de Sulfonilureas , Población Blanca , Adulto JovenRESUMEN
A woman at the presumed age of 60 years was suspected of malingering cognitive impairment, due to her social circumstances (illegal residency) and was consequently unable to give permission for treatment. She was suffering from locally advanced mammary carcinoma, diagnosed according to the Breast Imaging Reporting and Data System in stage 5. In order to assess mental incompetence, an algorithm from the Royal Dutch Medical Association (KNMG) is a useful tool. The algorithm contains questions for determining whether a patient is able to make choices, if he/she understands medical information and can apply this to his/her own situation and whether he/she is able to logically consider the choice. Mental incompetence is a legally defined status - there is no straightforward relation between mental incompetence and the underlying diagnosis, in this case malingering. Since feigning mental incompetence has its own limitations, the subjective judgment of the physician is important. In the case presented, medical treatment i.e. chemotherapy was started in accordance with the Dutch Medical Treatment Contracts Act (WGBO) for a patient with cognitive impairment. Compulsory treatment was not necessary because the patient did not resist either physically or verbally. If a critical situation is to be prevented or is threatening, then there is no difference between genuine or feigned mental incompetence.
