PT  - JOURNAL ARTICLE
AU  - Jacqueline M Lane
AU  - Samuel Jones
AU  - Hassan S Dashti
AU  - Andrew R Wood
AU  - Krishna Aragam
AU  - Vincent T. van Hees
AU  - Ben Brumpton
AU  - Bendik Winsvold
AU  - Heming Wang
AU  - Jack Bowden
AU  - Yanwei Song
AU  - Krunal Patel
AU  - Simon G Anderson
AU  - Robin Beaumont
AU  - David A Bechtold
AU  - Brian Cade
AU  - Sek Kathiresan
AU  - Max A Little
AU  - Annemarie I Luik
AU  - Andrew S Loudon
AU  - Shaun Purcell
AU  - Rebecca C Richmond
AU  - Frank AJL Scheer
AU  - Jessica Tyrrell
AU  - John Winkelman
AU  - HUNT All In Sleep
AU  - Linn B Strand
AU  - Jonas B. Nielsen
AU  - Cristen J. Willer
AU  - Susan Redline
AU  - Kai Spiegelhalder
AU  - Simon D Kyle
AU  - David W Ray
AU  - John-Anker Zwart
AU  - Kristian Hveem
AU  - Timothy M Frayling
AU  - Deborah Lawlor
AU  - Martin K Rutter
AU  - Michael N Weedon
AU  - Richa Saxena
TI  - Biological and clinical insights from genetics of insomnia symptoms
AID  - 10.1101/257956
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 257956
4099  - http://biorxiv.org/content/early/2018/02/02/257956.short
4100  - http://biorxiv.org/content/early/2018/02/02/257956.full
AB  - Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes, but underlying pathophysiological processes and causal relationships with disease are poorly understood. Here we identify 57 loci for self-reported insomnia symptoms in the UK Biobank (n=453,379) and confirm their impact on self-reported insomnia symptoms in the HUNT study (n=14,923 cases, 47,610 controls), physician diagnosed insomnia in Partners Biobank (n=2,217 cases, 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n=83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis, phototransduction and muscle development pathways and of genes expressed in multiple brain regions, skeletal muscle and adrenal gland. Evidence of shared genetic factors is found between frequent insomnia symptoms and restless legs syndrome, aging, cardio-metabolic, behavioral, psychiatric and reproductive traits. Evidence is found for a possible causal link between insomnia symptoms and coronary heart disease, depressive symptoms and subjective well-being.One Sentence Summary We identify 57 genomic regions associated with insomnia pointing to the involvement of phototransduction and ubiquitination and potential causal links to CAD and depression.