Molecular genetic overlap between posttraumatic stress disorder and sleep phenotypes
Authors: Lind Mackenzie J , Brick Leslie A , Gehrman Philip R , Duncan Laramie E , Gelaye Bizu , Maihofer Adam X , Nievergelt Caroline M , Nugent Nicole R , Stein Murray B , Amstadter Ananda B ,   Psychiatric Genomics Consortium Posttraumatic Stress Disorder, Aiello Allison E , Almli Lynn M , Amstadter Ananda B , Andersen Søren B , Andreassen Ole A , Arbisi Paul A , Ashley-Koch Allison E , Atkinson Elizabeth G , Austin S Bryn , Avdibegovic Esmina , Babić Dragan , Bækvad-Hansen Marie , Baker Dewleen G , Beckham Jean C , Bierut Laura J , Bisson Jonathan I , Boks Marco P , Bolger Elizabeth A , Børglum Anders D , Bradley Bekh , Brashear Megan , Breen Gerome , Bryant Richard A , Bustamante Angela C , Bybjerg-Grauholm Jonas , Calabrese Joseph R , Caldas-de-Almeida José M , Chen Chia-Yen , Coleman Jonathan R I , Dale Anders M , Dalvie Shareefa , Daly Mark J , Daskalakis Nikolaos P , Deckert Jürgen , Delahanty Douglas L , Dennis Michelle F , Disner Seth G , Domschke Katharina , Duncan Laramie E , Dzubur-Kulenovic Alma , Erbes Christopher R , Evans Alexandra , Farrer Lindsay A , Feeny Norah C , Flory Janine D , Forbes David , Franz Carol E , Galea Sandro , Garrett Melanie E , Gelaye Bizu , Gelernter Joel , Geuze Elbert , Gillespie Charles , Uka Aferdita Goci , Gordon Scott D , Guffanti Guia , Haas Magali , Hammamieh Rasha , Hauser Michael A , Heath Andrew C , Hemmings Sian M J , Hougaard David Michael , Jakovljevic Miro , Jett Marti , Johnson Eric Otto , Jones Ian , Jovanovic Tanja , Junglen Angela G , Karstoft Karen-Inge , Kaufman Milissa L , Kessler Ronald C , Khan Alaptagin , Kimbrel Nathan A , King Anthony P , Koen Nastassja , Koenen Karestan C , Kranzler Henry R , Kremen William S , Lawford Bruce R , Lebois Lauren A M , Lewis Catrin E , Liberzon Israel , Linnstaedt Sarah D , Logue Mark W , Lori Adriana , Lugonja Bozo , Luykx Jurjen J , Lyons Michael J , Maihofer Adam X , Maples-Keller Jessica , Marmar Charles , Martin Nicholas G , Maurer Douglas , Mavissakalian Matig R , McFarlane Alexander , McGlinchey Regina E , McLaughlin Katie A , McLean Samuel A , McLeay Sarah , Mehta Divya , Milberg William P , Miller Mark W , Morey Rajendra A , Morris Charles Phillip , Mors Ole , Mortensen Preben B , Nelson Elliot C , Nievergelt Caroline M , Nordentoft Merete , Norman Sonya B , O’Donnell Meaghan , Orcutt Holly K , Panizzon Matthew S , Peters Edward S , Peterson Alan L , Peverill Matthew , Pietrzak Robert H , Polusny Melissa A , Qin Xue-Jun , Ratanatharathorn Andrew , Ressler Kerry J , Rice John P , Risbrough Victoria B , Roberts Andrea L , Rothbaum Alex O , Rothbaum Barbara O , Roy-Byrne Peter , Ruggiero Ken , Rung Ariane , Rutten Bart P F , Saccone Nancy L , Sanchez Sixto E , Schijven Dick , Seedat Soraya , Seligowski Antonia V , Seng Julia S , Sheerin Christina M , Silove Derrick , Smith Alicia K , Smoller Jordan W , Sponheim Scott R , Stein Dan J , Stein Murray B , Stevens Jennifer S , Teicher Martin H , Thompson Wesley K , Torres Katy , Trapido Edward , Uddin Monica , Ursano Robert J , van den Heuvel Leigh Luella , van Hooff Miranda , Vermetten Eric , Vinkers Christiaan H , Voisey Joanne , Wang Yunpeng , Wang Zhewu , Werge Thomas , Williams Michelle A , Williamson Douglas E , Winternitz Sherry , Wolf Christiane , Wolf Erika J , Wolff Jonathan D , Yehuda Rachel , Young Keith A , McD Young Ross , Zhao Hongyu , Zoellner Lori A 
Published: December 2019

Study Objectives

Sleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep and PTSD. Here, we estimate genetic correlations between multiple sleep phenotypes (including insomnia symptoms, sleep duration, daytime sleepiness, and chronotype) and PTSD, using results from the largest genome-wide association study (GWAS) to date of PTSD, as well as publicly available GWAS results for sleep phenotypes within UK Biobank data (23 variations, encompassing four main phenotypes).

Methods

Genetic correlations were estimated utilizing linkage disequilibrium score regression (LDSC), an approach that uses GWAS summary statistics to compute genetic correlations across traits, and Mendelian randomization (MR) analyses were conducted to follow up on significant correlations.

Results

Significant, moderate genetic correlations were found between insomnia symptoms (rg range 0.36–0.49), oversleeping (rg range 0.32–0.44), undersleeping (rg range 0.48–0.49), and PTSD. In contrast, there were mixed results for continuous sleep duration and daytime sleepiness phenotypes, and chronotype was not correlated with PTSD. MR analyses did not provide evidence for casual effects of sleep phenotypes on PTSD.

Conclusion

Sleep phenotypes, particularly insomnia symptoms and extremes of sleep duration, have shared genetic etiology with PTSD, but causal relationships were not identified. This highlights the importance of further investigation into the overlapping influences on these phenotypes as sample sizes increase and new methods to investigate directionality and causality become available.