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| PMID |
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| TITLE |
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| Molecular genetic overlap between posttraumatic stress disorder and sleep phenotypes. |
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| ABSTRACT |
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| STUDY OBJECTIVES |
NlmCategory: OBJECTIVE |
| 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 |
NlmCategory: METHODS |
| 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). 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 |
NlmCategory: RESULTS |
| 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). 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. 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 |
NlmCategory: CONCLUSIONS |
| 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). 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. 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. 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. |
| © Sleep Research Society 2019. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2019/02/07 |
| revised |
2019/08/17 |
| entrez |
2019/12/06 06:00 |
| pubmed |
2019/12/06 06:00 |
| medline |
2019/12/06 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Lind MJ |
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Lind |
Mackenzie J |
MJ |
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Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, VA. |
| Brick LA |
|
Brick |
Leslie A |
LA |
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Department of Psychiatry and Human Behavior in Alpert Medical School of Brown University, RI. |
| Gehrman PR |
|
Gehrman |
Philip R |
PR |
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Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, PA. |
| Duncan LE |
|
Duncan |
Laramie E |
LE |
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Department of Psychiatry and Behavioral Sciences, Stanford University, CA. |
| Gelaye B |
|
Gelaye |
Bizu |
B |
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Departments of Epidemiology and Psychiatry, Harvard T. H. Chan School of Public Health and Harvard School of Medicine, MA. |
| Maihofer AX |
|
Maihofer |
Adam X |
AX |
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Department of Psychiatry, University of California San Diego and Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, CA. |
| Nievergelt CM |
|
Nievergelt |
Caroline M |
CM |
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Department of Psychiatry, University of California San Diego and Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, CA. |
| Nugent NR |
|
Nugent |
Nicole R |
NR |
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Bradley/Hasbro Children's Research Center of Rhode Island Hospital, RI. |
| Stein MB |
|
Stein |
Murray B |
MB |
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Departments of Psychiatry and Family Medicine & Public Health, University of California San Diego, CA and VA San Diego Healthcare System, CA. |
| Amstadter AB |
|
Amstadter |
Ananda B |
AB |
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Department of Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, VA. |
|
Psychiatric Genomics Consortium Posttraumatic Stress Disorder |
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| INVESTIGATORS |
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| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Aiello |
Allison E |
AE |
|
| Almli |
Lynn M |
LM |
|
| Amstadter |
Ananda B |
AB |
|
| Andersen |
Søren B |
SB |
|
| Andreassen |
Ole A |
OA |
|
| Arbisi |
Paul A |
PA |
|
| Ashley-Koch |
Allison E |
AE |
|
| Atkinson |
Elizabeth G |
EG |
|
| Austin |
S Bryn |
SB |
|
| Avdibegovic |
Esmina |
E |
|
| Babić |
Dragan |
D |
|
| Bækvad-Hansen |
Marie |
M |
|
| Baker |
Dewleen G |
DG |
|
| Beckham |
Jean C |
JC |
|
| Bierut |
Laura J |
LJ |
|
| Bisson |
Jonathan I |
JI |
|
| Boks |
Marco P |
MP |
|
| Bolger |
Elizabeth A |
EA |
|
| Børglum |
Anders D |
AD |
|
| Bradley |
Bekh |
B |
|
| Brashear |
Megan |
M |
|
| Breen |
Gerome |
G |
|
| Bryant |
Richard A |
RA |
|
| Bustamante |
Angela C |
AC |
|
| Bybjerg-Grauholm |
Jonas |
J |
|
| Calabrese |
Joseph R |
JR |
|
| Caldas-de-Almeida |
José M |
JM |
|
| Chen |
Chia-Yen |
CY |
|
| Coleman |
Jonathan R I |
JRI |
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| Dale |
Anders M |
AM |
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| Dalvie |
Shareefa |
S |
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| Daly |
Mark J |
MJ |
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| Daskalakis |
Nikolaos P |
NP |
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| Deckert |
Jürgen |
J |
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| Delahanty |
Douglas L |
DL |
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| Dennis |
Michelle F |
MF |
|
| Disner |
Seth G |
SG |
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| Domschke |
Katharina |
K |
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| Duncan |
Laramie E |
LE |
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| Dzubur-Kulenovic |
Alma |
A |
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| Erbes |
Christopher R |
CR |
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| Evans |
Alexandra |
A |
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| Farrer |
Lindsay A |
LA |
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| Feeny |
Norah C |
NC |
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| Flory |
Janine D |
JD |
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| Forbes |
David |
D |
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| Franz |
Carol E |
CE |
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| Galea |
Sandro |
S |
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| Garrett |
Melanie E |
ME |
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| Gelaye |
Bizu |
B |
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| Gelernter |
Joel |
J |
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| Geuze |
Elbert |
E |
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| Gillespie |
Charles |
C |
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| Uka |
Aferdita Goci |
AG |
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| Gordon |
Scott D |
SD |
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| Guffanti |
Guia |
G |
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| Haas |
Magali |
M |
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| Hammamieh |
Rasha |
R |
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| Hauser |
Michael A |
MA |
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| Heath |
Andrew C |
AC |
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| Hemmings |
Sian M J |
SMJ |
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| Hougaard |
David Michael |
DM |
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| Jakovljevic |
Miro |
M |
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| Jett |
Marti |
M |
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| Johnson |
Eric Otto |
EO |
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| Jones |
Ian |
I |
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| Jovanovic |
Tanja |
T |
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| Junglen |
Angela G |
AG |
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| Karstoft |
Karen-Inge |
KI |
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| Kaufman |
Milissa L |
ML |
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| Kessler |
Ronald C |
RC |
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| Khan |
Alaptagin |
A |
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| Kimbrel |
Nathan A |
NA |
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| King |
Anthony P |
AP |
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| Koen |
Nastassja |
N |
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| Koenen |
Karestan C |
KC |
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| Kranzler |
Henry R |
HR |
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| Kremen |
William S |
WS |
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| Lawford |
Bruce R |
BR |
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| Lebois |
Lauren A M |
LAM |
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| Lewis |
Catrin E |
CE |
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| Liberzon |
Israel |
I |
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| Linnstaedt |
Sarah D |
SD |
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| Logue |
Mark W |
MW |
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| Lori |
Adriana |
A |
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| Lugonja |
Bozo |
B |
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| Luykx |
Jurjen J |
JJ |
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| Lyons |
Michael J |
MJ |
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| Maihofer |
Adam X |
AX |
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| Maples-Keller |
Jessica |
J |
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| Marmar |
Charles |
C |
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| Martin |
Nicholas G |
NG |
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| Maurer |
Douglas |
D |
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| Mavissakalian |
Matig R |
MR |
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| McFarlane |
Alexander |
A |
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| McGlinchey |
Regina E |
RE |
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| McLaughlin |
Katie A |
KA |
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| McLean |
Samuel A |
SA |
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| McLeay |
Sarah |
S |
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| Mehta |
Divya |
D |
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| Milberg |
William P |
WP |
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| Miller |
Mark W |
MW |
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| Morey |
Rajendra A |
RA |
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| Morris |
Charles Phillip |
CP |
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| Mors |
Ole |
O |
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| Mortensen |
Preben B |
PB |
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| Nelson |
Elliot C |
EC |
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| Nievergelt |
Caroline M |
CM |
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| Nordentoft |
Merete |
M |
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| Norman |
Sonya B |
SB |
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| O'Donnell |
Meaghan |
M |
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| Orcutt |
Holly K |
HK |
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| Panizzon |
Matthew S |
MS |
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| Peters |
Edward S |
ES |
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| Peterson |
Alan L |
AL |
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| Peverill |
Matthew |
M |
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| Pietrzak |
Robert H |
RH |
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| Polusny |
Melissa A |
MA |
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| Qin |
Xue-Jun |
XJ |
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| Ratanatharathorn |
Andrew |
A |
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| Ressler |
Kerry J |
KJ |
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| Rice |
John P |
JP |
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| Risbrough |
Victoria B |
VB |
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| Roberts |
Andrea L |
AL |
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| Rothbaum |
Alex O |
AO |
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| Rothbaum |
Barbara O |
BO |
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| Roy-Byrne |
Peter |
P |
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| Ruggiero |
Ken |
K |
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| Rung |
Ariane |
A |
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| Rutten |
Bart P F |
BPF |
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| Saccone |
Nancy L |
NL |
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| Sanchez |
Sixto E |
SE |
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| Schijven |
Dick |
D |
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| Seedat |
Soraya |
S |
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| Seligowski |
Antonia V |
AV |
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| Seng |
Julia S |
JS |
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| Sheerin |
Christina M |
CM |
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| Silove |
Derrick |
D |
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| Smith |
Alicia K |
AK |
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| Smoller |
Jordan W |
JW |
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| Sponheim |
Scott R |
SR |
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| Stein |
Dan J |
DJ |
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| Stein |
Murray B |
MB |
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| Stevens |
Jennifer S |
JS |
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| Teicher |
Martin H |
MH |
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| Thompson |
Wesley K |
WK |
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| Torres |
Katy |
K |
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| Trapido |
Edward |
E |
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| Uddin |
Monica |
M |
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| Ursano |
Robert J |
RJ |
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| Heuvel |
Leigh Luella van den |
LLVD |
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| Hooff |
Miranda van |
MV |
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| Vermetten |
Eric |
E |
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| Vinkers |
Christiaan H |
CH |
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| Voisey |
Joanne |
J |
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| Wang |
Yunpeng |
Y |
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| Wang |
Zhewu |
Z |
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| Werge |
Thomas |
T |
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| Williams |
Michelle A |
MA |
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| Williamson |
Douglas E |
DE |
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| Winternitz |
Sherry |
S |
|
| Wolf |
Christiane |
C |
|
| Wolf |
Erika J |
EJ |
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| Wolff |
Jonathan D |
JD |
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| Yehuda |
Rachel |
R |
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| Young |
Keith A |
KA |
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| McD Young |
Ross |
R |
|
| Zhao |
Hongyu |
H |
|
| Zoellner |
Lori A |
LA |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: Sleep |
| ISOABBREVIATION: Sleep |
| YEAR: 2019 |
| MONTH: Dec |
| DAY: 05 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1550-9109 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Sleep |
| COUNTRY: United States |
| ISSNLINKING: 0161-8105 |
| NLMUNIQUEID: 7809084 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| LDSC |
| LDSR |
| endelian randomization |
| genetic correlation |
| genetics |
| insomnia |
| posttraumatic stress disorder |
| sleep and psychiatric conditions |
| sleep disorders |
| sleep duration |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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